Low-density lipoprotein cholesterol lowering in the prevention of CHD: How low should we go?

Opinion statement The past 12 years have seen the publication of numerous randomized placebo-controlled studies using statins to lower low-density lipoprotein cholesterol (LDLC) to assess the efficacy of cholesterol lowering on cardiovascular events. Initial studies predominantly evaluated mortality or nonfatal myocardial infarctions and coronary heart disease (CHD) death in patients with known or presumed established coronary disease and moderately elevated to very elevated serum cholesterol concentrations. Subsequent investigations studied a broader spectrum of cardiovascular events as a composite primary end point in both primary and secondary prevention strategies in subjects with lower mean entry serum LDLC concentrations. These studies have generally shown a reduction in a composite end point of cardiovascular events, although not necessarily the more restricted end points used in previous studies. Although the LDLC mantra "lower is better" has been popularized in advertising and continuing medical education and suggested as an option in "very high risk" patients by the National Cholesterol Education Program Adult Treatment Panel, the precise target level for LDLC for optimal treatment has not been rigorously defined. Serum LDLC less than 100 mg/dL seems reasonable for patients with known atherosclerosis or at high risk for atherosclerosis (diabetes or presence of multiple risk factors). Serum LDLC less than 70 mg/dL may be a reasonable goal in the setting of acute coronary syndromes, but there are many problems with the data on which this recommendation is made. Furthermore, many advocates of "lower is better" seem oblivious to the potential downsides of more aggressive lipid-lowering therapy. The LDLC target in lower risk primary prevention is less clear. What is obvious is that moderate-dose statin therapy can lower CHD risk in primary prevention and secondary prevention with minimal side effects, and with the imminent availability of several generic statins, with great costeffectiveness.     

Lipid risk factor correlates of ischemic heart disease as diagnosed by myocardial perfusion scintigraphy

Patients with known coronary artery disease frequently change their lifestyles (e.g., diet, exercise, and smoking habit) after the diagnosis is made. Such changes can alter lipid risk factor levels and obscure etiologic risk factor associations with the presence of coronary artery disease. It is therefore preferable to determine the contribution of potential risk factors before the diagnosis of coronary artery disease has been established. In this trial, we used stress nuclear myocardial perfusion imaging to diagnose coronary artery disease in patients presenting for evaluation of chest pain. Two groups of age- and sex-matched patients were identified: a normal group (patients with no evidence of coronary artery disease), and an abnormal group (patients whose scans indicated the presence of significant coronary artery disease due to either fixed or reversible perfusion defects). Blood samples were drawn before scanning and analyzed for lipid risk factors. Compared to the normal group, the abnormal group had higher levels of triglycerides (189±91 vs. 135±51 mg/dL, p =0.003), lower levels of high density lipoprotein cholesterol (39±9 vs. 45±14 mg/dL, p =0.037), and higher levels of small, dense low density lipoprotein (LDL₃) (42±18 vs. 32±13 mg/dL, p =0.007). Total cholesterol, low density lipoprotein, and lipoprotein(a) levels were similar between groups. These findings suggest that ischemic heart disease, as assessed by myocardial perfusion scintigraphy, is more closely associated with the low high density lipoprotein/high triglyceride syndrome than with increased low density lipoprotein or total cholesterol levels.     

