Modulation of high-density lipoproteins in a population in istanbul, Turkey, with low levels of high-density lipoproteins

The extent to which high-density lipoprotein (HDL) cholesterol levels can be increased in patients with low HDL cholesterol is important because low HDL cholesterol levels increase the risk of coronary heart disease (CHD). During the past 14 years, we have assessed risk factors in Turks, a population in which extremely low HDL cholesterol levels (mean 36 mg/dl in men, 42 mg/dl in women) are a prime CHD risk factor. Although genetically determined to a significant extent, these low HDL cholesterol levels can be modulated by lifestyle factors, as in other populations. We measured the HDL cholesterol levels in men and women residing in Istanbul at 3 time points: 1990 to 1993, 1996 to 2000, and 2003. The mean HDL cholesterol levels increased from 45.3 +/- 9.5 mg/dl in 1990 to 1993 to 49.7 +/- 12 mg/dl in 2003 (p <0.0001) in women, but were virtually unchanged in men (38 +/- 8 vs 39 +/- 10 mg/dl). In contrast to previous years, the HDL cholesterol levels in women in 2003 were markedly affected by education level and socioeconomic status, averaging 56 +/- 9 mg/dl in those with a university education and 48 +/- 12 mg/dl in those with a primary school education. Part of this difference could be explained by less smoking and more exercise and lower body mass index (average 25.6 +/- 4.9 vs 29.7 +/- 5.1 kg/m(2)) of the highly educated women. It is important to note the increase in the prevalence of obesity between the 1990 to 1993 interval and 2003 in men and women, including a remarkable change from 9.4% to 45.2% among women with a primary school education. None of these factors affected the HDL cholesterol levels of men by >2 mg/dl at any of the 3 points. In conclusion, because CHD risk changes by as much as 2% to 4% per 1 mg/dl difference in HDL cholesterol level, the 8 mg/dl difference may reflect as much as a 20% to 30% reduction in CHD risk associated with the benefit of higher education in women. Why education failed to affect the HDL cholesterol levels in Turkish men remains unclear.     

First trimester insulin resistance and subsequent preeclampsia: a prospective study

Insulin resistance is implicated in the pathogenesis of preeclampsia, but prospective data are limited. SHBG, a marker of insulin resistance among nonpregnant individuals, has not been studied in detail during pregnancy. We conducted a prospective, nested, case-control study to test the hypothesis that increased insulin resistance, marked by reduced first trimester SHBG levels, is associated with increased risk of subsequent preeclampsia. First trimester SHBG levels were measured in 45 nulliparous women who subsequently developed preeclampsia (blood pressure, > or =140/90 mm Hg; proteinuria, either > or =2+ by dipstick or > or =300 mg/24 h, after 20 wk gestation) and in 90 randomly selected normotensive nulliparous controls. Compared with controls, women who developed preeclampsia had significantly reduced first trimester SHBG levels (302 +/- 130 vs. 396 +/- 186 nmol/liter; P < 0.01). Every 100 nmol/liter increase in SHBG was associated with a 31% reduced risk of preeclampsia [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.55, 0.88; P < 0.01]. After adjusting for covariates in a multiple logistic regression model, the association between first trimester SHBG and preeclampsia remained significant (per 100 nmol/liter increase; OR, 0.66; 95% CI, 0.47, 0.92; P = 0.01). When subjects were stratified by body mass index (lean: body mass index, < 25 kg/m(2); overweight: body mass index, > or =25 kg/m(2)), overweight women had lower SHBG levels than lean women (286 +/- 156 vs. 410 +/- 166 nmol/liter; P < 0.01), and within each stratum, women with preeclampsia had lower SHBG levels than their respective controls. In a multivariable analysis, the association between SHBG and preeclampsia strengthened among lean women, such that every 100 nmol/liter increase in serum SHBG was associated with a 55% reduction in the risk of preeclampsia (OR, 0.45; 95% CI, 0.27, 0.77; P < 0.01), whereas in overweight women, the association was mitigated (OR, 1.02; 95% CI, 0.62, 1.69; P = 0.9). We conclude that increased early pregnancy insulin resistance is independently associated with subsequent preeclampsia. First trimester SHBG levels may be a useful biomarker for preeclampsia, especially among lean women who otherwise would be perceived to be at low risk.     

