Dietary cholesterol and coronary heart disease

Dietary cholesterol has been known as a dominant factor in the genesis of atherosclerosis since 1908. The evidence for the role of dietary cholesterol is based upon animal experiments, the chemistry of atherosclerotic plaques, worldwide epidemiology, and human feeding studies. All lines of evidence converge to indicate that dietary cholesterol is a major factor in promoting the growth of the atherosclerotic plaque by increasing its cholesterol content. Confusion about dietary cholesterol has arisen because amounts above a certain quantity (the ceiling) do not elevate plasma cholesterol and low-density lipoprotein cholesterol. The therapeutic threshold for dietary cholesterol is below 100 mg/d.     

Fibrates and high-dose statins to prevent coronary heart disease events

Conclusions Atherosclerosis is a complex disease process with many factors influencing vascular biology. Lipoproteins are one of these factors that influences the growth and instability of arterial plaques. Clinical trials have established benefit from medical treatment directed at one lipoprotein fraction (LDL). Further basic research and clinical trials are needed to fully delineate the metabolic regulation and impact of other lipoproteins on atherogenesis.     

High-density lipoprotein cholesterol and coronary heart disease

There is a large body of evidence demonstrating an inverse correlation between circulating levels of high-density lipoprotein (HDL) cholesterol and cardiovascular disease risk. For every 1-mg/dL increase in HDL, it is estimated that the risk of cardiovascular events decreases by 2% to 3%. HDL is one of many factors that contribute to the regulation of the atherosclerotic process. HDL mediates reverse cholesterol transport and exhibits numerous beneficial properties, including antioxidant, antiinflammatory, and antithrombotic effects on the vasculature. Recent studies have expanded our understanding of the vasoprotective mechanisms of HDL to include enhanced nitric oxide production and improved endothelium-dependent relaxation. Progress has also been made in determining the molecular mechanisms that mediate reverse cholesterol transport. Recently published National Cholesterol Education Program Adult Treatment Panel guidelines have broadened the definition of low levels of HDL and encourage more aggressive screening and treatment of lipid abnormalities. Several therapeutic interventions can augment HDL concentrations, and there is increasing evidence that these interventions improve cardiovascular outcomes. Research focusing on defining the molecular roles of HDL will likely identify potential therapeutic targets for decreasing the incidence and progression of coronary heart disease. This review highlights the role of HDL in coronary heart disease, from basic mechanisms of action to recent clinical trial results.     

Global risk assessment for lipid therapy to prevent coronary heart disease

Randomized clinical trials have established that lipidlowering pharmacologic therapy can substantially reduce morbidity and mortality in patients with known coronary artery disease (CAD). Researchers are now working to define the role of lipid-lowering agents in the primary prevention of CAD to extend their benefit to patients at increased risk for future coronary events. The risk assessment models presently used for secondary prevention are not sufficient to identify high-risk, asymptomatic patients. Building on the accumulated data about the physiologic mechanisms and metabolic factors that contribute to CAD, novel serum markers and diagnostic tests are being critically studied to gauge their utility for the assessment of high-risk patients and occult vascular disease. New risk prediction models that combine traditional risk factors for CAD with the prudent use of new screening methods will allow clinicians to target proven risk reduction therapies at high-risk patients before they experience a cardiac event.     

Reducing oxidized lipids to prevent cardiovascular disease

Despite significant success in reducing plasma cholesterol, especially low-density lipoprotein cholesterol, risks for cardiovascular disease (CVD) complications remain. Among these risks are circulating levels of oxidative modified lipoproteins, primarily oxidized low-density lipoproteins (oxLDL). The evidence supporting oxLDL as a potential target for therapeutic management to reduce metabolic complications and CVD events is reviewed in this report.     

Can menopausal hormone therapy prevent coronary heart disease?

Observational studies show that women who take menopausal hormone therapy (MHT) have a greatly reduced risk of coronary heart disease (CHD). But in some large randomized controlled trials, MHT failed to decrease CHD and so has been deemed inappropriate for long-term prophylaxis against atherosclerosis or other chronic diseases associated with the menopause. Despite the apparent strength of this conclusion, several recent reports suggest that MHT could be atheroprotective when started close to the menopause, and effects of early discontinuation of MHT have never been studied in randomized trials. Here, we examine these reports and highlight existing uncertainty regarding the effects of long-term continuation versus early discontinuation of early-start MHT on atherosclerosis and CHD risk. We call for new research on this question, and an evidence-based review of existing recommendations for MHT.     

