Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP)

BACKGROUND: The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of < 4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of < 4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate. CONCLUSIONS: The results of this study support the concept that serum lipids are CHD risk factors in older Americans.     

Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. METHODS AND RESULTS: The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients.     

Influenza virus inhibits cleavage of the HSP70 pre-mRNAs at the polyadenylation site

BACKGROUND: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory. OBJECTIVE: To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease. DESIGN: In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L. RESULTS: Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change. CONCLUSION: The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations.     

Prevalence and identification of abnormal lipoprotein levels in a biracial population aged 23 to 35 years (the CARDIA Study). The Coronary Artery Risk Development in Young Adults Study

This study examines the prevalence of abnormal low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels in young adults to determine the ability of National Cholesterol Education Program Adult Treatment Panel (ATP) guidelines to identify persons with elevated LDL cholesterol, to compare other algorithms with those of the ATP, and to determine the contributions of race, gender, and other coronary artery disease risk factors to identifying patients with elevated LDL and low HDL cholesterol. The cohort was population-based, aged 23 to 35 years, and included relatively equal numbers of blacks and whites, and men and women. The prevalence of LDL cholesterol > or = 160 mg/dl (> 4.1 mmol/L) was 5% in black women, 4% in white women, 10% in black men, and 9% in white men. ATP identified most participants with elevated LDL cholesterol (range: 58.8% of white men to 70.7% of black women). Lipoprotein panels would have been required in 6% to 7% of women and to 15% to 18% of men. Algorithms that used nonlipid risk factors required more lipoprotein panels and identified fewer additional participants at risk. The prevalence of HDL cholesterol < 35 mg/dl (0.9 mmol/L) was 3% in women, 7% in black men, and 13% in white men. Algorithms that used nonlipid risk factors before measuring HDL cholesterol would require HDL cholesterol measurements in 35% of whites and 56% of blacks, but reduced sensitivity for identifying low HDL cholesterol (range: 58% in white men to 93% in black women). In young adults, algorithms based on nonlipid risk factors and family history have lower sensitivity, and increase rather than decrease the number of fasting lipoprotein panels required when compared with ATP levels.     

Inadequate control of lipid levels in patients with a previous myocardial infarction

AIM: To access the current lipid management of late survivors of acute myocardial infarction. METHODS: A systematic follow-up of all survivors who had previously been screened for enrolment into one of three randomised clinical trials in Auckland was undertaken from December 1995 to January 1997. All contacted survivors were asked to answer a questionnaire regarding their current therapy and were invited to undergo venepuncture for a lipid assay. RESULTS: Of the 1036 patients with acute myocardial infarction screened for enrolment in the three trials there were 984 (95%) who survived 30 days. At a median of 5.5 years (interquartile range 3.2-8.5) follow-up, 641 (86%) survivors agreed to have a fasting lipid test. The mean total cholesterol level was 5.7 +/- 1.1 mmol/L high density lipoprotein cholesterol 1.1 +/- 0.3 mmol/L, low density lipoprotein cholesterol 3.8 +/- 0.9 mmol/L and triglyceride level 1.9 +/- 1.1 mmol/L. Two hundred and seven (32%) patients were treated with a lipid-modifying agent. Four hundred and forty-five (69%) patients had a cholesterol level > or = 5.2 mmol/L 381 (59%) patients had a level > or = 5.5 mmol/L and 72 (11%) patients had a level > or = 7.0 mmol/L of whom 62 patients were not being treated with a lipid-modifying agent. For the 107 patients with coronary artery bypass grafts, the mean cholesterol level was 5.4 mmol/L and the mean low density lipoprotein cholesterol level was 3.7 +/- 0.9 mmol/L, with 57 (53%) patients not being treated with a "statin" or "fibrate". CONCLUSION: Lipid management is suboptimal in this high risk population of patients post-infarction and greater efforts need to be made to achieve better control. Diet is frequently inadequate in these patients at high risk and statin therapy is indicated.     