A more atherogenic serum lipoprotein profile is present in women with polycystic ovary syndrome: a case-control study

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with a higher frequency of cardiovascular risk factors. Apolipoprotein (apo) A-I and apoB are potent markers for cardiovascular risk. Data on apo levels in women with PCOS are scarce and contradictory. OBJECTIVE: Our objective was to identify changes in lipid metabolism in women with PCOS, and the relative impact of obesity, insulin resistance, and hyperandrogenism on lipid parameters. DESIGN: This was a case-control study. SETTING: The study was performed at a single referral center. SUBJECTS: PCOS was diagnosed according to the 2003 Rotterdam criteria. Healthy mothers with regular menstrual cycles served as controls. MAIN OUTCOME PARAMETERS: Fasting insulin, triglycerides (TGs), cholesterol, high-density lipoprotein (HDL)-cholesterol, apoA-I, and apoB were determined. Low-density lipoprotein (LDL)-cholesterol was calculated using the Friedewald formula. RESULTS: We included 557 women with PCOS and 295 controls. After correction for age and body mass index, PCOS women had higher median levels of insulin (10.1 vs. 6.9 mU/liter), TGs (95 vs. 81 mg/dl), cholesterol (196 vs. 178 mg/dl), and LDL-cholesterol (125 vs. 106 mg/dl) in combination with lower levels of HDL-cholesterol (46 vs. 55 mg/dl) and apoA-I (118 vs. 146 mg/dl) compared with controls (all P values < or = 0.01). apoB levels were similar in cases and controls. Free androgen index, body mass index, SHBG, and estradiol were independent predictors of apoA-I levels in women with PCOS. CONCLUSIONS: PCOS is associated with a more pronounced atherogenic lipid profile. Furthermore, obesity and hyperandrogenism contribute to an adverse lipid profile. Finally, PCOS seems to constitute an additional risk factor for an atherogenic lipid profile.     

Racial disparities in metabolism, central obesity, and sex hormone-binding globulin in postmenopausal women

Increased total and intraabdominal fat (IAF) obesity as well as other metabolic conditions associated with the insulin resistance syndrome (IRS) are related to low levels of sex hormone-binding globulin (SHBG) in young and older Caucasian (CAU) and young African-American (AA) women. We examined whether postmenopausal AA women, a population with a high incidence of obesity and IRS despite low IAF, would have higher levels of circulating SHBG compared with CAU women, and whether there would be negative relationships between indexes of obesity and risk factors associated with IRS and SHBG levels. We measured body composition, SHBG, free testosterone, leptin, glucose tolerance, insulin, and lipoprotein lipids in 55 CAU (mean +/- SD, 59 +/- 7 yr) and 35 AA (57 +/- 6 yr) sedentary women of comparable obesity (48% body fat, by dual energy x-ray absorptiometry). Compared with CAU women, AA women had larger waist (101 vs. 96 cm), larger fat mass (44.9 +/- 8.8 vs. 39.9 +/- 8.1 kg), larger sc fat area (552 +/- 109 vs. 452 +/- 109 cm(2)), and lower IAF/SC ratio (0.28 +/- 0.12 vs. 0.38 +/- 0.15; P < 0.01), but similar waist to hip ratio (0.83). Both groups had similar SHBG (117 vs. 124 nmol/L) and free testosterone (3.7 vs. 3.4 pmol/L) levels, but AA women had a 35% higher leptin, 34% higher fasting insulin, and 39% greater insulin response to a glucose load (P < 0.05) compared with CAU women. In CAU, but not AA, women SHBG correlated negatively with body mass index (r = -0.28; P < 0.05), waist (r = -0.36; P = 0.01), IAF (r = -0.34; P = 0.01), and insulin response to oral glucose (r = -0.37; P < 0.05) and positively with high density lipoprotein cholesterol (r = 0.30; P = 0.03). The relationship between insulin area and SHBG in CAU women disappeared after adjusting for IAF, whereas the relationship between high density lipoprotein cholesterol and SHBG persisted after adjusting for IAF, but not for fat mass. Leptin was positively related to fat mass (P < 0.05) in both groups, but it was related to insulin only in the Caucasian women (P< 0.01). There was a racial difference in the slopes (P< 0.05) of the relationships of leptin to fat mass (P < 0.05). Racial differences in leptin disappeared after adjustment for fasting insulin. These results suggest that the metabolic relationships between total and regional obesity, glucose, and lipid metabolism with SHBG in CAU women are different from those in postmenopausal obese AA women.     

