8.2: Risk Factors

The main risk factors for atherosclerosis are genetic predisposition, high LDL-cholesterol, smoking, high blood pressure, and male gender. Diabetes also increases risk substantially. Obesity increases risk in several ways, including a higher risk of diabetes and high blood pressure, and a lower HDL-cholesterol.

High LDL-Cholesterol

As discussed in Chapter 7, LDL (low-density lipoprotein) carries cholesterol to various cells for use in making sex hormones, cell membranes, etc. LDL gets into the cells by attaching to LDL-receptors that protrude from the surface of the cell. When LDL locks into these receptors, the entire complex (LDL and its receptor) enters the cell, and the cholesterol is released inside. This reduces the amount of LDL in the blood and cuts back the cell’s own cholesterol production.

When LDL in the blood is excessive, LDL can deposit in the lining of the artery. Scavenger (clean-up) cells in the lining of the artery take in the LDL and release enzymes that cause local inflammation, contributing to the atherosclerotic process. LDL-cholesterol (the cholesterol carried in LDL) is called bad cholesterol, because the higher the LDL-cholesterol, the higher the risk of atherosclerosis.

HDL-cholesterol (the cholesterol in high-density lipoprotein) will be discussed later, but is mentioned here to contrast it to LDL-cholesterol. HDL generally takes up excess cholesterol and transports it to the liver, where it can be made into bile acids and secreted into the intestine to aid digestion (Chap. 6).

Most of the bile acids in the intestine are absorbed back into the blood, but some of it can get trapped by dietary fiber and excreted in the stool. Losing cholesterol via bile is about the only way the body gets rid of cholesterol. HDL-cholesterol is thus called good cholesterol.

It should be emphasized that the cholesterol itself is the same whether it’s carried in the blood by LDL (bad) or HDL (good).* People are often confused into thinking that there are two kinds of cholesterol in the diet—good cholesterol and bad cholesterol. In food, cholesterol is simply cholesterol.

^{*To remember which is bad or good, think of LDL as Lousy (high blood-levels raise the risk of heart disease) and HDL as Healthy (high levels protect), though some people have a genetic mutation that doesn’t let HDL to do its job.}

Genetic Predisposition

A family history of a heart attack or stroke—especially in a parent or sibling before age 55—suggests a genetic susceptibility. But keep in mind that families not only share genes, but often share eating, smoking, drinking, and exercise habits.

A very severe genetic defect is seen in the disease familial hypercholesterolemia [familial (inherited) hyper- (excessive) -emia (in the blood)]. Due to a defect in the gene for LDL receptors, cells can’t take in LDL, and blood-cholesterol skyrockets. Those with severe disease have inherited the defective gene from both parents, and have blood-cholesterols of about 500 to 1200 mg/100 ml (normal is less than 200 mg), and can die of heart disease before age 20.†

Those who inherit the defective gene from only one parent have about half the number of normal LDL receptors and a blood-cholesterol of about 300 mg/100 ml. They have severe atherosclerosis—especially men. In the past, one of six men with this genetic defect died of heart disease by age 40, and about two thirds of them died by age 60. The outlook now is better with earlier diagnosis and new drugs and treatments.

A cell’s LDL receptors and their role of pulling in cholesterol from blood were found by comparing cells from normal people with cells from people with familial hypercholesterolemia. For these discoveries, Michael Brown and Joseph Goldstein shared a Nobel Prize in 1985.

^{†The first person to get a simultaneous heart-liver transplant was Stormie Jones, who had familial hypercholesterolemia. Following a heart attack, she had the double transplant in 1984 at age 6 and died of a heart attack in 1990 at age 13.}

Smoking

Most people know that smoking causes lung cancer, but many don’t know that it markedly increases the risk of a heart attack or stroke. Carbon monoxide (from the smoke) displaces oxygen in the blood, so less oxygen gets to the tissues (Chap. 7). Nicotine constricts blood vessels, which means even less oxygen delivery and easier blockage of blood vessels by a clot.

Smoking also injures blood vessels, increases blood pressure, speeds up the heart beat, and increases the risk of blood clots. Among those who have heart attacks, sudden death is much more common in smokers. As expected, the risk goes up the more a person smokes.

The risk for cigar and pipe smokers lies between that for cigarette smokers and nonsmokers. By education level, college graduates smoke the least. (Figure 8.3).

Figure 8.3: % Smokers Age 25+ in 2018 by Education

About 90% of smokers begin smoking during childhood and adolescence. An effective way to cut smoking, especially in this age group, is to raise cigarette taxes. Canada’s smoking rate fell by a third when their cigarette tax was raised from 38¢ to $3.25/pack. But despite protests from antismoking groups, Canada then lowered the tax because of problems associated with smuggling in the lower priced/taxed cigarettes from the U.S. Cigarette tax in the U.S. is low compared to other developed countries.

Table 8-1: Risks of Smoking, Chewing, Vaping

High Blood Pressure

High blood pressure especially increases the risk of a stroke. High pressure can damage the lining of arteries and can be a determining factor in the formation and rupture of outpouchings in arteries. In the U.S., high blood pressure is much more common in Blacks than in Whites. Blacks of ages 15-84 have a much higher death rate from stroke than Whites of the same age and gender.

Male Gender

Men have a higher death rate from diseases resulting from atherosclerosis than do women of the same age and ethnicity (Figure 8.2). Men do smoke more, but sex hormones also make a difference. Male sex hormones lower HDL.* Premenopausal women have higher HDL than men of the same age. At menopause, women’s risk of heart disease goes up, but it takes years to catch up to men. Men have a head start.

^{*Anabolic steroids used illegally by some athletes are similar to the male hormone testosterone and lower HDL, raising the risk of atherosclerosis.}

High Blood-Homocysteine

The link between atherosclerosis and high levels of homocysteine in the blood was first seen in the genetic disease homocysteinuria.† Patients with this disease have extremely high levels of homocysteine and have severe atherosclerosis in childhood.

In the general population, the most common cause of high homocysteine is a folate deficiency. Since 1998, folate (a B-vitamin) has been added to refined staple grains like white flour. As a result, folate deficiency—and high homocysteine—is much less common.