Antibiotic therapy for treatment of Chlamydia to prevent coronary heart disease events

Evidence is mounting that infectious agents might be involved in atherosclerosis. Therefore, antibiotic therapy might be helpful in its prevention. Early pilot therapeutic trials have targeted Chlamydia pneumoniae because it has the most evidence associating it with atherosclerosis. Small, randomized pilot trials that test the effect of macrolide therapy on future clinical events in patients with coronary artery disease have already shown promising but mixed results. Large clinical trials are presently underway that should provide more definitive information regarding the use of antibiotics in coronary artery disease. Until the results of these studies are available, it is not recommended that antibiotic therapy be routinely utilized for the treatment or prevention of complications of atherosclerosis.     

Does lowering serum cholesterol levels lower coronary heart disease risk?

Many lines of evidence converge toward the conclusion that low-density lipoprotein cholesterol (LDLC) is indeed a causal factor in the genesis of CHD. These range from animal studies, pathology studies, inborn errors of metabolism, clinical observations, and the existence of plausible biologic mechanisms, to the vast body of epidemiologic evidence. Observations of the association of LDLC with CHD hold between different populations, in the same population at different times, and to studies of individuals within populations. Finally, the clinical trials of cholesterol lowering, together with regression studies in animals and angiographic studies in humans, provide compelling evidence that the progress of atherosclerosis can be halted and the clinical sequelae can be reduced. The newly available results from more recent intervention studies have reinforced the validity of this conclusion. The intervention studies reduced the CHD incidence rate by approximately 2% for every 1% reduction in total cholesterol (TC) even though the studies were of relatively short duration (typically 5 years). More prolonged exposure to lower TC levels can be expected to yield even greater ultimate benefit. The benefit is most clearcut for men at highest risk. The combined data indicate that both fatal and nonfatal CHD can be reduced. More data on the extremes of age, on subjects with moderate elevations of TC, and on women would be valuable, but it is reasonable to proceed with advice to the general population aimed at reducing average cholesterol levels, and also to identify and treat those at high risk. There is good reason to expect that these measures will further reduce MI events and in all likelihood also MI deaths. Whether they will also reduce overall mortality is at present a moot point; however, a reduction in the burden of nonfatal MI would in itself be a very desirable objective.     

The Importance of lowering cholesterol in patients with coronary heart disease

Patients with prior manifestations of cardiovascular disease account for about 50% of all myocardial infarctions and 70% of deaths due to coronary disease. The benefits of lowering elevated cholesterol levels in patients with coronary disease are well documented. Recent clinical trials indicate that these benefits, in terms of reduced risk of cardiovascular morbidity and mortality, extend even to patients with “average” cholesterol levels and support the importance of reaching a target low-density lipoprotein cholesterol level of ≤ 100 mg/dl. These findings argue in favor of attaining and maintaining optimal lipid targets for secondary (and primary) prevention of atherosclerotic vascular disease in patients at risk.     

Failure of captopril to prevent nitrate tolerance in congestive heart failure secondary to coronary artery disease

The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.     

Diet, cholesterol and coronary heart disease. A perspective.

After pioneering, scattered observations in the context of the so-called geographical pathology, collected during the first part of this century, a systematic approach into the search of causality of the association between diet and coronary heart disease has characterized the past 50 years. The possible link of eating habits leading to a diet high in calories, total fat, saturated fatty acids and cholesterol, to coronary events, through the mediation of serum cholesterol, represents the classic diet-heart theory. This theory is supported by results from ecological analyses, prospective studies, animal experiments, clinical observations, controlled trials, biochemical and nutritional studies. This traditional view of the problem has partly changed recently and a number of other dietary components in the possibly causal chain have emerged, with effects not necessarily involving serum cholesterol and lipids. The role of other nutrients in the atherosclerotic process and of precipitating factors (e.g. vitamins, anti-oxidants, fibre, sub-categories of fatty acids, phytosterols, flavonoids, etc.) has been identified but is not always fully understood. At the same time other blood lipids, other blood components and other pathways have been identified between diet and coronary outcomes. New challenges are open for future research since the association of diet with coronary disease is not as simple and linear as supposed. The main issues are the need to explain a number of still unknown mechanisms, to determine which "natural diet" carries the minimum coronary risk and whether "new" foods produced by modern technology are really needed to contrast this epidemic.