Association of serum apolipoprotein A-I (but not high-density lipoprotein cholesterol) with healed myocardial infarction in men independent of serum insulin and C-peptide

Low serum levels of high-density lipoprotein (HDL) cholesterol or apolipoprotein A-I and high serum levels of insulin increase the risk of coronary heart disease (CHD) and can indicate insulin resistance. We tested the strength, independence, and interactions of associations between HDL cholesterol (or apolipoprotein A-I), insulin (or C-peptide), glucose, and CHD in 95 male nondiabetic patients with CHD who were <60 years old, in 92 probands from the PROCAM study, and in 61 non-cardiologic patients; all subjects were matched by age, body mass index, and smoking habits. Systemic hypertension (odds radio [OR] 2.8, 95% confidence intervals [CI] 1.6 to 4.8), high serum levels of glucose (OR 2.3, 95% CI 1.6 to 4.8), insulin (OR 2.1, 95% CI 1.3 to 3.6), and C-peptide (OR 4.1, 95% CI 2.2 to 7.5) as well as low serum levels of HDL cholesterol (OR 2.0, 95% CI 1.1 to 3.5) or apolipoprotein A-I (OR 3.9, 95% CI 2.1 to 7.1) had significant associations with CHD. At multivariate analysis, systolic blood pressure, glucose, apolipoprotein A-I, and C-peptide, but not HDL cholesterol and insulin, had consistent independent associations with CHD. Thus, the combined measurement of apolipoprotein A-I and C-peptide may improve the identification of nondiabetic patients at increased risk for CHD.     

Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia

Altered angiogenesis and insulin resistance, which are intimately related at a molecular level, characterize preeclampsia. To test if an epidemiological interaction exists between these two alterations, we performed a nested case-control study of 28 women who developed preeclampsia and 57 contemporaneous controls. Serum samples at 12 weeks of gestation were measured for sex hormone binding globulin (SHBG; low levels correlate with insulin resistance) and placental growth factor (PlGF; a proangiogenic molecule). Compared with controls, women who developed preeclampsia had lower serum levels of SHBG (208+/-116 versus 256+/-101 nmol/L, P=0.05) and PlGF (16+/-14 versus 67+/-150 pg/mL, P<0.001), and in multivariable analysis, women with serum levels of PlGF < or =20 pg/mL had an increased risk of developing preeclampsia (odds ratio [OR] 7.6, 95% CI 1.4 to 38.4). Stratified by levels of serum SHBG (< or =175 versus >175 mg/dL), women with low levels of SHBG and PlGF had a 25.5-fold increased risk of developing preeclampsia (P=0.10), compared with 1.8 (P=0.38) among women with high levels of SHBG and low levels of PlGF. Formal testing for interaction (PlGFxSHBG) was significant (P=0.02). In a model with 3 (n-1) interaction terms (high PlGF and high SHBG, reference), the risk for developing preeclampsia was as follows: low PlGF and low SHBG, OR 15.1, 95% CI 1.7 to 134.9; high PlGF and low SHBG, OR 4.1, 95% CI 0.45 to 38.2; low PlGF and high SHBG, OR 8.7, 95% CI 1.2 to 60.3. Altered angiogenesis and insulin resistance are additive insults that lead to preeclampsia.     

Role of small dense low-density lipoprotein in coronary artery disease patients with normal plasma cholesterol levels

