The Myths Associated with Cholesterol and their Facts

The Cholesterol Paradox Blog

American children and adults with high cholesterol average about 7% and 21%, respectively. Having no symptoms, high cholesterol can be challenging to detect without blood work, yet the hazards are real. It has been discussed in the previous blogs that having high cholesterol along with other risk factors can raise your chance of developing heart disease. It is also necessary for your body to make vitamin D, digest food, absorb vital minerals, and more (1). 

Even though most people are aware of cholesterol, there are still a lot of misconceptions about it. Don’t worry because we are here to correct your misconceptions. This post has reviewed the most recent findings and information regarding cholesterol. This blog will clear your queries regarding cholesterol.

Myth

High Cholesterol Food is always responsible for Cardiovascular Complications

Fact

Diet culture frequently blames food, glorifying some foods while demonizing others. Numerous foods high in fatty acids and related to heart disease include red meats, dairy products, and other foods that are also high in cholesterol. According to recent studies, foods with high cholesterol but low-fat content, such as eggs and shrimp, do not cause heart disease. The discussion of cholesterol is further complicated by the identical structural characteristics of ingested cholesterol and cholesterol produced by the liver.

The cholesterol in meals is comparable to the cholesterol our bodies manufacture. Plants cannot synthesize it; hence it can only be found in animal products. Even though we can absorb cholesterol through the digestive system, only around 10% of dietary cholesterol affects our blood. Any food that contains calories, such as foods high in protein, carbs, fats, or alcohol, causes the liver to make the cholesterol found in our blood. Triglycerides, the primary fat found in our food and bodies, is also bundled with protein to form cholesterol.

Your body is remarkably adept at self-regulating: When you consume less dietary cholesterol, your body produces more to make the difference. Your body produces less cholesterol naturally when you consume more of it. Additionally, dietary cholesterol doesn’t appear to raise people’s risk of heart disease, even though it may slightly raise LDL in some individuals (2).

Myth

The sole source of cholesterol is our diet

Fact

While animal commodities, such as meat, fish, eggs, and whole milk, can contain cholesterol, your liver also naturally manufactures cholesterol. Some individuals produce more cholesterol in their livers than they require due to certain reasons such as genetics or any other disease. High cholesterol is possible in certain circumstances, but a balanced diet and careful management prevent it (3).

You may wonder if cholesterol is obtained only from animal sources, then vegans do not have any chance of having high cholesterol. You can be wrong here. The fact is that a vegan has the same chance of developing high cholesterol as a person who eats meat. This is because the real cause of health issues is inflammation caused by high carbohydrate consumption.

Myth

Only egg whites have benefits, and yolks are not our good folks

Fact

According to Stewart, “Natural and farm eggs are a high protein supply and rich in a variety of vitamins and minerals.” Egg white provides some protein (about two grams). Most of an egg’s iron, biotin, folate, and vitamins A, D, E, and K are found in the egg yolk, along with around four grams of protein.

One ground-breaking 2013 study examined the effects of consuming whole eggs vs. an equivalent amount of a yolk-free egg substitute on blood cholesterol. Three months later, those who consumed three whole eggs daily had higher HDL levels and lower LDL levels than those who used egg substitutes.

You don’t have to avoid eggs as long as you consume them in moderation (4). The American Heart Association advises a daily intake of no more than 300 mg of dietary cholesterol.  Up to 200 mg, or more than two-thirds of the advised amount, can be found in eggs. As a quick reminder, your body is working for you.  The cholesterol level in your bloodstream is constrained if your nutritional intake increases since your body create less cholesterol.

Myth

All types of cholesterol are harmful to our body

Fact

Although excessive cholesterol is frequently discussed, not all cholesterol is harmful, as discussed in detail in the previously published article. In fact, according to the CDC, your body needs it for several essential processes like creating hormones and cells. Even our liver produces some.

The majority of research currently demonstrates that for the majority of people, dietary cholesterol does not significantly affect blood cholesterol, contrary to what medical professionals traditionally believed. Our body produces and controls the amount of cholesterol needed to perform critical tasks like making hormones and serving as a crucial component of cell membranes,

Different varieties of cholesterol exist. Unfortunately, the majority of the cholesterol in your body is the “bad” type of cholesterol, low-density lipoprotein (LDL), as already discussed in previous articles of this series. LDL can adhere to the blood vessel walls. Heart disease and stroke risk may increase due to this plaque buildup.

Your blood also contains high-density lipoprotein (HDL), a “healthy” type of cholesterol. Cholesterol is taken up by HDL and sent to the liver for processing. Thus, your risk of heart disease and stroke is decreased by HDL (5).

Myth

It would be best if you avoided cholesterol in your diet as much as you can

Fact

“The current nutrition guidelines no longer list dietary cholesterol as one of the “nutrients to limit.” The majority of the top-quality animal products are exceptionally nutrient-dense. You miss out on many health-promoting elements if you eliminate all or most dietary cholesterol. Blood cholesterol levels are not significantly affected by dietary cholesterol. Instead, it is more affected by the quantity and kind of fats you ingest. Consuming excessive amounts of trans and saturated fats will increase your cholesterol.

Eggs and shellfish, which are foods rich in dietary cholesterol, are excellent sources of lean protein and probably have less influence on cholesterol levels than many manufactured snack foods. For instance, grass-fed yogurt offers calcium and bacteria that help the gut repair, as well as iron and B vitamins that are abundant in grass-fed cattle.

Foods containing some cholesterol shouldn’t be quickly condemned because only 10% of that dietary cholesterol affects our cholesterol. Saturated fats, primarily in animal products with high-fat content, should be avoided as much as possible. 

A complete 100% saturated fat compared to 10% dietary cholesterol can affect the liver’s ability to produce cholesterol. The American Heart Association (AHA) advises aiming for six percent or less of your daily caloric intake to come from sources of saturated fat, which include:

• butter
• cheese
• lard
• pork
• heavy cream
• skin-on poultry
• lamb
• beef

Myth

The products with a claim of being cholesterol free are healthy for us

Fact

This claim can be found in various products, including chocolate sandwich cookies and potato chips with cream filling. Food businesses frequently employ popular nutrition phrases to capture your interest and promote the consumption of the goods, with ‘cholesterol-free’ being one prominent example. Any meal that doesn’t include meat or dairy products with a lot of fat could be labeled as “cholesterol-free.” 

Do highly processed, nutrient-deficient foods suddenly qualify as healthy? 

Nope!

Aim to use various colors and plants in your dishes, along with some lean protein, healthy fats, and whole grains, rather than focusing on specific product promises. Another prevalent concept that must be addressed is that food that does not contain cholesterol is good for your heart. Even foods low in cholesterol or lacking in cholesterol may contain large amounts of saturated or trans fats, increasing your cholesterol levels.

Myth

Exercise and diet are enough to lower my cholesterol level in whichever state I am  

Fact

Exercise and diet should be adopted in the first place and must be included in your daily routine. Despite the importance of diet and exercise, many people still require medicine. You may require cholesterol medications known as statins if you have type 2 diabetes, heart disease, a family history of high cholesterol, or any of these conditions (6).

Myth

Only overweight people have high cholesterol 

Fact

Any person, irrespective of his weight, can have high cholesterol. High cholesterol can affect anyone, whether lean or overweight, while overweight people are more prone to have it. Adults of all ages require routine cholesterol testing. According to the American Heart Association, everyone over 20 should get their cholesterol levels examined every four to six years.

Myth

High cholesterol is not bad for kids but only for adults

Fact

Children with familial hypercholesterolemia, an inherited form of elevated cholesterol, are at an increased risk of developing heart disease. Ask your pediatrician whether you ought to have your child’s cholesterol checked. Additionally, all children can profit from a head start on a healthy diet and way of life, lowering the chance of developing heart issues.

Myth

The cereals such as OATS, high in fiber, are an excellent source to reduce cholesterol levels

Fact

According to research, oatmeal contains many fibers and can only help decrease cholesterol.  The appropriate kinds of fats and fiber may have a more significant impact. The first dietary modification advised to lower cholesterol is reducing your intake of incredibly saturated fats.

Myth

The only way to lower cholesterol is by taking medicine

Fact

Maintaining healthy cholesterol levels requires leading a healthy lifestyle. Increased physical activity, a nutritious diet rich in fresh fruits and vegetables, and giving up smoking can all help lower cholesterol levels in people who already have high cholesterol or are at risk of getting it. However, some people’s high cholesterol will persist despite any lifestyle modifications they make.  A doctor may recommend cholesterol-lowering drugs in these circumstances.

Myth

Women have low chances of heart disease than men

Fact

Both sexes have comparable rates of high cholesterol. Therefore, heart disease should be a worry for everyone. The Statistics show that heart disease is the leading cause of mortality for American women, killing one in five. Knowing the symptoms is important because women’s heart disease might manifest differently (7).

References

1.        Ravnskov, U. Cholesterol Myths. (New Trends Publishing, Incorporated, 2003).

2.        Vomero, J., Center, H. & Vomero, C. D. J. Cholesterol Myths–Is Cholesterol Really That Bad?

3.        Ma, H. & Shieh, K.-J. Cholesterol and human health. J. Am. Sci. 2, 46–50 (2006).

4.        Dawber, T. R., Nickerson, R. J., Brand, F. N. & Pool, J. Eggs, serum cholesterol, and coronary heart disease. Am. J.   Clin. Nutr. 36, 617–625 (1982).