Lipoprotein(a) in coronary heart disease: a case-control study

To determine the significance of lipoprotein(a) levels in coronary heart disease patients, a case-control study was performed with 48 newly diagnosed coronary heart disease patients and 23 controls who were evaluated using clinical history and biochemical examination. Lipoprotein(a) was measured by quantitative latex-enhanced immunoturbidimetric method. Geometric means of biochemical parameters were obtained. Comprehensive lipid tetrad index was calculated using a previously validated formula. There was no significant difference in prevalence of diabetes, hypertension and smoking in cases and controls. Dietary intake of calories, fats, fatty acids and antioxidant vitamins was also similar. The levels of fasting glucose, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides were not significantly different in cases and controls (p > 0.05). Low-density lipoprotein/high-density lipoprotein ratio (4.33 +/- 1.5 vs 4.29 +/- 1.8) and total cholesterol/high-density lipoprotein ratio (6.59 + 1.7 vs 6.69 +/- 2.2) were similar. The mean lipoprotein(a) levels were significantly greater in cases (11.95 +/- 2.8 mg/dL, range 1-102 mg/dL) as compared to controls (6.68 +/- 3.4 mg/dL, range 1-73 mg/dL) (t = 2.08, p = 0.041). As compared to controls, in coronary heart disease cases, mean lipoprotein(a) levels in patients upto 50 years (10.27 +/- 2.8 vs 7.27 +/- 3.4 mg/dL) as well as those over 50 years (12.99 +/- 2.9 vs 4.91 +/- 3.5 mg/dL) were significantly more (p < 0.05). Coronary heart disease patients had a slightly greater prevalence of high lipoprotein(a) levels, 20 mg/dL or more (31.3 vs 13.0%; chi 2 = 2.83, l-tailed p < 0.05). Comprehensive lipid tetrad index (total cholesterol x triglycerides x lipoprotein(a) divided by high-density lipoprotein cholesterol) was also slightly higher in cases (14688.2 +/- 3.6) than in controls (8358.2 +/- 4.3) (t = 1.68, 1-tailed p < 0.05). This study shows that lipoprotein(a) levels are significantly more in both younger and older coronary heart disease patients as compared to controls.     

Treatment of lipid disorders in patients with diabetes

Optional statement The use of lipid-lowering drugs in diabetes is aimed primarily at reducing the large cardiovascular disease (CVD) risk burden experienced by this group of patients. Statin therapy has been shown to be highly efficacious in reducing CVD risk, both in those with and without prior CVD. Therefore, statins are the first-line lipid-lowering therapy in patients with diabetes. Patients with diabetes and established CVD should have low-density lipoprotein cholesterol (LDLC) lowered to at least 2.6 mmol/L (100 mg/dL) and, if possible, to 1.8 mmol/L (70 mg/dL). Those without prior CVD should have LDLC lowered to 2.6 mmol/L. Triglycerides should be kept less than 1.7 mmol/L (150 mg/dL) and high-density lipoprotein cholesterol (HDLC) above 1.15 mmol/L (40 mg/dL) in men and 1.2 mmol/L (46 mg/ dL) in women. Additional therapy with fibrates or nicotinic acid may be needed to achieve these goals; the choice is determined by tolerance and side-effect profile. The use of nicotinic acid or fibrates on their own to achieve triglyceride or HDLC levels should be limited to those patients already at or near LDLC goals. Caution is warranted with combination therapy because muscle side effects, in particular, can increase. In type 1 diabetes, CVD risk is high but trial data are sparse. Where there is nephropathy, and where glycemic control is poor, there will often be a need for triglyceride and HDLC raising interventions as above. In the absence of these, lipid profile is often normal and focus should be on reducing CVD risk by statin therapy. If uncertainty about CVD risk status exists, consideration should be given to using CVD imaging modalities to inform intervention choice in younger patients.     