OBJECTIVES: The relationship between plasma low-density lipoprotein (LDL) cholesterol and the risk of coronary artery disease (CAD) is known, but the other characteristics of LDL, particularly particle size and density, are unclear. The relationship between small dense LDL phenotype and non-diabetic, normocholesterolemic CAD was investigated in 70 patients with angiographically documented CAD, and 38 age-matched control subjects. METHODS: Peak LDL particle diameter was determined by using 2-16% polyacrylamide gradient gel electrophoresis. Small dense LDL phenotype was defined as particle diameter equal to or less than 255 A. RESULTS: LDL particle diameters in patients with CAD were significantly smaller than those in controls (252.4 +/- 6.9 vs 259.3 +/- 8.8 A, mean +/- SD, p < 0.0001). Prevalence of small dense LDL was markedly higher in patients with CAD (72%) than in subjects without CAD (24%). CAD patients had significantly lower high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels (39.3 +/- 8.8 vs 49.8 +/- 12.0, 108.1 +/- 20.6 vs 122.9 +/- 20.1 mg/dl), and higher lipoprotein (a) and apolipoprotein B levels (28.8 +/- 30.4 vs 16.8 +/- 18.8, 96.5 +/- 21.8 vs 80.2 +/- 14.9 mg/dl) than non-CAD subjects, whereas total cholesterol, LDL-cholesterol, triglyceride, remnant-like particle cholesterol and insulin levels were not increased in CAD patients compared with non-CAD subjects. Stepwise regression analysis revealed that LDL particle size was the most powerful independent determinant of CAD (F value = 20.04, p < 0.0001). Logistic regression analysis revealed that small dense LDL phenotype [relative risk (RR) of 7.0, 95% confidence interval (95% CI) 2.4-20.1], low HDL-cholesterol (RR of 5.6, 95% CI 2.1-15.2), and increased apolipoprotein B (RR of 5.8, 95% CI 1.8-18.5) were independently associated with incidence of CAD. CONCLUSIONS: High prevalence of small dense LDL is a leading cause of CAD with even normal cholesterol levels.     

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease: secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia is primarily implicated in the progression of coronary heart disease (CHD) and its treatment is essential for patients with a history of CHD. Statins such as simvastatin, the lipid-lowering agents, are well-known for their ability to normalize patient's serum lipid levels. The Japan Lipid Intervention Trial study of simvastatin is the first nationwide investigation of the relationship between serum lipid levels and the development of CHD in Japanese patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of coronary events tended to be higher in patients with a serum total cholesterol (TC) > or =240 mg/dl compared with total cholesterol <240 mg/dl. The concentration of low-density lipoprotein cholesterol (LDL-C) positively correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10 mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95% confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A reasonable therapeutic strategy to reduce CHD progression in patients with prior CHD under low-dose statin treatment might be regulating the serum LDL-C concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively.     

High attributable risk of elevated C-reactive protein level to conventional coronary heart disease risk factors: the Third National Health and Nutrition Examination Survey

BACKGROUND: C-reactive protein (CRP), a marker of systemic inflammation, is predictive of coronary heart disease (CHD) events. However, the extent to which high CRP levels (>3 mg/L) may be attributable to high cholesterol levels and other CHD risk factors has not been well defined. METHODS: The prevalence of high CRP levels in the third National Health and Nutrition Examination Survey (n = 15 341) was studied using CHD risk-factor cut points designated as abnormal (total cholesterol values, >or=240 mg/dL [>or=6.22 mmol/L]; fasting blood glucose levels, >or=126 mg/dL [>or=6.99 mmol/L]; blood pressure, >or=140/90 mm Hg; body mass index [BMI], >or=30 kg/m(2); high-density lipoprotein cholesterol values, <40 mg/dL [<1.04 mmol/L] for men and <50 mg/dL [<1.30 mmol/L] for women; triglyceride levels, >or=200 mg/dL [>or=2.26 mmol/L]; current smoking status) or borderline (total cholesterol values, 200-239 mg/dL [5.18-6.19 mmol/L]; fasting blood glucose levels, 100-125 mg/dL [5.55-6.94 mmol/L]; blood pressure, 120-139/80-89 mm Hg; BMI, 25.0-29.9 kg/m(2), and triglyceride values 150-199 mg/dL [1.70-2.25 mmol/L], former smoking status), or normal. RESULTS: Weighted multiple logistic regression analysis demonstrated that high CRP level was significantly more common with obesity (odds ratio [OR], 3.78; 95% confidence interval [CI], 3.28-4.35]), overweight (OR, 1.88; 95% CI, 1.62-2.18), and diabetes (OR, 1.91; 95% CI, 1.54-2.38) and that high CRP level was rare in the absence of any borderline or abnormal CHD risk factor in men (4.4%) and women (10.3%). Overall, the risk of elevated CRP level attributable to the presence of any abnormal or borderline CHD risk factor was 78% in men and 67% women. CONCLUSIONS: These data suggest that elevated CRP levels in the general population are in large measure attributable to traditional CHD risk factors. Moreover, CRP level elevation is rare in the absence of borderline or abnormal risk factors. As such, CRP measurements may have limited clinical utility as a screening tool beyond other known CHD risk factors.     