5.        Wald, N. J. & Law, M. R. Serum cholesterol and ischaemic heart disease. Atherosclerosis 118, S1–S5 (1995).

6.        Mattson, F. H., Erickson, B. A. & Kligman, A. M. Effect of dietary cholesterol on serum cholesterol in man. Am. J. Clin.               Nutr. 25, 589–594 (1972).

7.        Kromhout, D. Body weight, diet, and serum cholesterol in 871 middle-aged men during 10 years of follow-up (the                       Zutphen Study). Am. J. Clin. Nutr. 38, 591–598 (1983).

The Culprits of High Cholesterol

The Cholesterol Paradox Blog

In our previous blogs, we have discussed cholesterol, its types, symptoms of high cholesterol, the impact of cholesterol on the cardiovascular system, and other factors. But what is the real cause of high cholesterol levels in the human blood?

High cholesterol in your body can be caused by various reasons, including underlying medical conditions such as high blood pressure and diabetes, as well as lifestyle choices like smoking, eating poorly, and not exercising, and some other factors, details of which you will find in the following text. So, let’s dig into the article and discuss the real culprits of high cholesterol in the blood. 

Risk factors of high cholesterol

Your risk of high blood cholesterol may grow due to your lifestyle. It could involve lousy eating habits, a lack of exercise or other physical activity, obesity, excessive alcohol consumption, smoking, etc.

Although some foods, including eggs, liver, and kidneys, contain dietary cholesterol. This has no impact on blood cholesterol levels. It would help if you kept an eye on the amount of saturated fat in your diet. 

Sedentary lifestyle

Your LDL cholesterol level may rise if you lead a sedentary lifestyle. If you are obese, you probably have lower HDL cholesterol and triglycerides and greater LDL cholesterol levels. Sitting for long periods is unhealthy, whether you’re doing it at a desk or on a couch. It has been connected to heart attacks, stroke, high cholesterol, and obesity. 

An enzyme that transforms LDL cholesterol (bad cholesterol) into beneficial HDL cholesterol decreases by 95% when sitting for an extended period. Take frequent breaks to safeguard your heart. If possible, take a 5-minute stroll every hour while standing up at least once every 30 minutes.

Alcohol

Regularly consuming a lot of alcohol might raise your triglyceride and cholesterol levels. Your liver processes alcohol in addition to digesting cholesterol. Thus, drinking too much can have an impact on your cholesterol. 

Compared to men who don’t drink much, men who do tend to have higher cholesterol levels. Even for individuals who only occasionally drink, it is true. If you drink alcohol, limit your intake to no more than one for women and two for men each day.

Smoking

Smoking has effects on more than just your lungs. It can make you more susceptible to cardiovascular diseases, stroke, high blood cholesterol, and other heart-related conditions. A substance in tobacco known as acrolein prevents “good cholesterol” (HDL) from transferring cholesterol to the liver, which results in cholesterol plaques (atherosclerosis). This suggests that smoking promotes LDL buildup and reduces HDL cholesterol’s capacity to repair LDL damage (1).

Poor diet

Diet plays a very important role in our overall health. Overeating saturated or trans fats are unhealthy and can lead to high cholesterol levels. Saturated fats are usually present in fatty cuts of meat and full-fat dairy products. Trans fats are found in desserts or packaged snacks.

According to the CDC (Centers for Disease Control and Prevention), high cholesterol meals increase the risk of heart attack and stroke. However, recent studies have provided more context for discussing heart disease and dietary cholesterol. Heart disease is caused by various variables, such as heredity, chronic inflammation, hypertension, and smoking tobacco. 

Obesity

A person is said to have obesity if he or she has a body mass index (BMI) of 30 or greater. Unhealthy lifestyles cause many health problems. Obesity is one of them. It raises your risk of high blood cholesterol. Lack of physical exercise and poor eating habits may lead to obesity.

Age

Unhealthy cholesterol doesn’t need to be present only in older people. High levels of cholesterol can affect people of all ages. Even young children can have high cholesterol. However, high cholesterol is mainly diagnosed in people between 40 and 59. With the increase in age, the body’s metabolism changes. The liver becomes unable to remove LDL cholesterol. These changes may lead to an increased risk of developing high blood cholesterol.

Risk factors as causes or correlations of high cholesterol

All the risk factors explained above can contribute to high cholesterol. They are correlated with high cholesterol, but they cannot be considered the causes of high cholesterol. If you are otherwise healthy, you can avoid your risk of high cholesterol by adopting a healthy lifestyle, quitting smoking or alcohol, and exercising regularly.

Causes of high cholesterol

The following can be considered as the causes of high cholesterol. It does not mean that you will have high cholesterol if you have any of the following problems. Even if there is a family history of high cholesterol, you can still protect yourself from unhealthy cholesterol levels with a heart-healthy lifestyle. If you adopt healthy habits for the heart in childhood and continue throughout your life, you can prevent harmful blood cholesterol and heart diseases.

Underlying health issues

High cholesterol is frequently present in people with diabetes and high blood pressure (hypertension). The following medical disorders can also result in elevated cholesterol levels.

• Kidney disease
• Liver dysfunction
• Pregnancy
• Menopause
• Hypothyroidism

Medications

Some health problems may not themselves raise cholesterol levels. Still, the medicines you take for those problems can increase your level of LDL cholesterol or lower your level of HDL cholesterol.

• Arrhythmia medicines such as amiodarone
• Beta-blockers for treating angina, chest pain, or high blood pressure
• Chemotherapy medicines for cancer
• Diuretics such as thiazide used to treat high blood pressure
• Immunosuppressive medicines that are used to treat inflammatory diseases or to prevent rejection after organ transplant
• Retinoids used to treat acne
• Steroids such as prednisone used for inflammatory diseases such as lupus, rheumatoid arthritis, and psoriasis.

Any medicine you take should be discussed with your doctor. You could require a different dosage or alternative medicine.

Stress 

Everyone occasionally experiences stress from their job, finances, families, or having to deal with a significant life transition like moving (2). Are stress and high cholesterol related? In a single word, yes. 

Long-term stress can increase your risk of high cholesterol and perhaps heart disease. You’re you are stressed, your body may raise levels of certain hormones such as corticosteroids. These hormones can cause your body to make more cholesterol. However, you may take action to manage your stress and safeguard your heart.

Mild stress causes your body to release cortisol and adrenaline hormones, which energize your heart, sharpen your mind, and aid problem-solving. Stress may benefit you if it encourages you to concentrate and work harder to conquer an issue in your life.

The problem arises with chronic stress. Your stress hormones remain high if it lasts for a long time and is continuous, putting dangerous pressure on your heart and other organs. 

Chronic or prolonged stress can raise blood cholesterol levels and increase the risk of heart disease due to elevated cortisol levels. Excess LDL or “bad” cholesterol can accumulate over time in your arteries, hardening and clogging them. Additionally, stress causes inflammation, which lowers HDL, or “good,” cholesterol, further causing a decrease in clearance of additional LDL. 

The common ways people deal with stress also play a role in the relationship between stress and cholesterol. In difficult times, you may eat poorly and put on weight, smoke, consume excessive amounts of alcohol, or invest extra time on the sofa than working out. These all increase your risk of having high cholesterol (3).

Sex

Evidence suggests that between the ages of 20 and 39, men are at greater risk of developing high cholesterol than women. Female hormones such as estrogen and testosterone are protective against high blood cholesterol. Women’s risk goes up after menopause.

Family history

Family members often have similar cholesterol levels. It suggests that genetics has a role to play in it. Your genes can increase your risk of high cholesterol levels. Changes in genes or mutations can be passed from parents to children, which can cause a condition called familial hypercholesterolemia. It is the medical term for high cholesterol that runs in families. It is a rare disease, but if left untreated, it can worsen over time. High cholesterol is present from birth in people with familial hypercholesterolemia, which can cause the early onset of cardiac conditions such as atherosclerosis and other cardiovascular diseases.

A child, sibling, or brother of someone with familial hypercholesterolemia has a 50% chance of developing the illness. If there is a history of high blood cholesterol in your family, it may be difficult for your body to eliminate LDL cholesterol by breaking it down in the liver.

How to detect high cholesterol in the blood

A blood test (lipoprotein panel) is recommended to detect high cholesterol. Before your cholesterol test, you might need to fast (without food or liquids) for nine to twelve hours. Because of this, testing is frequently conducted in the morning. Your healthcare professional will tell you in detail if there are any other particular instructions.

The cholesterol test measures cholesterol in milligrams per deciliter (mg/dl). The cholesterol test includes the following numbers.

• Total cholesterol
• HDL levels
• VLDL levels and triglycerides
• LDL levels
• Non-HDL cholesterol
• The ratio between cholesterol and HDL

The term “advanced lipoprotein analysis” refers to a blood sample that goes beyond routine cholesterol testing. Instead of measuring cholesterol to determine the number of lipoproteins (also known as “lipid-carrying proteins”), it measures the lipoproteins that directly contribute to heart disease (4).

References

1. Katcher, H. I., Hill, A. M., Lanford, J. L. G., Yoo, J. S. & Kris-Etherton, P. M. Lifestyle approaches and dietary strategies to lower LDL-cholesterol and triglycerides and raise HDL-cholesterol. Endocrinol. Metab. Clin. North Am. 38, 45–78 (2009).
2. Weissglas-Volkov, D. & Pajukanta, P. Genetic causes of high and low serum HDL-cholesterol. J. Lipid Res. 51, 2032–2057 (2010).
3. Troxler, R. G. & Schwertner, H. A. Cholesterol, stress, lifestyle, and coronary heart disease. Aviat. Space. Environ. Med. (1985).
4. Artiss, J. D. & Zak, B. Measurement of cholesterol concentration. Handb. lipoprotein Test. 2, 189–205 (1997).