Detection and evaluation of dyslipoproteinemia

Screening for dyslipoproteinemias should be undertaken in all individuals older than 20 years of age at least once every 5 years. The initial screening, as recommended by the Adult Treatment Guidelines Panel of the National Cholesterol Education Program, is to determine the concentration of total blood cholesterol. This initial determination can be made on blood obtained in the nonfasting state. Further evaluation of the patient's lipoprotein concentrations is dependent upon the presence of other cardiovascular risk factors. in the absence of definite coronary heart disease, hypertension, diabetes mellitus, a family history of coronary artery disease, cigarette smoking, or severe obesity, the patient with a total blood cholesterol concentration less than 200 mg/dL requires no specific instruction and should have a repeated screening performed within 5 years. Patients with blood cholesterol concentrations greater than 200 mg/dL should have their lipoprotein profiles determined if they have atherosclerotic cardiovascular disease or two other cardiovascular disease risk factors. The lipoprotein profile includes the determination of fasting cholesterol and triglyceride and HDL cholesterol concentrations. From these values, the LDL cholesterol concentration can be calculated. This LDL cholesterol concentration is central in selecting the appropriate therapy. HDL cholesterol concentrations may be useful in evaluating patients with ischemic heart disease. Concentrations of HDL cholesterol less than 35 mg/dL are associated with increased risk for coronary artery disease. Although there is currently no convincing evidence that support the specific treatment of depressed HDL cholesterol concentrations, therapy directed to modulating lipoprotein metabolism in patients with heart disease and low HDL concentrations may be of benefit. Patients with recurrent abdominal pain, pancreatitis, and eruptive xanthomatosis frequently have fasting hypertriglyceridemia concentrations exceeding 1000 mg/dL. These patients should be identified in order to effectively reduce their triglyceride concentrations, which can prevent these complications.     

Acute hepatitis C infection lowers serum lipid levels

Summary. Chronic hepatitis C infection is associated with hypolipidaemia that resolves with viral clearance. Lipid levels in a subgroup of patients rebound to levels that may increase the risk of coronary heart disease. The impact of acute hepatitis C infection and its clearance on lipid levels is unknown. We undertook a retrospective evaluation of subjects with acute hepatitis C infection evaluating lipid levels before, during and following acute infection. Thirty‐eight subjects with acute hepatitis C infection had lipid levels available. Twelve patients had pre‐infection and intra‐infection lipid levels available. Cholesterol (197.8–152.4 mg/dL, P = 0.025), low‐density lipoprotein (LDL) (116.1–76.3 mg/dL, P = 0.001) and non‐high‐density lipoprotein (non‐HDL) cholesterol (164.0–122.7 mg/dL, P = 0.007) decreased dramatically during acute hepatitis C virus infection. Nineteen patients who achieved viral clearance had lipid levels available during infection and following resolution of infection. In these patients, cholesterol (145.0–176.0 mg/dL, P = 0.01), LDL (87.0–110.1 P = 0.0046) and non‐HDL cholesterol (108.6–133.6 mg/dL, P = 0.008) increased significantly. No change was seen in patients who developed chronic infection. Four patients had lipid levels before, during and following resolution of infections and had increased postinfection LDL, cholesterol and non‐HDL cholesterol from pre‐infection levels, indicating acute infection may be associated with an increase in postinfection lipid levels and may confer an increased risk of coronary heart disease. Acute hepatitis C infection results in hypolipidaemia with decreased LDL, cholesterol and non‐HDL cholesterol levels that increase following infection resolution. Levels may increase above pre‐infection baseline lipid levels and should be monitored.     

Update on the role of triglycerides as a risk factor for coronary heart disease

Elevated triglyceride levels represent an independent risk factor for coronary heart disease, and recently the National Cholesterol Education Program revised the acceptable level of fasting triglycerides from less than 200 mg/dL to below 150 mg/dL. However, a sizeable proportion of people in Western societies has persistently elevated triglyceride levels. Fortunately, hygienic and pharmacologic measures can have a considerable impact on reducing triglyceride levels. However, an important yet unanswered question is whether decreasing triglycerides beyond low-density lipoprotein cholesterol lowering contributes significantly to additional coronary heart disease event reduction.     

Plasma lipoprotein (a) protein concentration and coronary artery disease in black patients compared with white patients.