Aerobic exercise and lipids and lipoproteins in children and adolescents: a meta-analysis of randomized controlled trials

OBJECTIVE: Use the meta-analytic approach to examine the effects of aerobic exercise on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in children and adolescents. STUDY DESIGN: Randomized controlled trials which were limited to aerobic exercise >or=4 weeks in children and adolescents 5-19 years of age. RESULTS: Twelve outcomes representing 389 subjects were available for pooling. Using random-effects modeling, a trend for statistically significant decreases of 12% was found for TG (X +/-S.E.M., -11.0+/-6.1mg/dl; 95% CI, -22.8-0.8 mg/dl) with no statistically significant changes for TC, HDL-C, and LDL-C. Decreases in LDL-C were associated with increased training intensity (r=-0.89; 99% CI, -0.99 to -0.04) and older age (r=-0.90; 99% CI, -0.99 to -0.25) while increases in HDL-C were associated with lower initial HDL-C (r=-0.75; 99% CI, -0.94 to -0.80). Statistically significant decreases in TG were observed in overweight/obese subjects with a trend for increases in HDL-C (TG, X +/-S.E.M., -23.9+/-7.0mg/dl; 95% CI, -37.6 to -10.1mg/dl; HDL-C, X +/-S.E.M., 4.0+/-2.3mg/dl; 95% CI, -0.5-8.5mg/dl). CONCLUSIONS: Aerobic exercise decreases TG in overweight/obese children and adolescents.     

A meta-analysis of the effect of soy protein supplementation on serum lipids

Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.     

Effect of rosiglitazone on insulin resistance, C-reactive protein and endothelial function in non-obese young women with polycystic ovary syndrome

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit elevated levels of serum C-reactive protein (CRP) and impaired endothelium dysfunction which are directly correlated with insulin resistance. Because rosiglitazone improves insulin sensitivity, we tested whether rosiglitazone treatment ameliorates high-sensitivity (hs)CRP levels and endothelial dysfunction in these patients. DESIGN: Thirty-one women with PCOS were recruited (mean age, 24.7+/-3.9 (s.e.) years; mean body mass index (BMI), 25.6+/-3.2 kg/m2). All women were treated with 4 mg rosiglitazone daily for 12 months. METHODS: Serum levels of testosterone, LH, FSH, sex hormone-binding globulin (SHBG), insulin and hsCRP were measured. The BMI, hirsutism scores and insulin sensitivity indices were calculated before and after treatment. Arterial endothelium and smooth muscle function was measured by examining brachial artery responses to endothelium-dependent and endothelium-independent stimuli before and after treatment. RESULTS: After treatment with rosigitazone there were significant decreases in serum testosterone (91.2+/-37.5 vs 56.1+/-21.8 ng/dl; P < 0.01) and fasting insulin concentrations (12.5+/-7.6 vs 8.75+/-4.03 microU/ml; P = 0.015). Insulin resistance indices were significantly improved after rosiglitazone treatment (P < 0.05). There were no significant changes in BMI, waist circumference, serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, FSH and LH levels. Hirsutism score was decreased significantly after treatment (10.8+/-1.8 vs 7.6+/-1.7; P < 0.05). Twenty-four of the women reverted to regular menstrual cycles. Levels of SHBG increased significantly after treatment (28.7+/-8.7 vs 48.4+/-11.2 nmol/l; P < 0.01). Serum hsCRP levels were decreased significantly after rosiglitazone treatment (0.25+/-0.1 vs 0.09+/-0.02 mg/dl; P = 0.006). There was also significant improvement in endothelium-dependent vascular responses after rosiglitazone treatment (9.9+/-3.9 vs 16.4+/-5.1%; P < 0.01). CONCLUSIONS: We conclude that rosiglitazone treatment improves insulin sensitivity in women with PCOS. It also decreases androgen production without significant weight gain. More importantly, it has beneficial effects on endothelial dysfunction and low-grade chronic inflammation in normal weight young women with PCOS.     

