12.3: Risk Factors

Risk estimates associated with traditional cardiovascular risk factors are overall similar in women and men across various regions of the World. However, the increased risk associated with hypertension and diabetes and the protective effect of exercise and alcohol appear to be larger in women than in men.[7] It is also important to make a difference between pre and post menopausal status.

Smoking

Smoking is the single most important preventable cause of IHD in women. It is a relatively large risk factor for myocardial infarction in women under the age of 55 when compared to men. Smoking enhances the inflammatory process, activates the coagulation system en promotes LDL oxidation. Smoking leads to down-regulation of the estrogen receptor in the endothelial wall leading to endothelial dysfunction and atherosclerosis. The combination of smoking and the use of oral contraceptives has a synergistic effect by inducing endothelial dysfunction and activation of the coagulation system. After cessation the risk declines rapidly.

Hypertension

Hypertension is a highly prevalent risk factor that becomes more common in women then in men and is particularly prevalent among black women.[7] After menopause the renine activity in plasma increases which leads to sodium retention. By the age of 60 almost 50% of all women have clinically manifest hypertension, defined as a systolic blood pressure > 140 mmHg and a diastolic blood pressure of 90 mmHg.[6] Hypertension in women compared to men more often leads to CVA, left ventricular hypertrophy en diastolic dysfunction. The structural changes of the myocardium can become clinical manifest by dyspnea, supraventricular tachycardia such as atrial fibrillation, angina due to endothelial dysfunction. Slightly elevated blood pressure leads in women more then in men to endothelial dysfunction.[6] Hypertension is 2 to 3 times more common in women taking oral contraceptives, especially among obese and older women. Blood pressure lowering strategies have demonstrated to reduce the risk of ischemic heart disease and stroke

Dyslipidemia

In women there is a stronger fluctuation of lipid levels throughout life. Due to hormonal changes total and LDL cholesterol levels increase with an average of 10-14% after menopause.[6] Low HDL and high triglycerides seems to be more important risk factors in women than in men. Data from the Nurses Health Study shows that HDL was the lipid parameter that best discriminated the risk of ischemic heart disease.[7] Hypertriglyceridemia is associated with a 37% increase in CVD risk in women compared to 14% in men.[7] The dynamic changes of the lipid profiles due to age and menopausal status play an important role in the prevention of cardiovascular disease in women.

Obesity

Obesity is an important risk factor for diabetes, hypertension and cardiovascular disease. There is a gradient of coronary risk with increasing overweight, with the heaviest category of women having a four-fold increased risk for CVD compared with lean women. Around menopause there is a shift from gynoid fat distribution to android. This central obesity in women leads more than in men to the metabolic syndrome, with an increased relative risk of insulin resistance, dyslipidemia and hypertension.

Diabetes

Diabetes is associated with a higher risk for ischemic heart disease in women than in men (RR2.0). This is partly due to a higher rate of coexisting risk factors in women with diabetes compared to men. Another important factor is that diabetes is more difficult to treat since less women reach treatment goals when compared to men. In women diabetes is an independent risk factor for developing heart failure. Diabetes during pregnancy has a 7-12 fold risk for developing diabetes later in life.

Women specific risk factors

Estrogens improve the arterial wall response to injury and inhibit the development of atherosclerosis by promoting re-endotheliazation, inhibiting smooth muscle cell proliferation and matrix deposition following vascular injury. They also have a vasodilative effect. Premenopausal women with hormonal dysfunction and estrogen deficiency have a higher risk for developing premature atherosclerosis.[6] The polycystic ovarian syndrome, a condition also known as PCOS have a high risk for developing the metabolic syndrome and type 2 diabetes and are therefore an at risk population. Also women with premature ovarian failure (menopause before the age of 40) have a higher risk for developing CVD.

“Novel” risk factors

In an effort to make a more accurate estimation of cardiovascular risk, more than 100 new risk markers have been proposed. There is however a slight resistance to use these markers since the lack of evidence that they really make risk estimation more accurate. A recent summary of systematic reviews conducted for the United States Preventive Services Task force has reviewed the evidence of 9 novel risk factors. Of the risk markers evaluated C-reactive protein was the best candidate for screening, however, evidence is still lacking to recommend routine use. The Reynolds Risk score, which is a risk score specifically designed for women, incorporated CRP which reclassified 15 % of the intermediate risk women to high risk.

Depression & Acute stress

Data from the INTERHEART study shows, that particular in women the combined exposure psychological risk factors such as depression, chronic emotional distress and acute stress such as major live events, are significantly associated with acute myocardial infarction (OR 2.6 in men and 3.5 in women). A stress-induced condition known as “Takotsubo cardiomyopathy” is almost exclusively seen among women. Due to severe emotional stress these women present with symptoms mimicking acute myocardial infarction. Also the ECG and echocardiogram show all the signs of infarction. However the CAG is often normal with no signs of coronary obstruction. The severe impaired left ventricular function usually normalizes completely after a couple of months.

Figure 12.3.1: Takso-tsubo cardiomyopathy