The role of reproductive factors and use of oral contraceptives in the aetiology of breast cancer in women aged 50 to 74 years

BACKGROUND: We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind, placebo-controlled, prospectively randomized 12-wk controlled trial at a university research center. OBJECTIVE: We evaluated the lipid-lowering effects of this red-yeast-rice dietary supplement in US adults separate from effects of diet alone. DESIGN: Eighty-three healthy subjects (46 men and 37 women aged 34-78 y) with hyperlipidemia [total cholesterol, 5.28-8.74 mmol/L (204-338 mg/dL); LDL cholesterol, 3.31-7.16 mmol/L (128-277 mg/dL); triacylglycerol, 0.62-2.78 mmol/L (55-246 mg/dL); and HDL cholesterol 0.78-2.46 mmol/L (30-95 mg/dL)] who were not being treated with lipid-lowering drugs participated. Subjects were treated with red yeast rice (2.4 g/d) or placebo and instructed to consume a diet providing 30% of energy from fat, <10% from saturated fat, and <300 mg cholesterol daily. Main outcome measures were total cholesterol, total triacylglycerol, and HDL and LDL cholesterol measured at weeks 8, 9, 11, and 12. RESULTS: Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice-treated group compared with the placebo-treated group [(x+/-SD) 6.57+/-0.93 mmol/L (254+/-36 mg/dL) to 5.38+/-0.80 mmol/L (208+/-31 mg/dL); P < 0.001]. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly. CONCLUSIONS: Red yeast rice significantly reduces total cholesterol, LDL cholesterol, and total triacylglycerol concentrations compared with placebo and provides a new, novel, food-based approach to lowering cholesterol in the general population.     

Passive cigarette smoking and reduced HDL cholesterol levels in children with high-risk lipid profiles

BACKGROUND: HDL cholesterol levels are known to be lower in smokers than in nonsmokers. Previous studies have demonstrated an association of decreased HDL cholesterol with passive smoking in children but have not adjusted for potential confounding factors. METHODS AND RESULTS: In a cross-sectional, pilot-scale study, we examined the relationship of HDL cholesterol levels to passive smoking in children and adolescents referred to a tertiary hyperlipidemia clinic. Eligibility criteria included (1) first visit to a lipid clinic, (2) LDL cholesterol >95th percentile for age or HDL cholesterol <5th percentile, (3) age between 2 and 18 years, and (4) absence of secondary causes of hyperlipidemia. Sociodemographic information, diet record, medical history, and fasting lipid profiles were obtained. Of 109 eligible patients, 103 (94%) were studied. Twenty-seven percent came from households with cigarette smokers. HDL cholesterol levels were 38.7+/-1.2 mg/dL (mean+/-SEM) in passive smokers versus 43.6+/-1.2 mg/dL in children without smoke exposure (P=.005). Smoking exposure was not significantly associated with other lipid values. The effect of smoking on HDL cholesterol was minimally affected by potential confounders. In multivariate regression adjusting for body mass index, age, sex, exercise, and dietary fat intake, passive smoking remained a significant risk factor for decreased HDL cholesterol (P=.012). CONCLUSIONS: Mean HDL cholesterol levels are lower in dyslipidemic children from households with smokers than in those without household smoke exposure. Passive smoking may worsen the risk profile for later atherosclerosis among high-risk young persons.     

Hyperlipidaemia in renal transplant patients

OBJECTIVES: The aim of study was to assess the prevalence and severity of hyperlipidaemia in renal transplant patients in a Nordic country. DESIGN: Multicentre, cross-sectional study. SETTING: Outpatients and ward inpatients registered from 23 hospitals covering all regions of the country. SUBJECTS: Renal transplant patients with a functioning graft were registered: 406 patients in all; that is, 43% of the national renal transplant population. All patients used prednisolone, 71% used cyclosporine, either with (51%) or without (20%) azathioprine. Total cholesterol values from general population were obtained from a national survey. MAIN OUTCOME MEASURES: Blood lipids and their relation to clinical parameters. RESULTS: Total cholesterol was significantly higher in transplant patients than in the general population for both genders and all age groups (P < 0.01). Female patients had higher total cholesterol (mean +/- SD: 7.49 +/- 1.61 mmol L(-1)) than males (7.01 +/- 1.55 mmol L(-1); P < 0.001), and also higher HDL cholesterol (1.55 +/- 0.43 vs. males: 1.32 +/- 0.46 mmol L(-1); P < 0.001). Triglycerides were equally elevated in both genders, and 33% had values above 2.2 mmol L(-1). Reduced creatinine clearance, a high body-mass index, female gender, hypertension, and coronary artery disease were independently associated with higher total cholesterol. Beta blockers were associated with lower HDL cholesterol and higher triglycerides, and diuretics with higher triglycerides. Blood lipid levels were not associated with cyclosporine immunosuppression. CONCLUSION: Hyperlipidaemia is prevalent after renal transplantation, and is associated with impaired graft function, hypertension, and with the use of beta blockers and diuretics, but not with the use of cyclosporine.     

