Atherogenic risk factor

M. Yun, S. Jang, A. Cucchiara, A.B. Newberg, A. Alavi, F-FDG uptake in the large arteries A correlation study with the atherogenic risk factors, Semin. Nucl. Med. 32 (2002) 70-76. 

JB Ubbink. Vitamin nutrition status and homocysteine an atherogenic risk factor. Nutr Rev 52 383-387, 1994. 

Muthukumar, A., Zaman, K., Lawrence, R., Barnes, J.L., and Fernandes, G. (2003) Food Restriction and Fish Oil Suppress Atherogenic Risk Factors in Lupus Prone (NZB x NZW)F1 mice, J. Clin. Immunol. 23, 23-33. 

Microalbuminuria in healthy subjects is associated with atherosclerotic risk factors such as increased systolic and diastolic blood pressure (BP) decreased Apo A1 and HDL-C levels (12). Minor derangements of renal function are associated with an increase in CVD risk factors and promote progression of atherosclerosis (reviewed in ref. 14). However, in a separate study in contrast to BP, body mass index (BMl), and triglycerides (TGs), there was no relation between urinary albumin excretion and flow-mediated vasodilation in apparently healthy subjects. This suggests that the presence of atherogenic risk factors precedes the development of endothelial dysfunction in microalbuminuric but otherwise healthy subjects (75). 

Cardiovascular Major atherogenic risk factors among epileptic children, including altered metabolism of homocysteine. 

Kelly, F. D., Sinclair A. J., Mann N. J., Turner, A. H., Abedin, L. Li, D. (2001). A stearic acid-rich diet improves thrombogenic and atherogenic risk factor profiles in healthy males. Eur. J Clin. Nutr., 55, 88-96. 

Fatty acids play an important role as a risk factor for cardiovascular diseases, that is by forming plaques within the arteria. Low density lipoproteins (LDL) are seen as the most important risk factor. In the clinical chemistry laboratory, both LDLs and HDLs (high density lipids, considered as an anti-atherogenic factor) are determined. 

In addition to the five major risks, the ATP III guidelines recognize other factors that contribute to CHD risk. These are classified as life-habit risk factors and emerging risk factors. Life-habit risk factors, consisting of obesity, physical inactivity, and an atherogenic diet, require direct intervention. For example, emerging risk factors are lipoprotein(a), homocysteine, prothrombotic/proinflammatory factors, and C-reactive protein (CRP). C-reactive protein is a marker of low-level inflammation and appears to help in... 

The metabolism of VLDL by lipoprotein lipase in the capillaries in many tissues results in the formation of low density lipoprotein (LDL), which is atherogenic, so that diets high in sucrose are a risk factor for development of atherosclerosis. Many children in developed countries now consume large quantities of soft drinks containing sucrose or fructose. According to the above discussion, this could lead to atherosclerosis in later life. 

High-density lipoproteins (HDL) exert several ant/atherogenic effects. They participate in retrieval of cholesterol from the artery wall and inhibit the oxidation of atherogenic lipoproteins. Low levels of HDL (hypoalphalipoproteinemia) are an independent risk factor for atherosclerotic disease and thus are a target for intervention. 

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). 

It has been clear for several decades that an elevated concentration of plasma cholesterol attributable to increased concentrations of atherogenic lipoproteins (low-density lipoproteins [LDL] and remnant lipoproteins) is a major risk factor for the development of coronary heart disease (CHD) (Castelli et al., 1992 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 1993). The cholesterol biosynthetic pathway (Fig. 1) was a natural target in the search for drugs to reduce plasma cholesterol concentrations in the hope that these treatments would reduce the risk of CHD. However, early attempts to reduce cholesterol biosynthesis were disastrous. Tri-paranol, which inhibits the penultimate step in the pathway, was introduced into clinical use in the mid-1960s but was withdrawn from the... 