Prevalence of low high-density lipoprotein cholesterol in patients with documented coronary heart disease or risk equivalent and controlled low-density lipoprotein cholesterol

Current guidelines identify low-density lipoprotein (LDL) cholesterol as the primary target for cardiovascular prevention but also recognize low high-density lipoprotein (HDL) cholesterol as an important secondary target. This study was conducted to determine the prevalence of low HDL cholesterol in a contemporary ambulatory high-risk population across various LDL cholesterol levels, including patients taking statins. Screening of 44,052 electronic medical records from a primary care practice identified 1,512 high-risk patients with documented coronary heart disease (CHD) or CHD risk equivalents. Low HDL cholesterol (< or =40 mg/dl in men, < or =50 mg/dl in women) was present in 66% of the 1,512 patients. Low HDL cholesterol was prevalent across all LDL cholesterol levels but most prevalent in patients with LDL cholesterol < or =70 mg/dl (79% vs 66% in those with LDL cholesterol 71 to 100 mg/dl and 64% in patients with LDL cholesterol >100 mg/dl, p <0.01). Low HDL cholesterol was equally and highly prevalent in patients taking statins (67%) and those not taking statins (64%) (p = NS). HDL cholesterol and LDL cholesterol levels correlated poorly (R(2) = 0.01), and this was unaffected by gender or statin treatment. In conclusion, in high-risk patients with CHD or CHD risk equivalents, low HDL cholesterol levels remain prevalent despite statin treatment and the achievement of aggressive LDL cholesterol goals.     

Effect of alcohol intake and exercise on plasma high-density lipoprotein cholesterol subfractions and apolipoprotein A-I in women

Abstinence from alcohol consumption for 3 weeks was followed by 3 weeks of wine intake in 18 inactive and 18 physically active premenopausal women (runners). The runners weighed less and had higher plasma high-density lipoprotein (HDL) cholesterol and lower low-density lipoprotein cholesterol levels than the inactive women. There were no differences between groups in plasma total cholesterol, triglyceride and apolipoprotein A-I concentrations. Runners had higher plasma HDL2 cholesterol concentrations than inactive women (34 +/- 17 vs 19 +/- 12 mg/dl), but HDL3 cholesterol concentration did not differ between the groups (41 +/- 10 vs 39 +/- 9 mg/dl). Addition of 35 g/day of ethanol for 3 weeks did not result in a significant change in either group for any of the variables measured. The amount of exercise appears to be a more important determinant of plasma lipoproteins and apolipoprotein A-I than alcohol intake in premenopausal women.     

Lipid changes on hormone therapy and coronary heart disease events in the Heart and Estrogen/progestin Replacement Study (HERS)

Background

Despite the effect of lowering low-density lipoprotein cholesterol (LDL-C) levels and raising high-density lipoprotein cholesterol (HDL-C) levels, combination hormone therapy did not reduce the incidence of coronary heart disease (CHD) events in the Heart and Estrogen/progestin Replacement Study (HERS). To explore possible mechanisms, we examined the association between lipid changes and CHD outcomes among women assigned to hormone therapy.

Methods

HERS participants were postmenopausal women with previously diagnosed CHD who were randomly assigned to receive conjugated estrogens and medroxyprogesterone or identical placebo and then followed-up for an average of 4.1 years. Among women assigned to hormone therapy, associations between baseline-to-year-1 lipid level changes and CHD events were compared with the associations observed for baseline lipids using multivariate proportional hazards models.

Results

Among women assigned to hormone therapy, CHD events were independently predicted by baseline LDL-C levels (relative hazard [RH] 0.94 per 15.6 mg/dL decrease, 95% CI 0.88-1.01) and HDL-C levels (RH 0.89 per 5.4 mg/dL increase, 95% CI 0.81-0.99), but not by triglyceride levels (RH 1.01 per 13.2mg/dL increase, 95% CI 0.97-1.06). CHD events were marginally associated with first-year reductions in LDL-C levels (RH 0.95 per 15.6mg/dL decrease, 95% CI 0.86-1.04), and were not associated with increases in HDL-C levels ( RH 1.03 per 5.4 mg/dL increase, 95% CI 0.91-1.16) or triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.98-1.05).