Lipoprotein(a) interactions with lipid and nonlipid risk factors in early familial coronary artery disease

An interaction between high plasma lipoprotein(a) [Lp(a)], unfavorable plasma lipids, and other risk factors may lead to very high risk for premature CAD. Plasma Lp(a), lipids, and other coronary risk factors were examined in 170 cases with early familial CAD and 165 control subjects to test this hypothesis. In univariate analysis, relative odds for CAD were 2.95 (P < .001) for plasma Lp(a) above 40 mg/dL. Nearly all the risk associated with elevated Lp(a) was found to be restricted to persons with historically elevated plasma total cholesterol (6.72 mmol/L [260 mg/dL] or higher) or with a total/HDL cholesterol ratio > 5.8. Nonlipid risk factors were also found to at least multiply the risk associated with Lp(a). When Lp(a) was over 40 mg/dL and plasma total/HDL cholesterol > 5.8, relative odds for CAD were 25 (P = .0001) in multiple logistic regression. If two or more nonlipid risk factors were also present (including hypertension, diabetes, cigarette smoking, high total homocysteine, or low serum bilirubin), relative odds were 122 (P < 1 x 10(-12)). The ability of nonlipid risk factors to increase risk associated with Lp(a) was dependent on at least a mildly elevated total/HDL cholesterol ratio. In conclusion, high Lp(a) was found to greatly increase risk only if the total/HDL cholesterol ratio was at least mildly elevated, an effect exaggerated by other risk factors. Aggressive lipid lowering in those with elevated Lp(a) therefore appears indicated.     

Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: results of a meta-analysis

We conducted a meta-analysis to determine the effect of consumption of psyllium-enriched cereal products on blood total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels and to estimate the magnitude of the effect among 404 adults with mild to moderate hypercholesterolemia (TC of 5.17-7.8 mmol/L) who consumed a low fat diet. Studies of psyllium cereals were identified by a computerized search of MEDLINE and Current Contents and by contacting United States-based food companies involved in psyllium research. Published and unpublished studies were reviewed by one author and considered eligible for inclusion in the meta-analysis if they were conducted in humans, were randomized, controlled experiments, and included a control group that ate cereal providing /=50 y) on blood lipids. The meta-analysis showed that subjects who consumed a psyllium cereal had lower TC and LDL-C concentrations [differences of 0.31 mmol/L (5%) and 0.35 mmol/L (9%), respectively] than subjects who ate a control cereal; HDL-C concentrations were unaffected in subjects eating psyllium cereal. There was no effect of sex, age or menopausal status on blood lipids. Results indicate that consuming a psyllium-enriched cereal as part of a low fat diet improves the blood lipid profile of hypercholesterolemic adults over that which can be achieved with a low fat diet alone.     