Role of Cholesterol in Cardiovascular Diseases

The Cholesterol Paradox Blog

Cholesterol is the most despised, misunderstood, and contentious substance in our body and our diet. Particularly new and recent cholesterol standards have generated media attention and heated medical debate concerning cholesterol’s involvement in heart disease.

The lipoproteins that transport cholesterol to and from cells are the real culprits when cholesterol is linked to cardiovascular diseases, not the lipid itself. The lipoproteins can roughly be split into two groups.: low-density lipoprotein (LDL), also known as bad cholesterol, which clogs arteries and raises the risk of heart attacks, and high-density lipoprotein (HDL), also known as good cholesterol. 

US physician John Gofman made this distinction in the 1950s. His research into the blood plasma of those with heart attacks revealed significant increases in LDL levels while HDL 

Fig1 Cardiovascular system of human body

levels were below average. In 1984, a trial involving about 3,800 patients discovered that individuals with decreased levels of LDL had a lower probability of experiencing a heart attack or needing bypass surgery. This finding helped the cholesterol theory acquire general acceptance (1).

What happens when cholesterol level increases

Because high cholesterol does not create any symptoms, many people have no idea whether their cholesterol values are abnormally high or not. As a result, it’s critical to learn about your cholesterol levels.

A screening test is a single way to determine if you have a higher LDL cholesterol level. Untreated cholesterol can cause plaque to accumulate in your arteries over time which is called atherosclerosis. This condition increases your chance of having a heart attack or stroke. Watch out for signs of a heart attack or an impending stroke, such as:

 

• Extreme fatigue                                                 
• Numbness
• Chest pain or angina                                         
• Numbness or coldness in extremities
• Nausea
• Slurred speech
• Shortness of breath
• High blood pressure

Do not delay visiting the closest 24-hour emergency room if you have any worries about the symptoms you are feeling.

                                      Fig 2 Comparison of healthy heart and heart with decrease blood supply    

                                    

What are the contributing factors that cause increased cholesterol level

The rise in your blood cholesterol level may not be due to your dietary habits but to other contributing factors. The following health problems can lead to high cholesterol levels: 

• HIV/AIDS
• Chronic renal disease
• Hypothyroidism
• Lupus erythematosus
• Diabetes

Some prescription drugs for disease conditions may also cause a rise in your blood cholesterol level. Medications for acne, cancer, high blood pressure, HIV/AIDS, irregular heartbeats, and organ transplants are thought to increase cholesterol levels.

These factors alter cholesterol metabolism and reduce its clearance from the body. Cholesterol does not get converted to substances that are useful for our bodies. Instead, it gets converted into harmful fats and substances.

Impact of High-density lipoprotein on Cardiovascular System

HDL, sometimes known as “good” cholesterol, collects and transports it back to the liver. After breaking it down, the liver removes the cholesterol from the body. High HDL cholesterol levels can decrease your chances of heart disease and stroke. Individuals with greater HDL cholesterol levels are less likely to get a heart attack or stroke. 

It’s less confident that this advantage applies to those who raise their HDL levels through medication. The risk of heart attacks has been proven to decrease with lifestyle changes known to enhance HDL, such as stopping smoking, exercising, or modifying your diet. However, drugs that particularly boost HDL levels haven’t been able to lower the frequency of heart attacks. Surprisingly, those who naturally have HDL levels above 100 mg/dL (2.5 mmol/L) tend to be more susceptible to heart disease. Genetic factors might be to blame for this (2).

Impact of Low-Density Lipoprotein on Cardiovascular System 

Studies have shown that elevated low-density Lipoproteins (LDL), an important cholesterol marker, can indicate a higher risk of heart attack and CVD. 

Assessing oxidized low-density lipoproteins (OxLDL) levels, which are easily detected with a blood test, might give individuals who otherwise seem healthy an early signal of impending cardiac hazard. Studies show a 3.5-fold increased risk of developing metabolic syndrome in people with high levels of OxLDL over the next five years. High OxLDL levels are associated with a four times greater risk of developing heart disease in middle-aged, healthy men.

High cholesterol has been associated with an increased risk of cardiovascular complications. These include peripheral vascular disease, coronary heart disease, and stroke. Diabetes and hypertension are also associated with high cholesterol. 

The primary factor in each case is elevated cholesterol, which causes fatty acid plaques to accumulate in vessels across the body. Over time, these deposits thicken and restrict the amount of blood that can pass through your arteries. 

Erectile dysfunction and cholesterol

When a guy struggles to get or keep an erection during sex, it is known as erectile dysfunction. Long-term high cholesterol levels appear to cause the smaller blood arteries of the penis to constrict instead of expanding to accommodate increased blood flow during an erection (endothelial dysfunction). 

Additionally, when LDL cholesterol levels are too high, they can accumulate in the arteries. It combines with other chemicals to produce plaque, which stiffens and narrows additional blood vessels (atherosclerosis). Insufficient blood can flow to the heart and genitals as a result, which can cause erectile dysfunction (3).

Cholesterol and metabolic syndrome

Metabolic syndrome consists of a group of diseases. It includes the presence of a cluster of risk factors such as abdominal obesity, high blood pressure, impaired fasting blood glucose, high triglycerides, and low HDL cholesterol. The NHLBI (National Heart, Lung and Blood Institute) and AHA (American Heart Association) recommend that when one has 3 or more of these factors, he or she is said to have metabolic syndrome. Increased non-HDL cholesterol levels contribute to metabolic syndrome development (4). Metabolic syndrome affects health badly and increases the susceptibility to high blood pressure, diabetes, heart disease, and stroke (5).

Fig 3 Features of metabolic syndrome

Cholesterol and Diabetes

Diabetes is a chronic disease in which the body cannot utilize blood glucose properly. Hence, the blood sugar level increases, leading to various other health complications. Poor blood sugar control by the body can make cholesterol levels worse. The ratio of HDL (good cholesterol) to LDL (bad cholesterol) can be thrown off by diabetes. Diabetic patients frequently have LDL cholesterol that adheres to arteries and weakens blood vessel walls. A sugar called glucose binds to lipoproteins. Sugar-coated LDL lingers in the bloodstream longer and could contribute to plaque formation. 

Low HDL and high triglyceride levels, two different types of blood fat, are common in people with diabetes, particularly type 2 diabetes. These two factors raise the risk of arterial and heart disease. If a person has diabetes and low levels of good cholesterol but high levels of bad cholesterol and triglycerides, this condition is called diabetic dyslipidemia. It is estimated that up to 70% of people with type 2 diabetes have diabetic dyslipidemia.

Cholesterol and Stroke

Our brain needs enough blood to function properly. A stroke occurs when your brain does not get sufficient blood. In this condition, brain cells start dying. There are two types of stroke, including hemorrhagic and ischemic stroke. Cholesterol plaques may constrict some of the arteries leading to the brain. One could experience an ischemic stroke if a blood vessel supplying blood to the brain is entirely clogged (6). Hemorrhagic stroke occurs when a blood vessel providing blood to the brain ruptures.

Research showed that a higher level of LDL cholesterol is associated with an increased risk of ischemic stroke and HDL cholesterol has an inverse relation with ischemic stroke (7). In contrast, a higher level of LDL cholesterol seems to have a lower risk of hemorrhagic stroke, and HDL cholesterol appears to be positively associated with the risk of intracerebral hemorrhage (8).

Cholesterol and High Blood Pressure 

A complex association exists between high blood pressure and elevated cholesterol level. Doctors are still researching the relationship between high cholesterol and high blood pressure, generally known as hypertension. 

About 38% of all adults suffer from high cholesterol or a total cholesterol level of more than 200 mg/dL. Blood pressure issues affect more than 43% of people. Suppose your systolic reading is 140 or above. In that case, your diastolic reading must be 90 or greater to be considered high blood pressure. High cholesterol appears to produce inflammation and the production of specific hormones that stiffen or “constrict” arteries and hence increase blood pressure. 

When blood vessels act this way, doctors refer to it as “endothelial dysfunction.” Most persons with high blood pressure also have high cholesterol—more than 60%. Due to their status as cardiovascular disease risk factors, both pose a hazard to heart health. But you can manage all of your figures by following expert advice.

Cholesterol plaque can also manifest as symptoms in your legs and other parts of your body besides your brain and heart. The organs affected are the legs and feet. Hence, to have a healthy lifestyle, you should keep an eye on your symptoms and often get regular check-ups from your physician.