PURPOSE: This study examines the relation between lipoprotein (a) protein levels and other lipid parameters and coronary artery disease in white and black patients. PATIENTS AND METHODS: Plasma lipoprotein (a) protein levels were measured prior to coronary angiography in a population of 127 white and 111 black patients. Each angiogram was given a total coronary artery disease score based on the number and severity of atherosclerotic coronary lesions. RESULTS: White and black patients exhibited no differences in total plasma cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Black patients had higher lipoprotein (a) protein levels than white patients (8.6 versus 4.0 mg/dL; p < 0.0001). The extent and severity of coronary artery disease was the same in white and black patients. White and black patients with coronary artery disease had higher lipoprotein (a) levels than patients without coronary lesions (4.37 versus 1.99 mg/dL, p = 0.027 for white; 9.23 versus 6.87 mg/dL, p = 0.072 for black). In both groups of patients, there was a weak but significant positive correlation between lipoprotein (a) protein levels and coronary artery disease score. CONCLUSION: Lipoprotein (a) is higher in patients with coronary artery disease. Black patients have higher plasma lipoprotein (a) protein levels than white patients and a comparable degree of coronary artery disease. It follows that the cardiovascular pathogenicity of lipoprotein (a) is not significantly greater in black patients despite higher lipoprotein (a) levels.     

High-density lipoprotein and coronary heart disease: lessons from recent intervention trials

Epidemiologic studies have consistently implicated low plasma high-density lipoprotein cholesterol as an important, independent risk factor for the development of coronary heart disease. However, clinical trials specifically designed to evaluate the role of lipid therapy in patients with low high-density lipoprotein cholesterol have only been recently reported. They include two trials with angiographic end points, the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial, and three clinical end points trials, the Air Force/Texas Coronary Atherosclerosis Prevention study, the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, and the Bezafibrate Infarction Prevention study. These and other trials clearly indicate that persons with coronary heart disease and high low-density lipoprotein cholesterol (>130 mg/dL [3.36 mmol/L]), with or without low high-density lipoprotein cholesterol, benefit from statin therapy. The Air Force/Texas Coronary Atherosclerosis Prevention study showed that persons at high risk of coronary heart disease but without known disease, who have moderate levels of low-density lipoprotein cholesterol as well as low levels of high-density lipoprotein cholesterol, also appear to benefit from statin therapy although the cost effectiveness of this approach is unclear. The results from the Department of Veterans Affairs High Density Lipoprotein Intervention Trial provide convincing evidence that patients without high low-density lipoprotein cholesterol and with established coronary heart disease and low high-density lipoprotein cholesterol benefit from gemfibrozil. This drug may be particularly beneficial for patients who, in addition to low high-density lipoprotein cholesterol, present with other features of the metabolic syndrome, such as obesity, glucose intolerance, and high triglycerides. Whether other fibrates, niacin, or statins lower coronary heart disease risk in persons with low high-density lipoprotein cholesterol in the absence of high or moderately high low-density lipoprotein cholesterol is unknown. (c)2000 by CHF, Inc.     

Current questions regarding the use of statins in patients with coronary heart disease

The discovery of statins caused a revolution in the field of lipid intervention. Statins are drugs with a good safety profile. Their clinical benefit has been extensively documented in primary and secondary prevention of coronary heart disease. There is substantial evidence that the clinical outcome can be improved with aggressive statin treatment both in patients with unstable as well as with stable coronary heart disease. Also, early administration of statins in acute coronary syndromes is accompanied by rapid clinical benefits, mainly through their "pleiotropic" action (anti-inflammatory, anti-thrombotic, improvement of endothelial function, etc) which is probably a lipid-independent effect. Moreover, emerging data indicate that statins can achieve additional benefit when low density lipoprotein (LDL) cholesterol reduction is coupled with C-reactive protein reduction (<2 mg/L). The prevailing message from the recent statin trials is that intensive LDL cholesterol lowering treatment with statins achieves further clinical benefit beyond that achieved with standard statin therapy. This should encourage the medical community to consider prescribing statins in every coronary patient, aiming at LDL cholesterol levels <100 mg/dL, preferably in the range of 70-80 mg/dL in stable coronary patients, while in coronary patients at very high risk, the optional target for LDL cholesterol levels should be in the range of 50-70 mg/dL.     

