Cholesterol and CHD

Clinical studies show that dietary cholesterol is a less potent regulator of plasma cholesterol than are saturated fatty acids. Results from meta-analyses predict that plasma cholesterol response to a 100 mg/day change in dietary cholesterol will be from 0.06 to 0.07 mmol/L. The data show that although dietary cholesterol elevates plasma total cholesterol and LDL-cholesterol level, it also increases the level of HDL-cholesterol such that there is little overall effect on the LDL HDL ratio (McNamara, 2000). 

Numerous international comparative studies found significant positive correlations between per capitut consumption of cholesterol and CHD mortality using simple univariate regression analysis (McNamara, 2000). 

Ravnskov (1995) listed cholesterol intake for CHD patients and controls from 14 within-country longitudinal studies. In only two of these studies were CHD patients found to have a statistically significantly higher intake of cholesterol than control subjects. 

Kritchevsky and Kritchevsky (2000) provided a summary of the evidence linking dietary cholesterol to the risk of CHD in 10 cohorts from eight large, well-conducted prospective studies that were reported since 1980, which included the Nurses Health Study, the Health Professionals Followup Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. In eight of the cohorts there was no statistical association between cholesterol intake and the risk of CHD. In one of the positive studies the association was established by simple univariate analysis and was not adjusted for other dietary variables. The other study adjusted only for fat intake. There is no compelling evidence from these epidemiological studies that dietary cholesterol is associated with the risk of CHD. 

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More recently the term hyperlipoproteinemia has become useful. Saturated fatty acids, usually esterified to glycerol as triacylglycerides (i.e., fats), can be related to cardiovascular disease since they increase plasma cholesterol levels. This cholesterol is now known to be primarily associated with a low-density lipoprotein (LDL) fraction. Lipoproteins are complex particles consisting of proteins, triacylglycerol (fat), phospholipids, cholesterol, and cholesterol esters. LDL has density of 1.00-1.06 and contains at least 45% cholesterol. It is the cholesterol found in the LDL fraction that is the harbinger of human arterial plaque manifested as atheroma. An inverse relationship has been established between cholesterol in high-density lipoprotein (HDL) (d = 1.20, 18% cholesterol) and CHD. HDL transports cholesterol from accumulation in arterial walls to the liver for biodegradation. 

PUFAs are categorized as n-6 PUFAs (mainly derived from linoleic acid) and n-3 PUFAs (mainly present in fatty fish and also derived from alpha-linoleic acid). Clinical trials, in which n-6 PUFAs (containing linoleic acid) were substituted for SFAs showed a greater impact on reduction of both plasma cholesterol and CHD risk, in contrast to trials where low-fat diets were employed. 

Patients with metabolic syndrome are twice as likely to develop type 2 diabetes and four times more likely to develop CHD.3,11 These individuals are usually insulin resistant, obese, have hypertension, are in a prothrombotic state, and have atherogenic dyslipidemia characterized by low HDL cholesterol and elevated triglycerides, and an increased proportion of their LDL particles are small and dense.3... 

LC is a 51 -year-old female with a history of CHD (stent placement in the left anterior descending coronary artery 3 years prior) and type 2 diabetes who is referred to you for follow-up of her cholesterol. She is taking simvastatin 20 mg once daily in the evening for her cholesterol, and metformin 2000 mg once daily in the evening and piogliti-zone 15 mg once daily for diabetes. Her diabetes is well controlled. Her laboratory test results are within normal limits, except for her fasting lipid profile total cholesterol 215 mg/dL (5.57 mmol/L), triglycerides 135 mg/dL (1.53 mmol/L), HDL cholesterol 51 mg/dL (1.32 mmol/L), and LDL cholesterol 137 mg/dL (3.55 mmol/L). 

Cholesterol, triglycerides, and phospholipids are transported in the bloodstream as complexes of lipid and proteins known as lipoproteins. Elevated total and LDL cholesterol and reduced HDL cholesterol are associated with the development of coronary heart disease (CHD). 

In patients with known CHD the 4S (16), Cholesterol and Recurrent Events (CARE) (17) and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID)... 

Robust epidemiologic evidence has identified an inverse relationship between HDL-cholesterol levels and CHD risk. Indeed, HDL-cholesterol is included in the Framingham CHD risk prediction scores (29). HDL-cholesterol protects against... 