References

1. Saini, H. K., Arneja, A. S., & Dhalla, N. S. (2004). Role of cholesterol in cardiovascular dysfunction. The Canadian journal of cardiology, 20(3), 333–346.
2. Packard, C., Nunn, A., Hobbs, R., & Future Forum Editorial Board (2002). High density lipoprotein: guardian of the vascular system?. International journal of clinical practice, 56(10), 761–771.
3. Wei, M., Macera, C. A., Davis, D. R., Hornung, C. A., Nankin, H. R., & Blair, S. N. (1994). Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. American journal of epidemiology, 140(10), 930–937. https://doi.org/10.1093/oxfordjournals.aje.a117181
4. Khan, S. H., Asif, N., Ijaz, A., Manzoor, S. M., Niazi, N. K., & Fazal, N. (2018). Status of non-HDL-cholesterol and LDL-cholesterol among subjects with and without metabolic syndrome. JPMA. The Journal of the Pakistan Medical Association, 68(4), 554–558.
5. Kontopantelis, E., Springate, D. A., Reeves, D., Ashcroft, D. M., Rutter, M. K., Buchan, I., & Doran, T. (2015). Glucose, blood pressure and cholesterol levels and their relationships to clinical outcomes in type 2 diabetes: a retrospective cohort study. Diabetologia, 58(3), 505–518. https://doi.org/10.1007/s00125-014-3473-8
6. Tirschwell, D. L., Smith, N. L., Heckbert, S. R., Lemaitre, R. N., Longstreth, W. T., Jr, & Psaty, B. M. (2004). Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups. Neurology, 63(10), 1868–1875. https://doi.org/10.1212/01.wnl.0000144282.42222.da
7. Hackam, D. G., & Hegele, R. A. (2019). Cholesterol Lowering and Prevention of Stroke. Stroke, 50(2), 537–541. https://doi.org/10.1161/STROKEAHA.118.023167
8. Wang, X., Dong, Y., Qi, X., Huang, C., & Hou, L. (2013). Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke, 44(7), 1833–1839. https://doi.org/10.1161/STROKEAHA.113.001326

Relationship of Cholesterol and your health

The Cholesterol Paradox blog

Although you must have heard of cholesterol, you might not know what it is. So, before diving deep into the detailed discussion, let us clarify some aspects of cholesterol to you. For example, what exactly is cholesterol? What are its types? Why is it necessary for our life, and from where can you get it?

 

Cholesterol is a fat-like waxy substance carried in your bloodstream throughout the body. Our body is capable of synthesizing cholesterol naturally. It can also be obtained from the food you eat. The liver produces the majority of the cholesterol your body needs. Foods made from animal sources contain cholesterol. Cholesterol is an important structural element which makes up roughly 30% of cellular membranes. It serves to preserve the fluidity and structural rigidity of the membranes. Furthermore, it is also a precursor for producing steroidal hormones, vitamin D and bile acids in the body. This article will cover all the types of cholesterol and its relation to heart diseases.

What is meant by good and bad cholesterol

Cholesterol and other fats circulate in your bloodstream on proteins called lipoproteins. The most commonly known lipoproteins that carry cholesterol throughout the body are low-density lipoproteins (LDL) and high-density lipoproteins (HDL). They are explained in the text below.

Low-density lipoproteins or bad cholesterol

Often described as LDL, low-density lipoproteins are referred to as bad cholesterol. This is because these are considered potential cause of heart disease. The optimum level of LDL safe for our body is less than 100 mg/dl. A level between 100-129 mg/dl is near or above normal. The level between 130-159 mg/dl is considered borderline high. You frequently hear about the need to lower cholesterol. This refers to lowering and maintaining LDL cholesterol. Because a high LDL level causes plaque to accumulate in your arteries, we will explain its phenomenon later.

High-density lipoproteins (HDL) or good cholesterol

High-density lipoproteins are also called ‘good cholesterol’ because it helps remove cholesterol from your arteries. HDL carries cholesterol from other parts of your body to the liver. The liver then eliminates this excessive cholesterol and protects your body from its harmful effects. Normal HDL levels are essential to protect you from heart disease. Your body’s desired level of HDL is 60 mg/dl. This level is considered to be protective against heart-associated complications (1). A level below 40 mg/dl in men and below 50 mg/dl in women is considered risky. Low HDL levels are a risk factor for heart disease in both men and women. So you must maintain your level to live a healthy life.

Very low-density lipoproteins (VLDL)

Often described as VLDL, very low-density lipoproteins carry triglycerides from all body parts instead of cholesterol and transport them to the liver for elimination. Triglycerides constitute the majority of the fat in your body. When you eat, your body converts excess calories into triglycerides which are then stored in fat cells. Later, hormones cause the release of triglycerides for energy between meals. If you eat more calories than your body requires, you may have high triglycerides. Hence, it is essential to have normal VLDL levels so that the excess triglycerides do not accumulate in your body. It isn’t easy to assess the VLDL. Triglycerides constitute almost half of VLDL. Hence you can calculate your VLDL level as a proportion of triglycerides.

How cholesterol and other lipids contribute to plaque formation and atherosclerosis?

You must know that low-density products usually float on the water’s surface. The same phenomenon applies to fats in our blood. As blood is thicker, it makes the process slow. The lipids do not disintegrate in blood, and those with low density start to leave the blood slowly and make deposits on the walls of capillaries by combining with other substances, which accumulate as part of an inflammatory reaction. These deposits gradually become larger, thus not only blocking blood flow but also causing blood vessels to narrow. The blood channels known as arteries transfer oxygen-rich blood from the heart to every organ in your body. The arteries become smaller due to lipid buildup on their inner surfaces. This accumulation of lipids on the inner side of arteries is called atherosclerosis. This narrowing of arteries leads to various complications. The most morbid among them is coronary artery disease.

Role of saturated fat in cholesterol production

Saturated fat is a type of dietary fat, but it is one of the unhealthy fats. Saturated fats are most often solid at room temperature. Your body requires healthy fats for energy and other functions. Excess saturated fat can cause cholesterol to accumulate in your arteries. They increase LDL cholesterol synthesis, which is known as bad cholesterol. Hence, they can lead to many health problems. So, it would be best if you tried to limit these in your diet. Saturated fats are mostly found in foods derived from animals, including cheese, meat, butter, and milk.

Cholesterol and coronary artery disease

The major factor for coronary artery disease is high cholesterol. Cholesterol accumulates in the walls of coronary arteries, ultimately causing localized constriction of vessels. This reduces blood flow to a section of the heart muscle supplied by constricted arteries. Furthermore, cholesterol plaques can separate and move into smaller arteries or capillaries, entirely or partially blocking the channel. Occasionally, inflammatory cells may also go to the site of fractured plaque, causing additional constriction. The decreased blood flow to the heart can lead to chest pain, also called angina. If the vessel becomes fully clogged, it can lead to a heart attack (2).

The global drive to reduce cholesterol through diet and medication has been unable to stop the global pandemic of coronary artery disease from spreading. It is explained below in the text.

Cholesterol hypothesis and the work of Ancel Keys

The cholesterol hypothesis states that cutting cholesterol content prevents cardiovascular disease. The work by Ancel Keys has also been based on the hypothesis that higher cholesterol levels are the major cause of heart disease. It was also referred to as the lipid hypothesis. The majority of the medical community agrees with the above concept due to a lot of evidence. At the same time, there are a lot of health professionals who argue about the validity of the concept. According to them, blood cholesterol level is not the only reason, and there is not sufficient evidence to prove the hypothesis of Ancel Keys. According to them, there are other factors which also contribute to heart diseases. This debate is termed the cholesterol paradox.

The Relationship between cholesterol and mortality has also been problematic, with several studies reporting an inverse association between cholesterol and mortality. The term cholesterol paradox was used when it was found that mortality remained high in patients with low cholesterol levels (3). This relation relates to the controversial concept of fats and heart disease. According to the disease control and prevention centres, it is also possible that persons with a family history of heart disease have shared settings that could raise their risk.

Cholesterol and heart disease

Although there is an agreed concept by the majority that the levels of cholesterol and the risk of heart disease are positively correlated, it is not always true. Recent studies have shown that cholesterol level may be one of the risk factors for heart disease but not the ultimate cause of it. Heart disease patients may not always have higher cholesterol than healthy people. Many other factors play a role in causing heart disease.

It would be best if you did not fear cholesterol as it is integral to our body structure. As explained above, it plays a role in membranes’ integrity and synthesizing hormones and bile acids. All these phenomena are crucial for our health and survival. But you should keep a check on your cholesterol levels. Eating a healthy diet and living a healthy lifestyle keep you away from many ailments. It is reasonable to assume that although cholesterol may influence health, health may also influence cholesterol.

Cholesterol-health Relationship

Cholesterol-health relationships may differ in subpopulations dependent on health status (7). While most of the time, it is thought that a higher cholesterol level in old age is a risk for many diseases. Recent studies have denied this concept. A study showed that increases in cholesterol over time have beneficial associations in some older adults (4). Another study showed that low cholesterol has also been associated with cancer risk. Population interventions to lower cholesterol could lead to an increased risk of cancer (5). Cell culture showed that cancerous cells secrete a factor that alters cholesterol metabolism (6).

Many factors can affect your cholesterol level. Smoking, alcohol intake, major and minor illnesses, hospitalization, heart attack, acquired immune deficiency syndrome (AIDS), weight change and selected medications are some factors that alter your cholesterol metabolism (8).