Use of statins for secondary prevention

Opinion statement The causal role of hyperlipidemia in the pathogenesis of atherosclerosis is beyond dispute. The principal lipid abnormality responsible for coronary heart disease (CHD) is considered to be the elevation of the low-density lipoprotein cholesterol (LDL-C), although reduced levels of high-density lipoprotein cholesterol, and most recently elevated triglyceride levels, have also been associated with increased risk for CHD. The risk with these lipid abnormalities exists both in the asymptomatic population as well as in individuals with clinical evidence of atherosclerosis. Most patients with established CHD, and noncoronary atherosclerosis, will need drug therapy to achieve their National Cholesterol Education Program Adult Treatment Panel LDL-C goal of less than 100 mg/dL; the most efficacious, safe, and well-tolerated drugs for this purpose are the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins. The role of statins for secondary cardiovascular disease prevention has been well established in several large randomized clinical trials. New data now suggest that statins offer significant benefits to a broad range of patients at high global CHD risk, and should be regarded as an integral part of the management of acute coronary syndromes.     

Effects of tamoxifen treatment on plasma lipids and lipoprotein lipid composition

Concern has been raised that long term treatment with the antiestrogen tamoxifen might predispose women to the rapid development of cardiovascular disease. Since estrogen-induced changes in plasma lipids confer protection to females from coronary heart disease, we have examined the impact of tamoxifen on lipoprotein levels and composition on eight posmenopausal women. After 3 months of tamoxifen treatment (10 mg, twice daily), no significant changes were observed in either whole plasma triglyceride (pre-Rx, 137 +/- 59; post-Rx, 157 +/- 110 mg/dL) or cholesterol (pre-Rx, 193 +/- 23; post-Rx, 204 +/- 14 mg/dL); plasma free (unesterified) cholesterol (FC), however, fell significantly (pre-Rx, 66.5 +/- 6.5; post-Rx, 59.6 +/- 4.6 mg/dL; P less than 0.05). Since plasma lecithin (L) was unchanged, the FC/L ratio declined significantly to levels observed in healthy menstruating women (pre-Rx, 95 +/- 0.16; post-Rx, 0.74 +/- 0.12 molar ratio; P less than 0.025). In low density lipoprotein (LDL), the concentrations of cholesterol and FC and the FC/L ratio all fell significantly (P less than 0.025, P less than 0.05, and P less than 0.025, respectively). Despite a tendency for high density lipoprotein2 cholesterol (HDL2-C) to increase (pre-Rx, 9.7 +/- 3.6; post-Rx, and 14.4 +/- 13.3 mg/dL; P less than 0.4) and phosphoinositol to fall, there were few clear-cut alterations in either HDL2 or HDL3 surface or core lipid composition. The combination of reduced HDL3 lysolecithin (P less than 0.025) associated with a posttreatment trend toward increased triglyceride/cholesterol esters ratios in both HDL subfractions are findings consistent with tamoxifen-induced inhibition of hepatic lipase. These changes in lipoprotein composition together with the fall in LDL cholesterol and increase in sex hormone-binding globulin (P less than 0.005) indicate that tamoxifen acts as an estrogen agonist on the liver. Since elevated LDL cholesterol levels and qualitatively altered lipoproteins enriched in FC are both associated with increased coronary risk, the improvement noted in these parameters after tamoxifen should allay to some degree anxiety about its use with regard to cardiovascular risk.     

