Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study)

International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides for patients at moderately high to high coronary heart disease (CHD) risk. Combination therapy is often required to achieve multiple lipid treatment goals, and > or =50% reduction in low-density lipoprotein cholesterol (LDL-C) is needed in some patients to achieve aggressive LDL-C targets. In this context, we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin (niacin ER), a statin plus ezetimibe, and a highly potent statin alone. This was an open-label, multicenter, 12-week study in 292 patients (50% women) who qualified for drug therapy based on number of CHD risk factors. Patients were randomized to four parallel arms, titrated from low to moderate or high doses: atorvastatin/niacin ER, rosuvastatin/niacin ER, simvastatin/ezetimibe, or rosuvastatin alone. Baseline mean values were, for LDL-C 197 mg/dL (5.1 mmol/L), HDL-C 49 mg/dL (1.3 mmol/L), triglycerides 168 mg/dL (1.9 mmol/L). There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment. All groups lowered LDL-C by approximately 50% or more (range -49 to -57%), achieving mean levels of 82-98 mg/dL (2.1-2.5 mmol/L). Changes in non-HDL-C (range -46 to -55%) mirrored those for LDL-C and did not differ among treatment groups. Statin/niacin ER combination regimens also increased HDL-C and large HDL (HDL2) and lowered triglycerides and lipoprotein (a) significantly more than other regimens. No drug-related myopathy or hepatotoxicity was observed. In this study, low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD.     

Relationships between Smoking Status,Cardiovascular Risk Factors,and Lipoproteins in a Large Japanese Population

Aims: Smoking is a major risk factor for cardiovascular disease (CVD), a leading cause of death and disability. Other CVD risk factors include age, gender, hypertension, diabetes, increased low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C). Our goal was to assess relationships between smoking status and CVD risk factors, with a focus on direct LDL-C, HDL-C, triglycerides (TG) and small dense LDL-C (sdLDL-C). Methods: A total of 34,497 Japanese men and women, mean age 51 years, had their CVD risk factors including fasting serum total cholesterol, TG, HDL-C, sdLDL-C, and direct LDL-C assessed. One-way ANOVA and multiple linear regression analyses were carried to assess the interrelationships of these parameters with smoking. Results: In both men and women, current smokers had significantly ( p ＜0.001) higher median TG (+19.6%, +16.9%) and sdLDL-C levels (+12.7%, +4.2%) levels, and significantly ( p ＜0.001) lower HDL-C levels (-7.3%, -4.3%) than non-smokers. They were also significantly ( p ＜0.05) more likely to have TG values ＞150 mg/dL (+56.8%, +116.3%), sdLDL-C ＞40.1 mg/dL (+28.8%, +44.9%), and HDL-C ＜40 mg/dL (+89.8%, +114.3%). Ex-smokers generally had lipid values that were intermediate between non-smokers and current smokers. Multivariate analysis confirmed the significance of these relationships. Conclusion: Our data indicate that current cigarette smoking is associated with increased TG and sdLDL-C levels, as well as decreased HDL-C levels. Furthermore, smoking effect on lipid profiles remain after cessation. These data provide further justification for smoking cessation.     

Low-density lipoprotein cholesterol: association with mortality and hospitalization in hemodialysis patients

BACKGROUND/AIMS: Hypocholesterolemia is a common finding in hospitalized elderly people, critically ill surgical patients, septic patients and end-stage renal disease patients. The different effect of lipid subfractions on patients with end-stage renal disease has never been demonstrated. We aim to study the effect of lipid subfractions on hospitalization and mortality in maintenance hemodialysis (MHD) patients. METHODS: Lipid subfractions, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured in 210 patients with MHD in a single dialysis center. Patients were stratified into three groups based on the tertiles of lipid levels, and differences in patient characteristics and survival were evaluated. RESULTS: Of a total of 22 deceased patients in our MHD cohort, infection-related mortality (50%) was higher than cardiovascular-related mortality (18.2%). Significant differences (p < 0.05) in the duration and frequency of hospitalization and in mortality events were observed when patients were divided into different subgroups according to the tertiles of baseline TC and LDL-C levels. Patients with lower LDL had significantly lower levels of albumin, TC and TG. The LDL-C tertiles were similar in terms of age, hypertension, diabetes, biochemical results, hematocrit, adequacy of hemodialysis and normalized protein catabolism rate. Both TC and LDL-C predicted survival (p < 0.001), but not TG and HDL-C in the Kaplan-Meier model. The Cox proportional hazard model demonstrated that baseline serum LDL-C was the best lipid subfraction in predicting all-cause death with an adjusted hazard ratio (95% confidence interval) for each 10 mg/dl of 0.752 (0.631-0.898; p = 0.002). CONCLUSIONS: We firstly demonstrated that lipid subfractions, including TC and LDL-C, predict poor outcomes in a MHD cohort with high infection-related mortality.     