References

1. Barter, P., Gotto, A. M., LaRosa, J. C., Maroni, J., Szarek, M., Grundy, S. M., Kastelein, J. J., Bittner, V., Fruchart, J. C., & Treating to New Targets Investigators (2007). HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. The New England journal of medicine, 357(13), 1301–1310. https://doi.org/10.1056/NEJMoa064278
2. Grundy S. M. (1986). Cholesterol and coronary heart disease. A new era. JAMA, 256(20), 2849–2858.
3. Budzyński, J., Tojek, K., Wustrau, B., Czerniak, B., Winiarski, P., Korzycka-Wilińska, W., & Banaszkiewicz, Z. (2018). The “cholesterol paradox” among inpatients – retrospective analysis of medical documentation. Archives of medical sciences. Atherosclerotic diseases, 3, e46–e57. https://doi.org/10.5114/amsad.2018.74736
4. Karlamangla, A. S., Singer, B. H., Reuben, D. B., & Seeman, T. E. (2004). Increases in serum non-high-density lipoprotein cholesterol may be beneficial in some high-functioning older adults: MacArthur studies of successful aging. Journal of the American Geriatrics Society, 52(4), 487–494. https://doi.org/10.1111/j.1532-5415.2004.52152.x
5. Schatzkin, A., Hoover, R. N., Taylor, P. R., Ziegler, R. G., Carter, C. L., Larson, D. B., & Licitra, L. M. (1987). Serum cholesterol and cancer in the NHANES I epidemiologic followup study. National Health and Nutrition Examination Survey. Lancet (London, England), 2(8554), 298–301. https://doi.org/10.1016/s0140-6736(87)90890-7
6. Ueyama, Y., Matsuzawa, Y., Yamashita, S., Funahashi, T., Sakai, N., Nakamura, T., Kubo, M., & Tarui, S. (1990). Hypocholesterolaemic factor from gallbladder cancer cells. Lancet (London, England), 336(8717), 707–709. https://doi.org/10.1016/0140-6736(90)92204-u
7. Harris, T., Feldman, J. J., Kleinman, J. C., Ettinger, W. H., Jr, Makuc, D. M., & Schatzkin, A. G. (1992). The low cholesterol-mortality association in a national cohort. Journal of clinical epidemiology, 45(6), 595–601. https://doi.org/10.1016/0895-4356(92)90131-6
8. Jacobs, D., Blackburn, H., Higgins, M., Reed, D., Iso, H., McMillan, G., Neaton, J., Nelson, J., Potter, J., & Rifkind, B. (1992). Report of the Conference on Low Blood Cholesterol: Mortality Associations. Circulation, 86(3), 1046–1060. https://doi.org/10.1161/01.cir.86.3.1046
9. Glatz, J. F., & Katan, M. B. (1993). Dietary saturated fatty acids increase cholesterol synthesis and fecal steroid excretion in healthy men and women. European journal of clinical investigation, 23(10), 648–655. https://doi.org/10.1111/j.1365-2362.1993.tb00726.x

Strategies and Lifestyle habits to address the obesity problem

The Obesity Dilemma IV

 

The development of guidelines for obesity is complex. It involves both treatment interventions and interventions related to screening and prevention. Obesity is the most chronic metabolic disease worldwide. The WHO has already declared it a global epidemic. In the European region, obesity presents an unprecedented and underestimated public health challenge. Despite steady progress in managing obesity, the prevalence of obesity continues to rise, stressing the necessity for prevention strategies at the individual and community level. (2)

 

Comprehensive Obesity Management

The management and treatment of obesity include weight loss, risk reduction, and health improvement. It can be achieved by modest weight reduction (i-e 5-10% of initial body weight), improved nutritional content of the diet, and an increase in physical activity and fitness. (2)

 

Where someone with the risk of obesity should turn to for solutions

Setting the right eating habits is a basic pillar of the non-pharmacological treatment of obesity. (15) If you are susceptible to the risk of obesity, you can go to a dietitian, nutritionist, behavioral counselor, or an obesity specialist. They will help you understand and change your eating and activity habits. They will tell you your daily calorie requirement so that you can lose weight steadily. This will help you to make positive and healthy lifestyle changes.

 

The benefits of weight loss

Evidence suggests that the risks of mortality and morbidity associated with obesity can be reduced effectively with weight loss. (1) Weight loss results in a short-term decrease in blood pressure. (3) research has shown that a 5-10% weight loss of pretreatment body weight has been associated with significant improvements in medical disorders such as type 2 diabetes, hypertension, and cardiovascular disease. It also results in an increase in life span. (1)

 

Prevention of obesity

Adequate management of obesity is essential and requires the principles of integrated care for disease management. The standard principle of management is early detection, diagnosis, and treatment of obesity. The preferred treatment is a combined lifestyle intervention and, when appropriate, additional medical therapies. Individuals respond to local environmental factors like socio-cultural, economic, and physical environments. (5)

Figure1: Representation of environmental influences interacting with individuals and the effects on behavior and body weight

 

Biological and socioenvironmental (economics, culture, social networks, and physical environment) influences on behaviors such as eating and physical activity play a role in obesity prevention. (5)

 

Consulting with the GP to address the problem of obesity

If you notice a change in your body weight, you should consult with your GP. Your GP will guide you to overcome the problem of obesity.

 

Latest guidelines for obesity management

In 2013, the National Health and Medical Research Council (NHMRC) released updated clinical practice guidelines for the management of obesity in primary care. General Practitioners are encouraged to use the ‘5As’ to manage patients’ weight. These are Ask, Assess, Advise, Assist and Arrange. The new guidelines also follow a patient-centered approach, with the intention that the patient will be involved in the planning and implementation of their weight management. (9)

 

Socioeconomic Challenge of Obesity

Obesity prevalence is increasing at an alarming rate worldwide. Based on the existing prevalence and trend data, it is reasonable to describe obesity as a public health crisis. It affects people’s health and quality of life and adds to the healthcare budget. (5)

 

The economic cost of obesity

Given the high prevalence and the significant health risks associated with obesity, the economic costs of obesity have been estimated to be 3-8% of the total healthcare expenditure. Most of the cost arises from treating hypertension, coronary heart disease, and type 2 diabetes. The indirect cost is in terms of lost output in the economy due to sickness absence or premature death. (1)

 

Shifting the burden of obesity toward the poor

The prevalence of obesity is higher in low and middle-income countries. (5) Statistical analyses were carried out, and the relative annual change in weighted prevalence of obesity is higher for rural than urban women. The analyses show that increased per-capita GDP is associated with an increased prevalence of overweight and obesity in rural areas. (4)

 

Special concerns for low and middle-income countries

The patterns of change in dietary intake and energy expenditure are essential in the development of obesity. Fetal nutritional insufficiency triggers anatomical, hormonal, and physiological changes that enhance survival in a resource-poor environment. These adaptations may contribute to disease development with plentiful resources in the postnatal environment. Maternal exposure to famine conditions causes moderate to severe nutrition restriction during pregnancy. Studies show that there is a role of maternal micronutrient intake in epigenetic changes that affect child adiposity. There is also evidence that maternal overweight and obesity in pregnancy influence disease risk among offspring. (4)

 

Obesity and Genetics

The general public believes that body weight is within personal control. This concept worsens attitudes towards obese persons. New research findings illustrate that obesity has a significant genetic component. (6) This could increase awareness of an important uncontrollable element of obesity. This finding can reduce the obesity stigma among healthy-weight people.

 

Role of genes in obesity

Genetics plays a substantial role in the predisposition to obesity. It may contribute to up to 70% risk for the disease. Over a hundred genes and gene variants related to excess weight have been discovered, but genetic obesity does not always cause obesity development. There are complex interactions between genetic, behavioral, and environmental influences and resulting epigenetic changes. Monogenic obesity though rare, typically appears in early childhood.   Polygenic obesity is the most common and demonstrates the interplay between genes and the obesogenic environment. (7)

Figure 2: Determinants of positive energy balance and fat deposition with an indication of the sites of action of a genetic disposition

 

Evidence from genetic epidemiology

Research has shown that the prevalence of obesity (BMI 30) is twice as high in families of obese individuals than in the population at large. Moreover, the risk of extreme obesity (BMI 45) is about seven to eight times higher in families of extremely obese individuals. (8)

 

Genome-wide-scans for obesity-related phenotypes

Genome-wide scans can be used to detect chromosomal regions showing linkage with obesity. Genetic screening for obesity concentrates on identifying mutations in specific genes in persons who are severely obese, with the greatest success rates in cases with an early onset. (8)

Figure 3 Chromosomal location of obesity

 

Contribution of Ethnicity toward Perception of Obesity

Racial or ethnic composition is an important correlate of obesity risk. Environmental and social norms that operate within communities and ethnic groups play an essential role in the development of obesity. (10)

The reasons for ethnic variation in obesity are complex. They may include differences in cultural beliefs and practices, perceptions of media, sleep, physical activity, level of acculturation, and ethnicity-based differences in body image. (11)

 

Factors affecting ethnicity toward obesity

Cultural beliefs and practices may contribute to racial disparities in obesity. Different cultures have different parental perceptions about their children’s health status and behaviors. In some cultures, mothers may view thinness as a reflection of malnutrition and poor health. Culturally defined perceptions of body image influence parenting strategies regarding eating and physical activity habits. (11)

 

Personal Responsibility towards Obesity

The regulation of hunger and satiety is poor in today’s obesogenic environment. A variety of factors lead to the risk of arriving at a pathological state of obesity. Sedentariness, food culture impacting seasonal weight gain, poor sleep, stress, energy-dense foods, genetic factors, and certain medications increase the risk of weight gain and obesity. (12)

 

Conscious experience and appetite regulation

Our brain is the most complex organ responsible for generating conscious experience. Individuals are free to choose how much they want to weigh. Appetite sensations are generated by the subcortical areas such as the hypothalamus and area postrema. (12)

For some individuals, the drive to eat may be greater than the ability to manage this drive. This can and should be managed solely by individuals’ willpower. (12)

 

Measures for prevention of obesity

Optimizing nutrition and growth in infancy and establishing healthy lifestyles can help reduce the risk of obesity. Interventions targeting infant feeding, parenting styles, diet, and physical activity in preschool children can reduce obesity risk. Interactive programs in group settings are likely to engage families. These programs should meet the needs of families and children. Programs that are fun, interactive, and able to engage parents and children are likely to be successful. Interventions should begin in infancy and continue through preschool years for maximum chances of success. (13)

 

Why the strategies adopted by society have failed

Many challenges are encountered while implementing successful interventions on a large scale. These include a lack of resources, participation of parents in community-based programs, socioeconomic factors, and financial, time-related, and social costs. Additional cost related to buying healthier foods and adopting a healthier lifestyle is a big challenge. Understanding these problems would help implement interventions and increase their success chances. (13)

 

Cost-Effectiveness of considering a prevention approach

We can deal with the problem of obesity through different approaches. The prevention approach is better than reacting to the problem. It is cost-effective and a healthy approach. Obesity-related chronic conditions are preventable and should be amenable to prevention strategies and programs. (14) If the susceptible individuals follow the interventions and successfully prevent obesity, they will not have to go through expensive treatment options. It would not only be healthy for them but also would not burden the healthcare system.