Effects of lowering average of below-average cholesterol levels on the progression of carotid atherosclerosis: results of the LIPID Atherosclerosis Substudy. LIPID Trial Research Group

BACKGROUND: Cholesterol lowering in patients with above-average cholesterol levels has been shown to reduce the progression of atherosclerosis and lower the risk of coronary heart disease events. However, there has been uncertainty about the effects of cholesterol lowering in patients with average or below-average cholesterol levels. METHODS AND RESULTS: In this study, 522 patients with a history of myocardial infarction or unstable angina and with baseline levels of total cholesterol between 4 and 7 mmol/L (mean, 5.7 mmol/L) were randomized to treatment with a low fat diet plus pravastatin (40 mg daily) or to a low fat diet plus placebo. Treatment with pravastatin reduced the levels of total cholesterol by 19%, LDL cholesterol by 27%, apolipoprotein B by 19%, and triglycerides by 13% (all 2P<.0001) and increased apolipoprotein A1 and HDL cholesterol levels by 4% (both 2P<.0005), in comparison with placebo. Carotid atherosclerosis was assessed from B-mode ultrasound measurements of the common carotid artery. After 4 years, mean carotid wall thickness had increased by 0.048 mm (SE=0.01) in the placebo group and declined by 0.014 mm in the pravastatin-treated group (SE=0.01) (2P for difference <.0001). The effect of treatment on wall thickness was similar in three groups classified by tertiles of total cholesterol at baseline, with mean levels of 4.8, 5.7, and 6.6 mmol/L, respectively (2P for interaction >.8). CONCLUSIONS: Treatment with pravastatin reduced the development of carotid atherosclerosis among patients with coronary heart disease and a wide range of pretreatment cholesterol levels. Treatment with this agent prevented any detectable increase in carotid wall thickening over 4 years of follow-up.     

Cloning and functional expression of a human liver organic cation transporter

OBJECTIVE: The triglyceride-lowering effects of omega-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat (30% total energy) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS: In a controlled, 8-week intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega-3/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate < 100 bpm) exercise program. An oral glucose tolerance test (75 g), fasting serum glucose, insulin, lipids, and GHb were measured before and after intervention. Self-monitoring of blood glucose was performed throughout. RESULTS: In the 49 subjects who completed the study, moderate exercise improved aerobic fitness (VO2max) by 12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age, sex, and changes in body weight, fish diets were associated with increases in GHb (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which were prevented by moderate exercise. CONCLUSIONS: A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise.     

A longitudinal study of work load and variations in psychological well-being, cortisol, smoking, and alcohol consumption

PURPOSE: Although public health interventions have not specifically targeted high density lipoprotein (HDL) cholesterol, observed changes in the prevalence of other cardiovascular risk factors would be expected to have differential effects on HDL. This study examined secular trends in HDL in relation to changes in other cardiovascular risk factors for the years 1981 through 1993 in the Pawtucket Heart Health Program (PHHP) study communities. METHODS: Nonfasting HDL levels were assessed in 12,223 respondents to six biennial population random sample surveys. RESULTS: Between 1981 and 1993, mean HDL cholesterol declined by 0.08 mmol/L in both men and women after adjustment for age, city, education, hormone use, medications, recent alcohol use, smoking, regular exercise, body mass index (BMI), and total cholesterol, (p for trend < 0.001). There was no apparent laboratory explanation for the trend which occurred concurrent with decreased smoking prevalence, increasing BMI and decreased prevalence of recent alcohol use. Decreasing HDL cholesterol was observed consistently across subgroups defined by smoking, alcohol use and BMI. CONCLUSIONS: Although several favorable cardiovascular risk factor trends have been observed in recent decades, declining HDL cholesterol is also of interest, particularly in conjunction with population increases in BMI.     

Effect of dietary fat reduction and increased aerobic exercise on cardiovascular risk factors

1. The combined effect of dietary fat reduction and increased aerobic exercise on coronary heart disease (CHD) risk factors was investigated in healthy, normolipidaemic, normotensive, sedentary individuals. 2. After a baseline period of 2 weeks, 21 subjects were randomly allocated to one of two intervention groups (low fat exercise (LFEX) or low fat control (LFC)) for 8 weeks. Both groups were counselled to reduce their dietary fat intake to 20-25% energy from fat. The LFEX group was also required to commence an aerobic exercise programme (4 x 45 min per week). 3. In both groups, the falls in total cholesterol seen at week 4 were not maintained at the end of the study; however, the LFEX group maintained a fall in low-density lipoprotein (LDL) of 0.21 +/- 0.11 mmol/L. At the end of the study, the LFC group experienced a fall in high-density lipoprotein (HDL)-cholesterol of 0.16 +/- 0.05 mmol/L, due to a 0.19 +/- 0.07 mmol/L fall in the HDL2 subfraction. The LFEX group experienced no change in HDL (-0.09 +/- 0.06 mmol/L) or HDL2 (-0.09 +/- 0.05 mmol/L). 4. At the end of the study the LFEX and LFC groups experienced a 7 +/- 3 and 5 +/- 1 mmHg fall in systolic blood pressure, respectively, while the LFEX group also observed a 4 +/- 2 mmHg fall in diastolic blood pressure. 5. The benefits of a low-fat diet combined with aerobic exercise include a reduction in LDL and blood pressure, while maintaining HDL through the HDL2 subfraction.     