Approach to Lipid Therapy in the Patient With Atherosclerotic Vascular Disease

Hyperlipidemia increases the incidence of atherosclerotic vascular disease and is associated with greater rates of recurrent cardiovascular events among individuals with established vascular disease. Several large population studies have confirmed the link between all cholesterol components (including elevated low-density lipoprotein [LDL] cholesterol, total cholesterol, and triglyceride levels, and reduced high-density lipoprotein [HDL] levels) with coronary heart disease and other manifestations of systemic atherosclerosis. In addition, landmark clinical trials have clearly established that lowering LDL cholesterol levels with statins (HMG-CoA reductase inhibitors) can lower recurrent cardiovascular events by nearly 25%. The benefits of altering non-LDL cholesterol levels (eg, triglycerides and HDL) are less clear, but several other medications are often used in conjunction with statins for cholesterol lowering. First-line therapy for lipid lowering in patients with atherosclerotic vascular disease includes statins and a recommendation for lifestyle changes (including diet and exercise). Second-line options for lowering cholesterol include fibrates, nicotinic acid, bile acid sequestrants, and ezetimibe. Therapeutic goals for patients with vascular disease are to achieve an LDL cholesterol level < 100 mg/dL, or <70 mg/dL in individuals at particularly high risk.     

Lack of change of lipoprotein (a) concentration with improved glycemic control in subjects with type II diabetes.

Recently, lipoprotein (a) [Lp(a)] has been identified as a major risk factor for coronary heart disease. No data are available on the effect of improved metabolic control on plasma Lp(a) concentrations in subjects with type II diabetes mellitus, a group at high risk for coronary heart disease. We examined the effects of improved metabolic control on plasma lipid and lipoproteins and Lp(a) concentrations in 12 subjects before and after 21 days of tight metabolic control. Glycosylated hemoglobin declined from 8.9% to 6.9% (P less than .002). Lp(a) increased slightly from 21.4 to 25.8 mg/dL (P = .119) with improved metabolic control. There were no significant differences in total, low-density, or high-density cholesterol values, although the decline in triglyceride concentrations was statistically significant. The distribution of apolipoprotein (a) [apo (a)] isoforms in subjects with type II diabetes mellitus was not unusual and the apo (a) isoform patterns did not change with improved metabolic control. Although the number of subjects was small, there was no decline in Lp(a) concentrations with improved control and thus the effect of glycemic control on Lp(a) concentrations may be much smaller in type II than in type I diabetes. These results suggest that diabetic subjects with elevated Lp(a) concentrations should have intensive management of conventional cardiovascular risk factors such as high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and blood pressure.     

Rhesus positivity and low high-density lipoprotein cholesterol: a new link?

The aim of the study was to investigate the relationship of ABO and Rh blood groups with lipid profile in patients with established multivessel coronary artery disease in a population with low levels of high-density lipoprotein cholesterol. The records of 978 patients with multivessel coronary artery disease, in whom coronary bypass surgery was performed, were investigated. Coronary risk factors including diabetes, hypertension, smoking, and obesity were noted for each patient. Serum lipid profiles: total cholesterol, low-density and high-density lipoprotein cholesterol, and triglyceride levels, were also recorded. The mean age of the patients was 59.3 +/- 9.7 years (range, 25-84 years) and 80% were male. The risk factors and lipid profiles of ABO blood types were similar. Rh-negative patients had higher levels of high-density lipoprotein cholesterol (46.9 +/- 9.9 vs. 41.6 +/- 10.4 mg.dL(-1), p = 0.001) and a lower total/high-density lipoprotein cholesterol ratio (4.8 +/- 1.3 vs. 5.2 +/- 1.6, p = 0.029) compared to Rh-positive patients. The other lipid levels and risk factors had no association with Rh typing. These results indicate a significant association between rhesus positivity and low levels of high-density lipoprotein cholesterol in patients with multivessel coronary artery disease.     