 

Effect of Obesity on the Current Healthcare

Obese individuals often have preventable chronic conditions. The management and treatment of chronic conditions related to obesity require higher utilization of medical services. The higher utilization of services leads to largely preventable costs. Emphasis on health management for obese individuals targeting lifestyle behaviors and weight management can help reduce costs for the individual and Medicare. (14)

 

References

1. Labib, M. J. J. o. C. P. (2003). The investigation and management of obesity. 56(1), 17-25
2. Tsigos, C., Hainer, V., Basdevant, A., Finer, N., Fried, M., Mathus-Vliegen, E., . . . Schutz, Y. J. O. f. (2008). Management of obesity in adults: European clinical practice guidelines. 1(2), 106-116.
3. Aucott, L., Poobalan, A., Smith, W. C. S., Avenell, A., Jung, R., & Broom, J. (2005). Effects of weight loss in overweight/obese individuals and long-term hypertension outcomes: a systematic review. Hypertension, 45(6), 1035-1041.
4. Popkin, B. M., Adair, L. S., & Ng, S. W. (2012). Global nutrition transition and the pandemic of obesity in developing countries. Nutrition reviews, 70(1), 3–21. https://doi.org/10.1111/j.1753-4887.2011.00456.x
5. Seidell, J. C., & Halberstadt, J. (2015). The global burden of obesity and the challenges of prevention. Annals of nutrition & metabolism, 66 Suppl 2, 7–12. https://doi.org/10.1159/000375143
6. Lippa, N. C., & Sanderson, S. C. (2013). Impact of informing overweight individuals about the role of genetics in obesity: an online experimental study. Human Heredity, 75(2-4), 186–203. https://doi.org/10.1159/000353712
7. Golden, A., & Kessler, C. (2020). Obesity and genetics. Journal of the American Association of Nurse Practitioners, 32(7), 493-496.
8. Loos, R. J., & Bouchard, C. (2003). Obesity–is it a genetic disorder?. Journal of internal medicine, 254(5), 401-425.
9. Jansen, S., Desbrow, B., & Ball, L. (2015). Obesity management by general practitioners: the unavoidable necessity. Australian journal of primary health, 21(4), 366–368. https://doi.org/10.1071/PY15018
10. Kirby, J. B., Liang, L., Chen, H. J., & Wang, Y. (2012). Race, place, and obesity: the complex relationships among community racial/ethnic composition, individual race/ethnicity, and obesity in the United States. American journal of public health, 102(8), 1572-1578.
11. Peña, M. M., Dixon, B., & Taveras, E. M. (2012). Are you talking to ME? The importance of ethnicity and culture in childhood obesity prevention and management. Childhood obesity (Print), 8(1), 23–27. https://doi.org/10.1089/chi.2011.0109
12. Grannell, A., Fallon, F., Al-Najim, W., & le Roux, C. (2021). Obesity and responsibility: Is it time to rethink agency?. Obesity reviews: an official journal of the International Association for the Study of Obesity, 22(8), e13270. https://doi.org/10.1111/obr.13270
13. Lanigan J. (2018). Prevention of overweight and obesity in early life. The Proceedings of the Nutrition Society, 77(3), 247–256. https://doi.org/10.1017/S0029665118000411
14. Musich, S., MacLeod, S., Bhattarai, G. R., Wang, S. S., Hawkins, K., Bottone, F. G., Jr, & Yeh, C. S. (2016). The Impact of Obesity on Health Care Utilization and Expenditures in a Medicare Supplement Population. Gerontology & geriatric medicine, 2, 2333721415622004. https://doi.org/10.1177/2333721415622004
15. Sadílková, A., Čmerdová, K., & Hásková, A. (2020). Role of dietitian in obese patients care. Úloha nutričního terapeuta v péči o obézní. Casopis lekaru ceskych, 159(3-4), 131–135.

 

 

 

The Relationship Between Obesity and The Cardiovascular System

The Obesity Dilemma III

Obesity is becoming a global epidemic, and there has been a dramatic increase in obesity cases among children and adults in the past 10 years. Obesity is an independent risk factor for cardiovascular disease and is associated with an increased risk of mortality and morbidity. As adipose tissue accumulates in excess amounts, various adaptations occur in cardiac structure and function. On the whole, obesity is associated with various cardiac complications such as coronary heart disease, heart failure, and sudden death because of its impact on the cardiovascular system. (1)

 

 

Cardiovascular adaptations to obesity

Obesity causes an increase in circulating blood volume to meet the metabolic demands of the enlarged adipose and lean tissue. As a result, blood pressure is elevated, causing high rates of hypertension. The increased filling pressures and volumes increase cardiac workload predisposing obese individuals to an abnormal left ventricular geometry and remodelling. The left ventricle is dilated to accommodate the increased amount of blood. Left ventricular hypertrophy and dysfunction may develop to keep the wall stress normal. The left atrium is also influenced by obesity. Increased blood volume and abnormal left ventricular function may lead to left atrium enlargement, increasing the risk for heart failure and atrial fibrillation. The increased filling pressures in the right side of the heart may lead to mild increases in pulmonary artery systolic pressure. (2)

Cardiovascular impact of increased adipose tissue mass

In obesity, adipose tissue undergoes maladaptive expansion, which compromises its function. Initially, adipocyte hyperplasia occurs, followed by hypertrophy. Angiogenesis is impaired, which causes localized hypoxia and ischemic necrosis. A vicious cycle of inflammatory response occurs.

Adipokines: crossroads between obesity and CVD

Adipokine dysregulation is the prominent hallmark of dysfunctional adipose tissue. Adipokines are secreted by adipose tissue; some are obesity-related low-grade state of inflammation. The peripheral fat deposition has a favorable impact on CVD risk. (2)

Obesity and cardiovascular disease

Duration of obesity and CVD

Research has shown that the alteration of cardiac performance in obese patients with left ventricular enlargement and wall thickening is attributed to the duration of obesity. The authors concluded that the risk of all-cause mortality increased as the number of years lived with obesity increased, independent of current BMI and set of potential cofounders. For every 2 years additionally lived with obesity, the risk of CVD mortality increased by 7%. (3) Hence delaying the onset of obesity can lower the risk of future CVD.

Fat-but-fit paradigm and CVD

Fat-but-fit paradigm refers to those individuals who, despite being obese, have good cardiorespiratory fitness level. Physical activity and physical fitness are closely related to obesity. Research has concluded that being more active was related to a marked reduction in the risk of incident CVD and early mortality. Enough evidence supports that being physically active is related to a lower risk of CVD and longer life expectancy. This evidence applies to both healthy individuals as well as to patients with CVD. (3)

Fat-but-fit and CVD prognosis

Research has concluded that people who are obese but fit have a higher risk of CVD mortality than normal-weight and fit people. On the contrary, this risk is 50% lower than that observed in average weight and unfit people and also dramatically lower than the risk in obese and unfit people. (3) 

Figure 1 PATHOPHYSIOLOGY OF OBESITY CARDIOMYOPATHY- this diagram shows the central hemodynamic, cardiac structural abnormalities, and alterations in ventricular function that may occur in severely obese patients and predispose them to heart failure³

 

                                                             

This data support 2 public health messages.

• Improving cardiorespiratory fitness without a weight reduction might have long-term benefits.
• An obese person who is fit might have a lower risk of CVD mortality than an average-weight but an unfit person.

Hence physical activity and physical fitness counteract the adverse effects of obesity on the cardiovascular system of man.