Conclusion

Changes in lipid levels with hormone therapy are not predictive of CHD outcomes in women with heart disease in the HERS trial.     

Which fasting triglyceride levels best reflect coronary risk? evidence from the turkish adult risk factor study

BACKGROUND: Association between raised low-density lipoprotein cholesterol (LDL-C) levels and high risk for coronary heart disease (CHD) is well established and taken into account in guidelines on coronary prevention. HYPOTHESIS: The relationship between risk for coronary heart disease (CHD) and the levels of fasting plasma triglycerides was studied in the cohort of the Turkish Adult Risk Factor Study, a representative random sample of an adult population. METHODS: In 829 men and 907 women aged > or =27 years (mean 48.5+/-11), plasma lipids and lipoproteins were measured by the enzymatic dry method in the postabsorptive state. A sample of values was validated in a reference laboratory. Apoliprotein (apo) A-I and B were measured by the turbidimetric immunoassay using commercial kits in part of the cohort. Blood pressure and anthropometric measurements were made. Criteria for the diagnosis of CHD were based on history, cardiovascular examination, and Minnesota coding of resting electrocardiograms. Coronary heart disease was diagnosed in about 7% of the subjects. Participants were divided into four categories depending on their triglyceride levels: I = < 100 mg/dl (282 men, 400 women), II = 100-139 mg/dl (204 men, 228 women), III = 140-212 mg/dl (188 men, 180 women), and IV = > or = 212 mg/dl (155 men, 99 women). RESULTS: After adjustment for age, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, smoking, and body mass index by logistic regression analysis, and after assigning the CHD risk of 1 to Category I, the relative risk for men and women combined rose to 1.42 in Category III (p<0.045) while it diminished to 0.94 in Category IV (p = 0.79). In women, the odds ratio (OR) rose gradually up to 1.78 (p< 0.025) in Category III, only to decline in Category IV. The OR in men was slightly, insignificantly, and equally elevated in Categories III and IV. Patients with CHD in Category III were not distinguished from those in Category IV by the studied risk parameters. It was suggested that high risk for CHD--particularly in subjects with slightly elevated or normal cholesterol levels-is often not reflected by extreme increases of fasting triglycerides but best by modest elevations (140-212 mg/dl), which serve better as a marker of triglyceride-rich lipoprotein particles. This knowledge may prove to be of value in population screening and individual risk assessment.     

Prevalence of severe (500 to 2,000 mg/dl) hypertriglyceridemia in United States adults

A growing amount of evidence has supported an association between elevated triglyceride levels and cardiovascular disease. However, little information regarding co-morbidities, levels of other cholesterol types, or medication use among adults with severe hypertriglyceridemia (SHTG; (500 to 2,000 mg/dl) is available. We examined the data from 5,680 subjects, ≥ 20 years old, who had participated in the National Health and Nutrition Examination Survey from 2001 and 2006, to evaluate the epidemiology of adults with SHTG. Approximately 1.7% of the sample had SHTG, equating to roughly 3.4 million Americans. The participants with SHTG tended to be men (75.3%), non-Hispanic whites (70.1%), and aged 40 to 59 years (58.5%). More than 14% of those with SHTG reported having diabetes mellitus, and 31.3% reported having hypertension. Only 14% of the subjects with SHTG reported using statins, and 4.0% reported using fibrates. The factors significantly associated with having SHTG included high-density lipoprotein <40 mg/dl (odds ratio [OR) 11.45, 95% confidence interval [CI] 6.28 to 20.86), non-high-density lipoprotein 160 to 189 mg/dl (OR 9.74, 95% CI 1.68 to 56.40) or non-high-density lipoprotein ≥ 190 mg/dl (OR 24.99, 95% CI 3.90 to 160.31), diabetes mellitus (OR 3.04, 95% CI 1.45 to 6.37), and chronic renal disease (OR 7.32, 95% CI 1.45 to 36.94). In conclusion, SHTG is rare among adults in the United States and the use of pharmacologic intervention is low among those with SHTG.     