The purpose of altering plasma lipoprotein levels is to reduce the risk of coronary events. The results of outcome trials are available for lovastatin (Downs et al, 1998), simvastatin (Scandinavian Simvastatin Survival Study Group 1994), and pravastatin (Shepherd et al, 1995 Sacks et al, 1996 The Long-Term Intervention With Pravastatin in Ischaemic Disease (LIPID) Study Group, 1998). Three of these trials, 4S, Cholesterol and Recurrent Events (CARE), and LIPID, studied patients with CHD, whereas the West of Scotland Coronary Revention Study Group and the Air Force Coronary Atherosclesosis Prevention Study (AFCAPS) evaluated the benefits of therapy in patients without known CHD. The main results of these trials are summarized in Tables la and lb. 

A number of studies, including several large prospective studies, such as the Framingham Study (Anderson et al, 1987), the Multiple Risk Intervention Trial (Stamler et al, 1986) and the Lipid Research Clinics Program (Pekkanen et al., 1990), as well as the Seven Countries Study (Verschuren et al, 1995) showed a positive correlation between levels of plasma cholesterol and mortality from CHD. However, epidemiological associations cannot prove causality and elevated cholesterol levels could be either a cause, a correlate or a consequence of CHD. 

Braunwald (1997) points out that fully half of all patients with CHD do not have any of the conventional risk factors (hypertension, hypercholesterolemia, cigarette smoking, diabetes mellitus, marked obesity and physical inactivity). Further, up to two-thirds of patients with CHD have what may be considered normal serum cholesterol levels (see references in Parodi, 2004). These facts suggest that the role of plasma cholesterol in CHD has been overemphasized and oversimplified. 

A consequence of the lipid hypothesis of CHD is that reduction of saturated fat and cholesterol and an increase of polyunsaturated fatty acids in the diet will lower plasma cholesterol level with a reduction in the risk of CHD. A causal relation between dietary fat and CHD can be established only by conducting randomized clinical trials. 

Statin Drugs and CHD. Statin drugs are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that act by inhibiting HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis. The statins are now the most commonly prescribed drugs for the treatment of hypercholesterolemia. They can reduce plasma total cholesterol by 20-42%, LDL-cholesterol by 25-55% and triglycerides by 10-35%. In addition,... 

Evidence from well-conducted prospective epidemiological studies does not suggest that consumption of saturated fat and cholesterol is associated with an increased risk of CHD. Randomized clinical trials that reduced the intake of saturated fatty acids and cholesterol and increased the intake of polyunsaturated fatty acids to lower plasma cholesterol levels did not significantly improve CHD or total mortality. The minor improvement in CHD events for trials of the potent cholesterol-lowering statin drugs may result, to an unknown extent, from their pleiotropic effects and cannot be used to justify the lipid hypothesis. 

Early investigations into a link between dietary tram fatty acid (TFA) intake and plasma cholesterol level in clinical trials, and CHD in epidemiology studies provided conflicting results. This outcome resulted from small numbers of participants in the trials combined with poor experimental... 

These proteins are of great interest because of their relationship to coronary heart disease (CHD). Lipoproteins, a group of macromicellar complexes of lipids and proteins, are closely associated with the risk of developing CHD. Structurally, lipoprotein particles contain a nonpolar lipid core of triglycerides and cholesterol esters and a polar surface that is comprised of apolipoproteins and unesterified cholesterol and phospholipids. There are three principle classes of lipoproteins ... 

The absolute CHD risk is computed using risk equations based on the Framingham cohort in reality this means consulting a simple colour-coded chart armed with data about the patient including age, sex, smoking status, pretreatment blood pressure and plasma total and LDL cholesterol, and presence or absence of diabetes. ... 

Coronary heart disease (CHD) is one of the leading causes of morbidity and mortality in the United States. Hyperlipidemia is a major risk factor for atherosclerosis and CHD. Hyperlipidemia is defined as an elevation in blood cholesterol or triglycerides (TG). Lipids are primarily transported in the body by three major lipoproteins low-density (LDL), very-low-density (VLDL), and high-density lipoproteins (HDL). Cholesteryl esters and TG are carried by the lipoproteins, which vary in size and composition of cholesterol and... 

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