Obesity and Hypertension

The mechanisms of obesity-related hypertension and obesity are complex and interdependent. The sympathetic nervous system plays an essential role in affecting renal and adrenal function. (5) The presence of obesity and hypertension in the same individual increases cardiovascular risk. (6)

Sympathetic nervous system and reflex

Obesity shows signs of adrenergic activation, such as increased norepinephrine value. Sympathetic nerve discharge and an increased spillover rate of norepinephrine, particularly at the kidney level, are evident in obese individuals. This is due to impaired arterial baroreceptor control of sympathetic nerve activity. Increased sympathetic outflow to the kidney causes increased renal tubular sodium reabsorption, resulting in increased blood pressure. (5)

Adipokines

Leptin and adiponectin are the most critical products of fatty tissue, which play a role in blood pressure control through the regulation of arterial tone. Leptin reduces appetite and increases energy expenditure by stimulation of nervous system receptors. Levels of these adipokines are reduced in obesity. (5)

Studies have shown that central obesity measured by waist circumference is more closely related to the hypertension phenotype. (6)

Vascular alterations

Obesity and hypertensive state are associated with large artery structure and function alterations. An increase in arterial stiffness and a reduction in arterial compliance and distensibility occurs. (5)

Obesity and vascular dysfunction

Obesity affects the vascular system by altering the function of perivascular adipose tissue (PVAT). The primary role of the cardiovascular system is to transport oxygen and nutrients to organs, tissues, and cells. Dysregulation of the vascular system may result in increased peripheral vascular resistance and blood pressure. Also, vascular dysfunction promotes atherogenesis and increases insulin resistance. (7)

Role of perivascular adipose tissue

Perivascular adipose tissue surrounds large arteries, veins, small vessels, and skeletal muscle microvessels. PVAT plays a role in intravascular thermoregulation. It regulates vascular tone by releasing bioactive molecules, including adipokines, cytokines, and some gaseous molecules. (7)

Obesity has numerous adverse effects on cardiovascular structure and function. Abdominal adiposity is associated with vascular dysfunction. The PVAT mass and adipocyte size are increased, accompanied by other structural modifications in the PVAT. Its anticontractile effect is completely lost in obese patients.

Figure 2 MECHANISMS OF PVAT DYSFUNCTION IN DIET-INDUCED OBESITY⁷

 

(7) Based on research results, an ‘obesity triad’ consisting of PVAT hypoxia, inflammation, and oxidative stress can be proposed as the central mechanism in obesity-induced PVAT dysfunction. (7)

Obesity and atherosclerotic vascular disease

Obesity is a multifactorial and chronic disease in which visceral and subcutaneous fat accumulation occurs. Obesity is linked with atherosclerosis through various mechanisms, including abnormalities in lipid metabolism, insulin resistance, inflammation, endothelial dysfunction, and adipokine imbalance. (8)

Adipokine imbalance

Evidence suggests that an imbalance between pro-inflammatory and anti-inflammatory adipokines is responsible for developing endothelial dysfunction and atherosclerosis. (8)

Oxidative stress links obesity to atherosclerosis

Obesity increases systemic oxidative stress. It results from an imbalance between the production of free radicals and anti-oxidant systems. Increased oxidant production increases atherosclerosis susceptibility. (8) The lipid components of low-density lipoproteins (LDL) undergo oxidative modification. LDL deposits in the vascular wall early in the atherosclerotic lesion, where it is oxidized. Oxidized lipids contribute to many stages of atherosclerotic development. (9)

Endothelial dysfunction

Endothelium lines the entire vascular system. Endothelial dysfunction is known to be the earliest clinically detectable form of atherosclerosis. (10) Obesity impairs endothelial function through several mechanisms, including decreased NO production. (8)

Figure 3 ENDOTHELIAL DYSFUNCTION-A SYSTEMIC DISEASE. Figure represents risk factors and widespread systemic manifestations of vascular endothelial dysfunction

 

Heart failure and obesity

Obesity is a significant risk factor for the development of heart failure. Research showed that the risk of heart failure increased by 7% for women and 5% for men for each unit increase in BMI. (11)

Mechanism of obese heart failure with a preserved ejection fraction

Obesity is associated with an abundance of renal tubular sodium transporters, overproduction of aldosterone, and activation of the renin-angiotensin axis. It leads to increased sodium reabsorption and plasma volume expansion. Increased blood pressure and blood volume in obesity lead to structural and functional alterations that contribute to heart failure. (12)

Furthermore, in individuals with obesity, there is a disruption of metabolic homeostasis and excess nutrient supply to the heart. The degree of obesity and adipose tissue location play important roles in the pathophysiology of obese heart failure. Epicardial fat increases pericardial restraint and intracardiac filling pressures in obese individuals with heart failure. (12)

Figure 4 PATHOPHYSIOLOGY OF OBESITY CARDIOMYOPATH

Via the production and release of inflammatory cytokines, epicardial fat can cause microvascular dysfunction and fibrosis of the myocardium. Remodeling and myopathy of the left atrium often lead to the development of atrial fibrillation, which contributes to the pathogenesis of heart failure with preserved ejection fraction in obesity. (12)

Diet quality, energy balance, and obesity

Obesity is challenging to treat after it has developed. Growing evidence suggests that poor diet quality causes energy imbalance. Furthermore, diet quality influences metabolic risk and propensity toward abdominal adiposity. The primary prevention of weight gain is promising for individual patients and populations. Studies suggest no harm of whole-fat milk for obesity or cardiovascular disease. Children who drink low-fat milk habitually gain more weight, and those who drink whole-fat milk gain less weight over time. (4)

Figure 5 Diet quality, obesity and metabolic risk- a modern paradigm. Diet quality influences risk of adiposity through multiple pathways, including altering energy intake, energy expenditure, microbiome-host interactions, body fat composition and

 

Exercise to reduce body weight

Increasing daily energy expenditure to tip the energy balance is effective in the treatment of obesity. Energy expenditure can be increased by increasing physical activity. The processes that accelerate the breakdown of the body’s major energy stores (glycogen and triacylglycerols) contribute to energy expenditure leading to weight loss. Exercise speeds up this phenomenon through the stimulated secretion of hormones and changes in substrate concentrations that activate enzymes. (14)

Exercise type should be taken into account in the treatment of obesity. Endurance exercise is the most popular exercise for body weight loss. Achieving significant weight loss in obesity is only the half job. Weight regain is common, and even a mild degree of weight increase seems to reverse the benefits of weight loss. Studies have shown that interventions combining diet and exercise result in smaller weight regain. (14)

References

1. Poirier, P., Giles, T. D., Bray, G. A., Hong, Y., Stern, J. S., Pi-Sunyer, F. X., & Eckel, R. H. (2006). Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation, 113(6), 898-918.
2. Koliaki, C., Liatis, S., & Kokkinos, A. (2019). Obesity and cardiovascular disease: revisiting an old relationship. Metabolism: clinical and experimental, 92, 98–107. https://doi.org/10.1016/j.metabol.2018.10.011
3. Ortega, F. B., Lavie, C. J., & Blair, S. N. (2016). Obesity and cardiovascular disease. Circulation research, 118(11), 1752-1770.
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Metabolic Disease Related to Obesity

Obesity Dilemma Blog

The sedentary lifestyle and the prompt availability of cheap foods make obesity a significant concern in this modern world. Obesity is not a single problem but gives rise to several issues related to metabolic, inflammatory, and degenerative disorders. The most deadly consequence of obesity is the effect on the cardiovascular system, which leads to atherosclerotic cardiovascular disease (ASCVD). Other than atherosclerotic cardiovascular disease, the risk of many conditions related to kidney, joints, central nervous system, liver, type 2 diabetes, and certain cancers also increases. 

Kidney problems:

Obesity gives rise to many health problems. One of the alarming problems caused by being overweight is a kidney problem. Obesity can lead to the development of long-term abnormalities in the functioning of the kidneys leading to the condition called chronic kidney disease. People with overweight have high energy demands of the body. Due to this, the metabolic rate of the body increases. The increase in the body’s metabolic rate is followed by the increase in the pressure of fluid in the kidney. The continuous high pressure in the kidney, also known as high intraglomerular pressure, damages the kidney’s structure. When the load on the kidneys exceeds the organ’s capacity, damages occur, which in severe cases can cause life-threatening conditions.(1) The loss of protein in the urine increases among obese people. The loss of essential proteins in the urine also deprives the body of the crucial factors which play an essential role in body functioning and the defense system. Due to the low functioning of the kidney, the urine becomes acidic. The loss of ions like sodium and phosphate also increases, which changes the blood chemistry and compromises bone health. The greater amount of oxalate ions in the urine predisposes the body to risk of kidney stones. In the case of extreme high BMI, the filtration process in the kidney exceeds the safe limit and can lead to complications, including kidney-related cancers. Because in an obese person, the growth factors are also high, which can increase the cell turnover in the already compromised kidney leading to the development of tumor cells.(2) (1)  

Joint Problems:

Obesity is a significant risk factor for soft tissues and joint trauma—the whole weight of the body balances on the joints of the body. When the body’s weight increases, the load on the joints also increases. The joints affected mainly by the overweight carry the most weight of the body, like hip and knee joints. The one-kilogram increase in weight causes a four to six-kilogram increase in load on the joints. The sports injuries in obese people are higher than in non-obese people. The obese person is more liable to fractures, ligament tears, and various ankles, knee, and hip joint injuries. The risk of knee displacement increases with the increase in body weight. Obesity is the leading cause of the wear and tear problem of the joints, known as osteoarthritis.(3) The fat cells in the obese person continuously release the inflammatory mediators, which cause inflammation in the joints and cause extreme damage.