Exercise, lipids, and lipoproteins in older adults: a meta-analysis

The authors used the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in adults 50 years of age and older. Twenty-eight outcomes representing 1427 subjects (806 exercise, 621 control) were available for pooling. Random-effects modeling yielded statistically significant improvements of 1.1%, 5.6%, 2.5%, and 7.1%, respectively, for total cholesterol (mean +/- SEM in mg/dL, -3.3+/-1.7; 95% confidence interval [CI], -6.5 to -0.02; p=0.05), high-density lipoprotein cholesterol (2.5+/-1.0; 95% CI, 0.7-4.4; p=0.01), low-density lipoprotein cholesterol (-3.9+/-1.9; 95% CI, -7.7 to -0.08; p=0.05), ratio of total cholesterol to high-density lipoprotein cholesterol (-0.8+/-0.2; 95% CI, -1.2 to -0.4; p<0.001), but not triglycerides (-7.0+/-3.6; 95% CI, -14.0 to 0.1; p=0.06). After conducting sensitivity analyses, only the improvements in high-density lipoprotein cholesterol and the ratio of total cholesterol to high-density lipoprotein cholesterol remained statistically significant (p<0.05 for both). It was concluded that aerobic exercise increases high-density lipoprotein cholesterol and decreases the ratio of total cholesterol to high-density lipoprotein cholesterol in older adults.     

Effect of hospitalization on high-density lipoprotein cholesterol in patients undergoing elective coronary angiography

The effects of time of sampling on plasma lipids and lipoprotein cholesterol concentrations were investigated in 88 patients undergoing elective coronary angiography. Patients with a myocardial infarction or major surgery within 6 weeks before catheterization were excluded. All subjects were sampled in the fasting state at the time of arteriotomy before systemic heparinization and at least 30 days after discharge from the hospital (mean 275 days) in the free living state. No statistically significant differences were noted in total cholesterol (220 +/- 51 vs 226 +/- 48 mg/dl), triglycerides (191 +/- 77 vs 191 +/- 113 mg/dl) and calculated low-density lipoprotein cholesterol levels (149 +/- 46 vs 150 +/- 43 mg/dl). High-density lipoprotein cholesterol values were significantly lower (p less than 0.0001) in subjects sampled before catheterization than in the free living state (32 +/- 10 vs 37 +/- 10 mg/dl, mean change 14%). Moreover, the frequency of high-density lipoprotein cholesterol less than 35 mg/dl was 77% before catheterization and 44% in the free living state. This effect was neither due to beta-adrenergic drugs nor to the length of time between samplings. In view of these findings, a screening lipid profile for patients with coronary artery disease should be performed in the free living state.     

Remnant-like lipoprotein particle level and insulin resistance are associated with in-stent restenosis in patients with stable angina

BACKGROUND: The aim of this study was to evaluate the independent effect of serum remnant-like lipoprotein particle level and insulin resistance on in-stent restenosis in nondiabetic patients with stable angina. METHODS: The study included 64 nondiabetic patients with stable angina who underwent successful coronary stenting. At the time of stenting, we evaluated the patients' lipid profiles including remnant-like lipoprotein particles cholesterol, plasma glucose and insulin levels, and insulin resistance by the homeostasis model assessment. RESULTS: There was no significant difference in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels between two patient groups with (n=15) and without (n=49) in-stent restenosis. Plasma remnant-like lipoprotein particles cholesterol level was significantly higher in patients with restenosis than in patients without restenosis (8.2+/-7.0 mg/dl vs. 4.5+/-2.6 mg/dl, P=0.006). Although plasma glucose level was similar between the two groups, insulin level and homeostasis model assessment were significantly higher in patients with restenosis, compared with those without restenosis (11.2+/-12.4 vs. 7.1+/-2.8, P=0.039; and 2.6+/-2.9 vs. 1.7+/-0.7, P=0.040, respectively). In multivariate logistic regression analysis, plasma remnant-like lipoprotein particles cholesterol level (>4.8 mg/dl; the 75th percentile of the distribution of remnant-like lipoprotein particles cholesterol level) was the independent predictor of in-stent restenosis (odds ratio: 8.15; confidence interval: 1.02-65.16; P=0.048). CONCLUSIONS: Our findings suggest that high serum remnant-like lipoprotein particles cholesterol level, and not insulin resistance may be an independent risk factor on in-stent restenosis in nondiabetic patients with stable angina.