Even though milk fat contains some fatty acids that may elevate plasma total and LDL-cholesterol levels, which are risk factors for CHD, this effect is balanced by concurrent increases in levels of anti-atherogenic HDL-choles-terol. In addition, saturated fatty acids reduce plasma levels of atherogenic Lp[a] and produce a less atherogenic LDL particle size. Dietary intervention studies, where there was a substantial reduction in saturated fat intake and plasma cholesterol levels, did not produce an improvement in CHD or total mortality. Prospective epidemiological studies provide no evidence that saturated fatty acids are a risk factor for CHD. Indeed, in two large studies, saturated fatty acids were inversely associated with risk. 

Cholesterol Experiments from laboratory animal trials (21, 69, 70) have supported epidemiological studies (71) that link hypercholesterolemia and hyperlipoproteinameia, two risk factors for CVD, with dietary cholesterol intake or atherogenic fatty acid ratios. Common to many of these studies are the hndings that consumption of diets rich in cholesterol or saturated fat will result in a reduction of LDL receptors and elevation of LDL cholesterol and total cholesterol. 

As the knowledge of the pathogenesis of atherosclerosis rapidly increases, it appears that an active vascular endothelium, smooth muscle cells, and blood-borne cells such as monocytes and macrophages all play active roles in the atherosclerotic disease process. Risk factors, such as elevated plasma levels of certain lipids, prooxidants, and cytokines, may contribute to the chronic activation/stimulation as well as to the damage of the endothelium and other vascular tissues (160). There is evidence that supports the hypothesis that it is not only pure cholesterol and saturated fats but rather oxidation products of cholesterol and unsaturated fats (and possibly certain pure unsaturated fats) that are atherogenic, possibly by causing endothelial cell injury/dysfiinction. Lipid-mediated endothelial cell dysfunction may lead to adhesion of monocytes, increased permeability of the endothelium to macromolecules, i.e., a decrease in endothelial barrier function, and disturbances in growth control of the vessel wall. 

The response-to-injury hypothesis states that risk factors such as oxidized LDL, mechanical injury to the endothelium (e.g., percutaneous transluminal angioplasty), excessive homocysteine, immunologic attack, or infection-induced (e.g.. Chlamydia, herpes simplex virus 1) changes in endothelial and intimal function lead to endothelial dysfunction and a series of cellular interactions that culminate in atherosclerosis. C-reactive protein (CRP) is an acute-phase reactant and a marker for inflammation it may be useful in identifying patients at risk for developing CAD. The eventual outcomes of this atherogenic cascade are clinical events such as angina, MI, arrhythmias. 

TREATMENT OE LOW HDL-C The most frequent risk factor for premature CHD is low HDL-C. In patients with low HDL-C, the total cholesterol HDL-C ratio is a particularly useful predictor of CHD risk. A favorable ratio is. 5 and a ratio of >4.5 is associated with increased risk. Patients with low HDL-C may have what are considered to be normal total and LDL cholesterol levels however, because of their low HDL-C levels, such patients may be at high risk based on the total cholesterol HDL-C ratio (e.g., a total cholesterol, 180 mg/dL HDL-C, 30 mg/dL ratio, 6). A desirable total cholesterol level in low-HDL-C patients may be considerably lower than 200 mg/dL, especially since low-HDL-C patients may also have moderately elevated triglycerides, which may reflect increased levels of atherogenic remnant lipoproteins. Patients with average or high LDL-C, low HDL-C, and high total cholesterol HDL-C ratios have benefited from treatment. 

Importantly, recent population-based smdies indicate the existence of a continuous linear relationship between thyroid function and cardiovascular risk, regarding both the atherogenic and the metabolic profiles in fact, this relationship is valid over the entire range of thyroid function levels, encompassing both subcfinical hypothyroidism and euthyroidism, so that even low-normal TH or high-normal TSH levels may act as independent cardiovascular risk factors (Fazio et al, 2004). 

---