The extra weight can cause damage to the cartilage of the joints leading to the condition known as arthritis. Similarly, the risk of damage to the connective tissues also increases, leading to the condition known as tendonitis. In these conditions, the joints become extremely painful and inflamed. (3)

Brain Problems:

It is found that the blood flow to the brain decreases in an overweight person. The decrease in blood flow is caused by the high cholesterol level in the blood, narrowing the arteries supplying the body. The decreased blood flow to the brain compromises the brain’s functioning and leads to various brain problems related to obesity. The overweight person has more risk of depression, bipolar disease, and suicide. The problems related to the memories like dementia and Alzheimer’s disease also increase. A study proved that an obese person has less grey matter and white matter in the brain. The reduction in the matter is associated with decreased brain cognitive function. Overnutrition causes inflammation in the brain. The fat cells also release the inflammatory mediators, which cross the blood-brain barrier and increase the inflammatory process in the neurons known as neuroinflammation. The inflammation causes the degeneration of the neurons called neurodegeneration. The imbalance in the gut microorganisms also damages the cluster of neurons in the gut. As a result, systemic inflammation occurs and leads to severe brain conditions. The inflammation further reduces blood flow to the brain and deprives the brain of oxygen. Cell death occurs and causes irreversible damage to the brain. (4–6)

 

Fatty liver:

The liver is the body’s primary organ with a dual blood supply. The fats in the body break down to produce free fatty acids in the blood. The liver uptakes the fatty acids, and the metabolism of fatty acids occurs in the liver. In the case of overweight, the demand of the body increases. Fat cells release an extra amount of fatty acids. The fat cells release non-esterified free fatty acids, which disrupt the composition of the blood. The liver’s rate of fatty acid uptake exceeds the liver’s capacity for fatty acid metabolism. Due to this, the level of triglycerides in the liver increases, leading to a condition known as nonalcoholic fatty liver disease (NAFLD). The greater

Diabetes:

Obesity is the major risk factor for the development of diabetes. In an obese person, the circulating sugar level is higher than that of a non-obese person. The continuous high sugar level triggers the insulin from the pancreas. The continuous triggering of the pancreatic cells increases the organ’s cells in response to more demand. Ultimately, the cells die when the load on the pancreas exceeds the organs’ limit. This leads to the development of type I diabetes in an obese person—also, the risk of type II increases. During obesity, the fat cells in the body increase in size due to the fat accumulation in the fatty cells. The increase in fat concentration causes insulin resistance in the obese person causing type II diabetes. Thus, in addition to many problems, obesity is a significant contributor to the development of diabetes, also known as diabesity. (9)

Cancer:

Obesity increases the risk of many cancers in the body, including cancer of the esophagus, breast, whole gut, gallbladder, kidney, liver, thyroid, brain, and ovaries.

The release of many growth factors by the fat cells in the obese person is responsible for developing the tumor cells in the body. Also, the obese person has more hormones like sex and insulin-like growth hormone. The factors released from the fat cells and the greater amount of hormones in the body increase cell turnover and predispose the body to a greater risk of developing tumors and malignancies. (2)  

Figure 5 SHOWS THE ASSOCIATION BETWEEN OBESITY AND DIFFERENT KIND OF CANCERS

Atherosclerotic cardiovascular disease due to obesity (ASCVD)

In obesity, atherosclerotic cardiovascular disease follows by the main disposing factor called metabolic syndrome. In obesity, metabolic syndrome is the common feature that plots an area for the development of atherosclerotic cardiovascular disease (10). The metabolic syndrome is characterized by the

• Hypertension
• Increase waist circumference
• High triglycerides in the blood 
• Low Blood HDL
• High fasting blood sugar

The metabolic syndrome associated with obesity increases the risk of atherosclerotic cardiovascular disease by two times.

What is atherosclerosis?

Atherosclerosis is the condition in which the cavity of the blood vessels decreases with the deposition of fatty substances in the vessels’ inner lining. This leads to the thickening and hardening of the vessels. These fatty substances include fatty acids, cholesterol, and the wastes of the cellular products mixed with calcium and coagulation factors like fibrin. 

How does atherosclerosis affect the body?

Atherosclerosis affects the different arteries of the body, leading to the development of many cardiovascular system diseases(11)(12). The blood flow to the organ supplied by the atherosclerotic artery reduces, and the organ’s functioning is compromised. In severe cases, the artery blockage completely deprives the organs of the blood supply and leads to ischemia. The main organ affected by atherosclerosis is the heart. The heart is the body’s main organ supplying the whole body with blood. If the heart function is compromised, the entire body is affected

Change in fat composition of blood leading to fat deposition in the vessels

When someone suffers from obesity, the following change occur in the fat content of the blood

1. Increased total TAG
2. Increased very-low-density and low-density lipoproteins in the blood along with raised apolipoprotein B.
3. Decreased high-density lipoproteins in the blood

The level of triglycerides-rich lipoproteins in the blood increases, which is the major contributor to the development of fatty depositions in the blood vessels. In a case-control study, researchers found that low-density lipoproteins are the main culprit in forming fat deposits within the vessels and increase the risk of cardiovascular disease by 3-times. So, we can say that the risk of fat deposit formation within the vessels is directly related to the elevated level of low-density lipoproteins(13). 

Similarly, when the levels of the high-density lipoproteins in the blood decreases, the risk of forming fat deposits in the body increases. The low level of the high-density lipoproteins in the body increases apoprotein B, a precursor for these deposits in the vessels. As obesity reduces high-density lipoproteins, it indirectly acts as a risk factor for cardiovascular disease(14).

Increase in the blood coagulation factors

The production of several factors from fat cells in an obese individual disturbs the clot formation pathway. The fat cells produce the following factors;

• Plasminogen activator inhibitor-1 (PAI-1)
• Interleukin-6
• Tumor necrosis factor-a

All these products result in a hyperactive clot-forming mechanism in the blood by disturbing the inner surface of the blood vessels. Also, the levels of the procoagulant in the plasma of the obese person are higher compared to the non-obese person. The disruption of the clot formation process and the fibrinolytic abnormalities cause the formation of many thrombi in the blood vessels and enhance endothelial dysfunction. The leptins produced by the fatty tissue further disrupt the hemostasis and enhance endothelial dysfunction. This condition is the leading factor contributing to developing chronic conditions of the vessels that cause cardiovascular disease and other vascular abnormalities (14)(15).

Increase in the inflammatory mediators

A proinflammatory phase exists in an obese individual due to the release of C-reactive protein from the abnormally deposited fat in the body responsible for the fat deposit formation in the vessels. The continuous lipid-induced injury followed by the proliferation of the smooth muscles and the macrophages promotes the thickening of the blood vessels (16).

References

1-Kovesdy C, Furth S, Zoccali C, Li PKT, Garcia-Garcia G, Benghanem-Gharbi M, et al. Obesity and kidney disease: Hidden consequences of the epidemic. Indian Journal of Nephrology [Internet]. 2017 Mar 1 [cited 2022 Jul 2];27(2):85. Available from: /pmc/articles/PMC5358165/

2-Henley SJ, Thomas CC, Lewis DR, Ward EM, Islami F, Wu M, et al. Annual report to the nation on the status of cancer, part II: Progress toward Healthy People 2020 objectives for 4 common cancers. Cancer. 2020 May 15;126(10):2250–66. 

3-Effect of Obesity on Your Bones and Joints | Ramsay Health UK [Internet]. [cited 2022 Jul 2]. Available from: https://www.ramsayhealth.co.uk/about/latest-news/effect-of-obesity-on-your-bones-and-joints

4-Gómez-Apo E, Mondragón-Maya A, Ferrari-Díaz M, Silva-Pereyra J. Structural Brain Changes Associated with Overweight and Obesity. J Obes [Internet]. 2021 [cited 2022 Jul 2];2021. Available from: https://pubmed.ncbi.nlm.nih.gov/34327017/

5-Ma Y, Ajnakina O, Steptoe A, Cadar D. Higher risk of dementia in English older individuals who are overweight or obese. International Journal of Epidemiology. 2020 Aug 1;49(4):1353–65.

6-Amen DG, Wu J, George N, Newberg A. Patterns of Regional Cerebral Blood Flow as a Function of Obesity in Adults. Journal of Alzheimer’s Disease. 2020;77(3):1331–7. 

7-Fabbrini E, Sullivan S, Klein S. Obesity and Nonalcoholic Fatty Liver Disease: Biochemical, Metabolic and Clinical Implications. Hepatology [Internet]. 2010 Feb [cited 2022 Jul 2];51(2):679. Available from: /pmc/articles/PMC3575093/

8-Fabbrini E, Sullivan S, Klein S. Obesity and Nonalcoholic Fatty Liver Disease: Biochemical, Metabolic and Clinical Implications. Hepatology [Internet]. 2010 Feb [cited 2022 Jul 2];51(2):679. Available from: /pmc/articles/PMC3575093/

9-Diabesity: How Obesity Is Related to Diabetes – Cleveland Clinic [Internet]. [cited 2022 Jul 2]. Available from: https://health.clevelandclinic.org/diabesity-the-connection-between-obesity-and-diabetes/

10-Obesity and Metabolic Syndrome [Internet]. [cited 2022 Jul 2]. Available from: https://www.news-medical.net/health/Obesity-and-metabolic-syndrome.aspx

11-Atherosclerosis – What Is Atherosclerosis? | NHLBI, NIH [Internet]. [cited 2022 Jul 2]. Available from: https://www.nhlbi.nih.gov/health/atherosclerosis

12-Atherosclerosis | Johns Hopkins Medicine [Internet]. [cited 2022 Jul 2]. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/atherosclerosis

13-Krauss RM. Dense low density lipoproteins and coronary artery disease. The American Journal of Cardiology. 1995 Feb 23;75(6):53B-57B. 

14-De Pergola G, Pannacciulli N. Coagulation and fibrinolysis abnormalities in obesity. Journal of Endocrinological Investigation 2002 25:10. 2014 Mar 11;25(10):899–904. 

15-Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003 Oct 1;42(7):1149–60. 

16-Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-Reactive Protein Levels in Overweight and Obese Adults. JAMA. 1999 Dec 8;282(22):2131–5.