First-degree kinship with young coronary artery disease patients markedly increases lipid-level disorders in asymptomatic hypertensives

BACKGROUND: Association of hypertension and serum lipid disorders has been demonstrated in previous studies. However, there are no investigations about the behaviour of serum lipids in asymptomatic hypertensive individuals who are first degree relatives of young coronary patients. OBJECTIVE: To determine the degree of lipid disorders in Brazilian hypertensive individuals who are first degree relatives of young coronary patients. METHODS: There were four study groups, 2 in each arm of the study: a) 846 subjects without any evidence of heart disease or diabetes who were first degree relatives of patients who underwent coronary artery bypass grafting (CABG) surgery before 55 years-of-age. Of these subjects, 226 individuals were hypertensive (group Hyp F), and 620 were normotensive (group Normo F): b) 910 hospital employees without evidence of cardiovascular disease and family history of coronary artery disease of whom 152 were hypertensive (group Hyp NF), and 758 were normotensive (group Normo NF). Hypertension was defined as blood pressure greater than 140/90 mmHg. The following serum lipid measurements were performed: total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprtein cholesterol (LDLC), and triglycerides. Lipid disorders were defined according to the 2nd Report of the National Cholesterol Education Program (NCEP) (total cholesterol>240 mg/dl; LDLC>160 mg/dl; triglycerides>200 mg/dl). The frequency of lipid disorders in each group was calculated. Subjects were classified according to their body mass index (BMI) as normal, overweight, or obese. The following statistical analyses were performed as indicated: ANOVA (with Tukey's corrections for multiple comparisons), chi-square (x2), and odds ratio (OR). RESULTS: Hyp F subjects had significantly higher total cholesterol, LDLC and triglyceride levels, and significantly lower levels of HDLC than all other groups. There was a higher frequency of lipid disorders in Hyp F subjects than in Hyp NF individuals, with a significant OR of 1.71 (CI 1.26-2.32) and 2.09 (CI 1.48-2.72) for total cholesterol and LDLC respectively. When compared to Normo F subjects, Hyp F individuals had significantly higher risk of having lipid disorders: total cholesterol (OR=8), LDLC (OR=6), and triglycerides (OR=5). There was a higher frequency of obesity among Hyp F patients than in all other groups. The frequency of subjects who were overweight or obese was higher in Hyp F than in Hyp NF subjects. CONCLUSION: Hypertensive patients who were first degree relatives of patients revascularized at a young age had a higher prevalence of lipid disorders, particularly higher total cholesterol and LDLC, than hypertensive individuals without this family history. These individuals may have a greater genetic propensity to develop lipid disorders.     

Choice and use of blood lipid tests. An epidemiologic perspective

Serum cholesterol is a useful test in asymptomatic adults who are interested in preventing coronary heart disease (CHD). It guides the decision to recommend a fat-controlled diet to reduce the serum cholesterol level; this intervention probably decreases the risk of CHD in patients with high levels (eg, greater than 240 mg/dL), but not in those with lower levels (the majority). The potential effect of such intervention on absolute (attributable) CHD risk is relatively large in males and in patients with other risk factors. Dietary intervention probably has less effect on CHD risk than eliminating smoking or controlling hypertension. Lipid and lipoprotein tests other than cholesterol are not generally needed, although high-density lipoprotein cholesterol may be useful in certain situations. These epidemiologic considerations, tempered by the preferences of the patient, are useful for individualizing preventive medicine decisions.     

