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Atherosclerosis was relatively uncommon 100 years ago, when researchers first established its link to elevated cholesterol. As the twentieth century progressed, however, factors such as high-fat diets, sedentary lifestyles, cigarette smoking, and urbanization combined to increase the prevalence of both hypercholesterolemia and coronary heart disease (CHD) throughout the developed world. Atherogenesis begins at an early age and progresses throughout life, and cholesterol levels during young adulthood strongly predict the risk of CHD and related mortality during the ensuing decades. The total cholesterol level in youth also determines the actual age at which a critical level of atherosclerosis will be reached. Early studies on the primary and secondary prevention of CHD failed to identify a linear relationship between lipid lowering and risk reduction, primarily because older lipid-lowering agents lacked the potency to reduce cholesterol levels significantly enough to achieve lower cardiovascular event and mortality rates. The introduction of the statins, with their powerful lipid-lowering activity, overcame this limitation. Several large-scale trials of statins firmly established the efficacy of these agents in both primary and secondary CHD prevention. With the availability of statin therapy, we are now able to reduce the risk of major adverse CHD events by an average of 30%, regardless of patient age or gender.

The relationship between elevated serum cholesterol and cardiovascular disease, specifically coronary heart disease (CHD), has been and continues to be a source of debate in the medical community. Other issues under debate include criteria for screening for elevated cholesterol, criteria for treatment, and whether intervention to lower elevated cholesterol prior to a cardiac event is cost effective. Most physicians believe this latter statement to be true; however, reports of no decrease in overall mortality rates in those without clinical coronary disease in whom aggressive lowering of cholesterol is achieved may have contributed to the lack of consensus on this most important issue. In this presentation the evidence that links cholesterol and CHD is reviewed and it is demonstrated that lowering elevated cholesterol concentrations can improve quality of life and life expectancy.

OBJECTIVE: To determine whether the quantitative and qualitative effects on lipoproteins differ between two doses of conjugated equine estrogen before and after progestin administration. METHODS: We randomized 103 postmenopausal women into a control group and into two groups receiving either 0.625 mg or 1.25 mg of conjugated equine estrogen for 4 months and then the same estrogen dose plus cyclic medroxyprogesterone acetate for 8 months. RESULTS: Both estrogen doses similarly lowered (P < .01) low-density lipoprotein (LDL) cholesterol and raised (P < .01) high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I, triglyceride levels of all lipoproteins, and sex hormone-binding globulin capacity. Cyclic addition of the progestin reduced HDL cholesterol (P < .01) and apolipoprotein A-I (P < .05), but not LDL cholesterol in either estrogen group. A greater lowering of HDL cholesterol (P < .05) in response to the progestin was seen with the 0.625-mg dose of estrogen. Estrogen-induced triglyceride enrichment of HDL and LDL was not reversed by the progestin. CONCLUSION: The only significant quantitative difference in lipoprotein levels between the doses of conjugated equine estrogen before or after administration of medroxyprogesterone acetate was a greater decline in HDL cholesterol levels with the lower dose after 4 months of the progestin. This difference was not sustained over time. There were no differences between doses in the estrogen-induced triglyceride enrichment of lipoproteins, and these qualitative changes were not affected by the progestin.