Fetal and maternal lipoprotein metabolism in human pregnancy complicated by type I diabetes mellitus

Serum lipid, apolipoprotein concentration, and lipoprotein composition were determined in maternal and umbilical venous cord blood at delivery by elective Cesarean section (CS) in 10 singleton, full-term pregnancies with maternal insulin-dependent diabetes mellitus (type I DM), which predated pregnancy, and in 22 nondiabetic pregnancies. The objectives of the study were to determine the influence of maternal type I DM, and hence potential fetal overnutrition on fetal lipid metabolism. There were no significant differences in gestational age, fetal weight, or fetal serum insulin concentration between the type I DM group and those with nondiabetic pregnancies, although fetal venous cord blood glucose was 3.4 mmol/L (3.0-4.5 mmol/L) (median and 25th-75th percentiles) and 2.9 mmol/L (2.0-3.4 mmol/L), respectively, and maternal Hemoglobin A1c [9.6% (8.2-10.7%) and 6.8% (6.3-7.8%), respectively], was significantly greater in the type I DM subjects (P < 0.02 and 0.002 respectively). Plasma nonesterified fatty acid (NEFA) concentrations were lower in the type I DM mothers [0.85 mmol/L (0.56-2.31 mmol/L) compared with 1.14 mmol/L (0.88-1.24 mmol/L] in nondiabetic pregnancies; P < 0.0001). Serum high-density lipoprotein phospholipids (HDL-PL) were increased in type I DM mothers because of elevated HDL2 phospholipid [0.39 mmol/L (0.27-0.48 mmol/L) compared with 0.12 mmol/L (0.06-0.21 mmol/L), respectively, P < 0.01). The maternal HDL cholesterol (C) concentration was not significantly different in the uncomplicated and type I DM pregnancies. However, in the umbilical venous cord blood, serum levels of NEFA [0.49 mmol/L (0.33-1.29 mmol/L) in type I DM compared with 0.13 mmol/L (0.06-0.33 mmol/L) in nondiabetics; P < 0.02)], total cholesterol (TC) [2.87 mmol/L (1.65-4.86 mmol/L) in type I DM compared with 1.65 mmol/L (1.46-1.87 mmol/L) in nondiabetics; P < 0.02]; free cholesterol (FC) [0.97 mmol/L (0.60-1.26 mmol/L) in type I DM compared with 0.62 mmol/L (0.37-0.75 mmol/L) in nondiabetics; P < 0.05), and cholesteryl ester (CE) [1.90 mmol/L (1.44-3.33 mmol/L) in type I DM compared with 1.01 mmol/L (0.83-1.24 mmol/L) in nondiabetics; P < 0.02), triglyceride (TG) (1.06 [0.50-1.91) mmol/L in type I DM compared with 0.29 [0.25-0.36] mmol/l in nondiabetics; P < 0.001), phospholipid (PL) (2.52 [1.73-3.03) mmol/L in type I DM compared with 1.34 [1.27-1.48] mmol/L in nondiabetics; P < 0.01], and the apolipoproteins A-I and B had significantly higher concentrations in type I DM. In umbilical venous cord blood, ratios of HDL-TC and HDL-PL to apo AI, reflecting the lipid content of HDL, were reduced when the mother had type I DM during pregnancy (P < 0.02 and P < 0.0001, respectively). These results indicate that maternal type I DM may lead to a fetal serum lipoprotein composition more closely resembling that seen in the adult. In type I DM, maternal TG and PL and fetal TC, TG, PL, CE, and FC were correlated to NEFA levels (P < 0.05), but not to glucose, insulin secretion, or maternal control of type I DM. These data suggest that the enhanced supply of NEFA to the fetus in type I DM pregnancies may drive the synthesis of cholesterol as well as TGs and PLs.     