一项多中心、前瞻性、观察性研究评价氟伐他汀钠胶囊每日80 mg治疗的有效性及安全性

目的观察对于氟伐他汀钠胶囊40 mg日一次使用不能达标的稳定型心绞痛或2型糖尿病患者,剂量增加为40 mg每日两次的有效性和安全性。方法多中心、前瞻性、观察性上市后临床监测研究。该研究共纳入251例高脂血症合并稳定型心绞痛或2型糖尿病患者,这些患者经氟伐他汀钠胶囊40 mg睡前一次口服治疗至少4周后,低密度脂蛋白胆固醇(LDLC)未达标(>100 mg/dL)。经医生判断后根据临床需要将剂量增加至40 mg每日两次,共观察8周。主要疗效指标为治疗8周时LDLC水平与患者入组时即药物剂量增加前(基线)相比的变化;次要指标为第8周时LDLC的达标率、空腹甘油三酯(TG)、总胆固醇(TC)及高密度脂蛋白胆固醇(HDLC)水平与基线相比的变化以及安全性和耐受性。结果意向治疗人群(ITT)251例。氟伐他汀钠胶囊40 mg每日两次治疗终点时(第8周)ITT人群的LDLC较基线显著降低,总ITT人群、稳定型心绞痛和2型糖尿病患者LDLC较基线的降幅分别为27.3%、25.3%和28.9%(P均<0.001)。研究结束时59.4%的患者LDLC达标(<100 mg/dL),稳定型心绞痛和2型糖尿病患者的达标率分别为52.9%和67.2%。TG水平较基线显著下降,总人群、稳定型心绞痛和2型糖尿病患者分别下降17.02%、16.50%和17.78%(P均<0.001)。4例患者(1.6%)转氨酶(ALT/AST)升高>3倍正常值上限(ULN),其中3例氟伐他汀减量至40 mg每日一次后继续使用,没有患者出现肝脏症状或胆红素异常。研究过程中没有患者报告肌肉症状和/或肌酸激酶(CK)升高>5×ULN。结论对于应用氟伐他汀钠胶囊40 mg每日不达标的稳定型心绞痛或2型糖尿病患者,剂量增加至80 mg每日可以明显改善达标率,并且具有良好的安全性和耐受性。     

High risk for coronary heart disease in Thiruvananthapuram city: a study of serum lipids and other risk factors

There is a trend towards increase in the incidence of coronary heart disease among Indian population. Also, little information is available on the population distribution of serum lipid components and risk factors for coronary heart disease in Kerala, a state fast turning urban. To study the serum lipid profile and the prevalence of other risk factors for coronary heart disease in the residents of an urban housing settlement in Thiruvananthapuram, fasting blood sample was collected from 206 (64%) residents above the age of 19 years and analysed for plasma glucose and various fractions of serum lipids. A detailed questionnaire on the clinical profile and history of the subjects, and measured weights and heights was also administered. Mean serum total cholesterol was 223.7 +/- 45.3 mg/dL; 223.7 +/- 44.9 mg/dL among males and 223.7 +/- 45.8 mg/dL among females. Mean high-density lipoprotein cholesterol was consistently higher in females in all age groups, while mean low-density lipoprotein cholesterol was higher in males till the age group 40-49 after which the pattern was reversed. Mean total cholesterol in the age range 35-64, after age standardisation, was 229.4 mg/dL. Mean serum total cholesterol was higher in this sample when compared to US population, as well as north and west Indian populations. Thirty-two percent subjects were in the highest risk category with serum cholesterol exceeding 239 mg/dL, while in the US population this fraction constituted only 18 percent. Other risk factors such as high blood pressure, obesity, diabetes, sedentary lifestyle and smoking also had a high prevalence in this population. In this settlement of urban residents in Thiruvananthapuram, serum total cholesterol and low-density lipoprotein cholesterol are high. The causes are likely to be dietary. Combined with the high prevalence of other risk factors such as obesity, hypertension, smoking, diabetes and lack of exercise, this situation demands a preventive programme.     

Cholesterol, stroke risk, and stroke prevention

Serum cholesterol traditionally has been considered a poor predictor of total stroke risk; however, it is associated positively with ischemic stroke risk and associated negatively with hemorrhagic stroke risk. Although studies failed to demonstrate stroke reduction using older cholesterol-lowering medications, recent study of the statin class of medications shows both consistent stroke and other cardiovascular benefits. Ischemic stroke and coronary heart disease share similar underlying mechanisms, likely explaining much of the therapeutic benefit from statins. Current research is directed at further determining groups of patients most likely to benefit from lipid reduction in stroke prevention. In the interim, patients with established atherosclerosis should be treated with a statin to achieve a low-density lipoprotein cholesterol level less than 100 mg/dL.