Introduction

Before the 1990s, coronary heart disease (CHD) was considered to be a disease that affected mostly men. However, it's been shown that, at the age of 40, while the risk of developing CHD in the course of a lifetime is 50% for men, it's 33% for women -- not an insignificant number. As more researchers became aware that CHD affects women as well as men, corresponding clinical studies began to be done more often in women. Accordingly, some of the inequality has been set right - women are now as likely to be investigated fully for CHD and appropriately treated as men. Gender differences in the relative importance of various risk factors will always exist, of course. A recent review by Netherlands researchers in Cardiovascular Research has looked at this.

Obvious Risk Factors

This group covers those risk factors that are easily evaluated by someone without a visit to the doctor or the lab for special tests:

Family history -- recent studies have shown that a family history of CHD in close relatives is a risk factor for women as well as for men. Indeed, some studies indicate the risk of premature CHD (i.e. before age 65) may be higher in women than in men.

Hormones -- the incidence of CHD is significantly lower in pre-menopausal women than in men of the same age, suggesting that the body's own estrogens have a protective effect on its development. This led to the use of hormone replacement therapy (HRT) with estrogen-progestin combinations, or estrogen replacement therapy (ERT) using estrogen alone, in the hope of protecting post-menopausal women from CHD. However, the latest results of the large Women's Health Initiative study show that HRT has the opposite effect on the risk of CHD (see first link below). The use of HRT to prevent or slow CHD in postmenopausal women cannot, therefore, be recommended; the jury is still out concerning possible benefits of ERT or selective estrogen receptor modulators (SERM), where long-term trials are still running.

Obesity -- this is a risk factor for CHD in both men and women, and 'apple' obesity is worse than 'pear' obesity. (This means that a big belly -- increased waist circumference and waist-hip ratio -- is more risky than excess fat on the thighs, etc.) Prevention of obesity is usually easier to achieve than reversing it and then keeping the weight off.

Smoking -- studies have suggested that smoking seems to be a stronger risk factor for heart attack (myocardial infarction, or MI) in middle-aged women than in men. There may be two reasons for this: smoking is associated with an earlier menopause (by 1-2 years), and smoking lowers high-density lipoprotein (HDL) cholesterol -- the 'good' cholesterol -- to a greater extent in women than in men. At all events, smoking is the most important preventable cause of CHD in both men and women. About 24% of women and 27% of men over 18 in the USA are current smokers.

What a doctor's visit can uncover

Apart from being told if you are obese, a trip to the doctor may uncover some other risk factors for CHD:

High blood pressure -- isolated systolic hypertension (ISH) is the type of high blood pressure most closely related to CHD and stroke.¹ It represents the age-related loss of elasticity in the arteries. The frequency of ISH increases more rapidly in women than in men after age 55. Large clinical trials show that antihypertensive drug treatment is equally successful in reducing the incidence of stroke and MI in both women and men with ISH.

Diabetes -- many people with diabetes are not diagnosed until some complication sends them to the doctor. Diabetes is a major risk factor for CHD, and, in fact, a greater factor in women than in men. Diabetic men have a two- to three-fold increased likelihood of CHD than non-diabetics, whereas diabetic women have a three- to seven-fold increased risk. And fatal MIs are significantly more common in diabetic women than in non-diabetic women and men with or without diabetes.

Psychosocial factors -- the family physician may be in a better position than the patient to recognize the increased risks of CHD associated with a lower educational level and low job control; these factors are probably equally relevant for women as for men.

Factors that need some blood work

Lipid profile -- total cholesterol and low-density lipoprotein (LDL) cholesterol levels are similar in men and women up to the menopause, but thereafter levels in women exceed those of men. Both are, of course, major risk factors for CHD. Although most large studies of cholesterol-lowering drugs have included men rather than women, recent studies with 'statin' drugs show that women respond just as well as men.

HDL levels are higher in women than in men in early adulthood, but decrease after menopause. It's been suggested that low HDL levels themselves are a major factor for CHD in postmenopausal women i.e. they don't need to be accompanied by raised LDL or triglyceride levels. In men, treatment of such 'isolated HDL elevation' reduces the risk of cardiovascular events; a similar study in women has not been reported, yet.

Triglyceride levels just after a meal also show a gender difference; pre-menopausal women have lower levels than postmenopausal women and men. In general, raised triglycerides increase CHD risk more in women than in men, presumably because this lipid promotes atherosclerosis.

Other lipid subclasses -- apolipoproteins A-1 and B, lipoprotein (a) - may be superior predictors of the risk of CHD than the standard lipid profile (i.e. total cholesterol, LDL, HDL, and triglyceride), but to date there is no good evidence of important gender differences.

Homocysteine -- elevated homocysteine levels are closely associated with the risk of CHD, to a similar degree in women and men. The exact role of homocysteine is, however, not fully understood.

Fibrinogen -- again, there's a significant association between fibrinogen levels and CHD in both women and men. Values are higher in women, and increase with age, obesity, smoking, post-menopause status, and the use of contraceptives. On the other hand, the closeness of the association lessens with age and after the menopause.

C-reactive protein (CRP) -- the role of inflammation as a cause of coronary arteriosclerosis has only recently emerged. CRP is a blood test indicating an inflammatory process in the body, and increased levels are linked to CHD in women and men of various ages. Two studies have shown that the relative risk is higher in women than in men. This test is likely to be used much more often in future.

Comment

The authors of this extensive review -- it covered 190 referenced publications -- reach the conclusion that, except for female hormonal status, no CHD risk factors are exclusively concerned with women or men. However, the presence of diabetes, HDL and triglyceride levels appear to have a measurably greater influence in women than in men, and there are hints that the same may be true for family history, smoking, and CRP levels (as an indication of inflammation).

While the gender differences in causation are not startling, it's possible there may be sex-related differences in responses to different forms of prevention and treatment of CHD. More studies should be done to see if that's really the case.