Cholesterol optimal levels

The National Cholesterol Education Program Adult Treatment Panel III guidelines have set the optimal level for low-density lipoprotein (LDL) cholesterol for all adults as less than 100 mg/dL (2.59 mmol/L). 

Most men and women have had their blood pressure measured at one time or another. But, bearing in mind that without knowing it, many individuals have either pressure above optimal levels or frank hypertension, if you haven t had a test lately, call your doctor s office and schedule an appointment. While you re there, it would be a good idea to have your cholesterol levels checked as well. Elevated cholesterol counts are not only a major risk factor for heart attack and stroke, in and of themselves, but they also predispose a person to developing hypertension. 

The possibility that vitamins might have physiological functions beyond the prevention of deficiency diseases was first recognized in 1955 with the finding (8) that niacin can affect semm cholesterol levels in humans. An explosion of research (9—11) in the intervening years has been aimed at estabUshing optimal vitamin levels and anticipating the health consequences. 

The development of CHD is a lifelong process. Except in rare cases of severely elevated serum cholesterol levels, years of poor dietary habits, sedentary lifestyle, and life-habit risk factors (e.g., smoking and obesity) contribute to the development of atherosclerosis.3 Unfortunately, many individuals at risk for CHD do not receive lipid-lowering therapy or are not optimally treated. This chapter will help identify individuals at risk, assess treatment goals based on the level of CHD risk, and implement optimal treatment strategies and monitoring plans. 

Table 22.2 Optimal and desirable levels of serum total cholesterol and LDL-cholesterol levels...

Lipoprotein disorders are detected by measuring lipids in serum after a 10-hour fast. Risk of heart disease increases with concentrations of the atherogenic lipoproteins, is inversely related to levels of HDL, and is modified by other risk factors (Table 35-1). Evidence from clinical trials suggests that LDL cholesterol levels of 60 mg/dL may be optimal for patients with coronary disease. Ideally, triglycerides should be below 120 mg/dL. Differentiation of the disorders requires identification of the lipoproteins involved (Table 35-2). Diagnosis of a primary disorder usually requires further clinical and genetic data as well as ruling out secondary hyperlipidemias (Table 35-3). 

In the SC lipids form two crystalline lamellar phases.27 The mixture of both phases produces the optimal barrier to water loss from SC. The balance between the liquid crystalline and the solid crystal phases is determined by the degree of fatty acid unsaturation, the amount of water, and probably by other yet undiscovered factors. A pure liquid crystal system, produced by an all-unsaturated fatty acid mixture, allows a rapid water loss through the bilayers with a moderate barrier action. The solid system produced with an all-saturated fatty acid mixture causes an extreme water loss due to breaks in the solid crystal phase.6,23 Studies with mixtures prepared with isolated ceramides revealed that cholesterol and ceramides are very important for the formation of the lamellar phases, and the presence of ceramide 1 is crucial for the formation of the long-periodicity phase.27 The occurrence of dry skin associated with cold, dry weather for example, may result from an extensive, elevated level of skin lipids in the solid state. Therefore, a material that maintains a higher proportion of lipid in the liquid crystalline state may be an effective moisturizer.6... 

The latter term really represents VLDL cholesterol. It is now recognized that serum apoprotein determinations provide the best cardiovascular disease risk evaluation high levels of ApoB-100, especially ApoLp(a), are associated with a high disease risk, but high levels of ApoA-I are associated with a low risk. The optimal LDL/HDL cholesterol ratio is 3 or less. 

In a study at the University of North Carolina involving about nine thousand men and women over a period of 11.6 years, the rate of cardiovascular disease increased significantly as blood pressure levels increased. Compared with patients who had optimal blood pressure levels, those with high-normal measurements had two and a half times the risk of developing cardiovascular disease. That statistic took into consideration other factors involved in the disease. Most of the risk was in the form of a stroke. The risk was greatest for African Americans, diabetics, overweight and obese individuals, and people with high levels of LDL cholesterol. 

Other conditions previously mentioned in this chapter, such as cancer, immunocompetence and interferon production, antihistamine eflFects in colds, increased iron absorption, eflFects on cholesterol metabolism, and nitrosamine blocking, were studied at higher than RDA dosage levels. These many situations require additional research study to determine what the minimum levels are to attain the optimal health condition. 

Ezetimibe is used for secondary prevention against established atherosclerotic CVD to achieve an optimal atherogenic cholesterol level in patients with intolerance to high-doses of statins. It can further be used in combination with statins to achieve lower LDL-C levels in very-high-risk patients [59]. Ezetimibe inhibits the Niemann-Pick Cl-Like 1 (NPClLl)-dependent intestinal cholesterol absorption in the apical brush border membrane of jejuna enterocytes [14], and thus it only moderately lowers LDL-C (12-25 %) [60]. Meanwhile, common adverse effects associated with ezetimibe therapy include gastrointestinal disturbances, while infrequent adverse effects such as rash, angioedema, anaphylaxis, hepatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis may occur [46]. 

The mechanism by which n-3 fatly acids are able to reduce the cholesterol level is still unclear, although some hypotheses have been advanced. For example, Bourre (1991) claimed that a-linolenic acid controls the composition of nerve membranes. Salem (1995) proposed that docosahexaenoic acid [DHA or (22 6n-3)] controls the composition and functions of the neuronal membrane. We recently reviewed a number of studies that provided support for apreferred n-3/n-6 ratio of 1 4 (Yehuda, et al., 1993). Itis possible that such a ratio optimizes uptake into the brain and its eventual incorporation into the neuronal membranes. 

For now, in patients with established CHD it is recommended to initiate diet and lifestyle changes along with statin therapy to target an LDL of 70 mg/dL or less and then, if the HDL is <40 mg/dL, to consider adding a fibrate or niacin to raise the HDL cholesterol level. Of note, no specific level of HDL was set in the recent ATP III guidelines, further adding to the uncertainty of how to optimally treat low HDL cholesterol levels. 

Obviously, individuals with higher cholesterol and LDL levels are more susceptible to these detrimental effects than those with normal cholesterol and LDL levels. Total plasma cholesterol levels less than 200 mg/dL are considered desirable. Levels above 240 mg/dL are considered high, and levels between 200 and 239 mg/dL are considered borderline. For LDL, plasma levels of less than 100 mg/dL are considered optimal, plasma levels equal to or greater than 160 are considered high, plasma levels between 130 and 159 mg/dL are considered borderline, and plasma levels between 100 and 129 are considered above optimal. Current guidelines (8,13) also recommend an LDL level below 70 mg/dL as a goal for very high-risk patients (i.e., those with multiple risk factors and known cardiovascular disease). 

Cholesterol extraction studies listed in Tables I and II have progressed from the initial scale to an optimization phase at the laboratories of the University of Wisconsin and Phasex Corporation (35. Whereas all the applications listed in Table II are interesting for discussion, fish oils extraction and enzyme reactions were selected for their newness and/or novelty for discussion here. Fish oil extraction with supercritical fluids exhibits the potential to become the preferred separations process if high concentration levels of eicosapentanoic acid are required, and it is being in vestigated by many workers. The subject of enzyme reactions in supercritical fluids is, at present for the most part, an interesting academic pursuit but it exemplifies the breadth of application of supercritical fluid extraction. 

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