Insulin sensitivity in familial hypercholesterolemia

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.     

Lipid, apoprotein and fibrinogen levels in the blood of male patients following myocardial infarct and the effect of diet on these parameters in ischemic heart disease

The authors have found significantly higher the levels of two not routinely examined risk factors, fibrinogen and lipoprotein (a) in 28 male patients after myocardial infarction than the corresponding data of the PROCAM-study and in the case of fibrinogen than in 23 healthy blood donors. A positive correlation was observed between the LDL-cholesterol and total cholesterol, the LDL-cholesterol and the main apoprotein of LDL, the Apo B level, and between the HDL-cholesterol and the main apoprotein of HDL, the Apo AI. During a 3 week long treatment in the Cardiac Rehabilitation Department the effect of low cholesterol, high unsaturated fatty acid content diet on the lipid, apolipoprotein and fibrinogen levels of male patients suffering from coronary heart disease with cholesterol level higher than 5.2 mmol/l was studied. Significantly decreased the total cholesterol (from 6.21 +/- 0.96 mmol/l to 5.87 +/- 0.98 mmol/l, -5.5%), the LDL-cholesterol (from 3.87 +/- 1.02 mmol/l to 3.61 +/- 0.96 mmol/l, -6.7%), the HDL-cholesterol (from 1.16 +/- 0.39 mmol/l to 1.04 +/- 0.28 mmol/l, -10.3%), the main apoprotein of HDL, the Apo AI (from 1.47 +/- 0.23 g/l to 1.33 +/- 0.29 g/l, -9.5%) and the main apoprotein of LDL, the Apo B level (from 1.59 +/- 0.43 g/l to 1.46 +/- 0.50 g/l, -8.1%). The change of fibrinogen lipoprotein (a) level was not significant. According to the earlier observation of the authors and the data of the literature, the effect of low cholesterol diet on the change of HDL cholesterol was not favourable. The investigation of apolipoprotein levels failed to get closer to the understanding of its mechanism.     

Stability of lipid/DNA complexes during agitation and freeze-thawing

Among persons with a family history of premature coronary heart disease (CHD), siblings bear an excess risk of CHD that is as high as 12 times that of the general population. Aggressive, new, national guidelines for CHD risk reduction have focused on high-risk families, yet little is known about actual remediable risk factors in siblings of persons with premature CHD. To determine the magnitude of the problem relative to the general population, we screened 846 unaffected siblings (ages 30 to 59 years) of persons with documented CHD before age 60 years and compared their risk factor values with population reference norms obtained in the Third National Health and Nutrition Examination Survey (NHANES III) and the National Health Interview Survey (NHIS). Mean levels of low-density lipoprotein cholesterol were 0.52 mmol/L (20 mg/dl) higher in siblings; the prevalence of low-density lipoprotein cholesterol > or =4.14 mmol/L (160 mg/dl) was nearly twice that of race, sex, and age-specific values from NHANES III. Levels of high-density lipoprotein cholesterol <0.91 mmol/L (35 mg/dl) were similar between siblings and NHANES III (11% and 12%, respectively). Only 4% of all siblings had triglyceride levels > or =4.52 mmol/L (400 mg/dl). Hypertension prevalence was twice as high among siblings as among the NHANES III. Current smoking was 33.9% in white siblings and 25.5% in the NHIS, whereas smoking in African-Americans was similar to that in the NHIS (31.1% vs 29.2%). A mere 13% to 29% of siblings were without any major remediable risk factors. The overwhelming need for risk factor modification in this easily identifiable high-risk population supports aggressive national guidelines and demonstrates the lack of adequate treatment of apparently healthy siblings of persons with premature CHD.     

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.