Obese children lipid profile: effects of hypocaloric diet and aerobic physical exercise

Diet and exercise help improve obese adults' lipid profile. However, their effect on obese children, the aim of the present study, is poorly known. Fifty obese children were studied into 2 paired groups: Group D (1,500 - 1,800 kcal diet: 55% carbohydrate, 30% fat, 15% protein), and Group DE (same diet + aerobic physical activity 1 hour/day 3 times a week). After 5 months BMI, triglycerides, total cholesterol (TC) and fractions were assessed. No change in triglycerides, TC and low-density lipoprotein cholesterol (LDL-C) levels were reported in both groups. However, high-density lipoprotein cholesterol (HDL-C) increased (+10.3%; p< 0.01) only in DE Group. Screening patients with TC > 170 mg/dL, LDL-C > 110 mg/dL and HDL-C < 35 mg/dL we had: similar reduction for TC in both groups (-6.0% x -6.0%; p= ns), LDL-C reduction in both groups (-14.2% x -13.5%; p= ns), and HDL-C increase only in DE Group (+10.0%; p< 0.05). CONCLUSIONS: 1) Hypocaloric diet (HD) + exercise, rather than diet only, increase obese children's HDL-C levels irrespective of baseline levels; 2) HD only and HD + exercise lead to TC and LDL-C reduction in obese children with TC and LDL-C above normal values.     

Discordance between lipoprotein (a) and LDL-cholesterol levels in cardiovascular risk assessment in apparently healthy subjects

Background and aimsLipoprotein(a) is a recognized independent cardiovascular risk factor and apolipoprotein B (apoB) level better reflects the risk than LDL-cholesterol. Despite this cardiovascular prediction mostly relies on traditional risk factors. We evaluated the association between Lp(a) and lipid biomarkers of cardiovascular risk in relation to age and sex in apparently healthy individuals.Methods and results422 presumably healthy subjects aged 19–84 were included. Lipid profile, Lp(a), apoB and small dense low-density lipoprotein cholesterol (sdLDL-C) were assayed. Subjects were divided at desirable cut-points of apoB and LDL-C. A group with elevated apoB (≥100 mg/dL) at low LDL-C (≤115 mg/dL) was appointed as high-risk and a group with low apoB but elevated LDL-C as low-risk. Significantly elevated triglycerides, TG/HDL-C and sdLDL-C were found in high risk group, but Lp(a) levels were comparable. TG/HDL-C was the best predictor of high risk with a very good diagnostic accuracy (AUC = 0.85), whereas Lp(a) had no discriminatory power. Women aged ≤40 with low LDL-C ≤ 100 mg/dL and elevated Lp(a) ≥ 40 mg/dL had higher levels of apoB and sdLDL-C (p = 0.002; p = 0.07) than those with Lp(a) < 40 mg/dL, which was not observed in men. In young females increase of LDL-C and apoB significantly raised the risk of elevated Lp(a).ConclusionsWomen younger than 40 with low LDL-C may be at increased cardiovascular risk associated with elevated Lp(a) and apolipoprotein B levels. Inclusion of Lp(a) and apoB in the routine lipid testing providing information on an individual level may improve the prediction of cardiovascular risk in primary prevention.     

Study Design, Rationale, and Baseline Characteristics: Evaluation of Fenofibric Acid on Carotid Intima-Media Thickness in Patients with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) Trial

Purpose

Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels contribute to cardiovascular disease risk and can be effectively treated with fenofibric acid. A trial is under way to evaluate the effect of once-daily fenofibric acid or placebo on carotid intima-media thickness (CIMT) progression in patients with controlled low-density lipoprotein cholesterol (LDL-C) levels achieved through atorvastatin treatment, but with high TG and low HDL-C levels.

Methods

In this multicenter, double-blind study, 682 patients were randomized to once-daily delayed-release capsules of choline fenofibrate 135?mg (fenofibric acid [Trilipix?; Abbott, North Chicago, IL]) or placebo plus atorvastatin treatment after a 2- to 10-week diet and atorvastatin run-in period. Key inclusion criteria included age ≥45?years; posterior-wall common CIMT ≥0.7?mm on at least one side at baseline; fasting results of TG ≥150?mg/dL, and HDL-C ≤45?mg/dL for men or HDL-C ≤55?mg/dL for women at screening while receiving atorvastatin; controlled LDL-C; and known coronary heart disease (CHD) or a CHD risk equivalent. The primary efficacy variable is the rate of change from baseline through week 104 in the mean posterior-wall intima-media thickness of the common carotid arteries (composite value of left and right sides).

Conclusions

This trial is the first to examine the effect of fenofibric acid on CIMT and the first CIMT trial to select patients with controlled LDL-C and elevated TG and low HDL-C as inclusion criteria. Also, this trial will prospectively evaluate the effect of treatment on LDL particles and address shortcomings of previous CIMT trials.     

Increased serum lipids are associated with higher CD4 lymphocyte count in HIV-infected women

OBJECTIVE: Highly active antiretroviral therapy (HAART) has been associated with dyslipidaemia; however, the roles of immune status and non-HIV-disease risk factors remain unclear. METHODS: A cross-sectional analysis of fasting lipids was carried out for 231 women, of whom 132 were HIV-infected and 99 were uninfected. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B (apo B) were measured. CD4 lymphocyte count, hepatitis C status, demographics, diet, and anthropometrics were also assessed. RESULTS: A total of 132 women were HIV-infected [30 were antiretroviral-naive, 68 were on protease inhibitors (PIs), and 34 were on non-PI HAART]. HIV infection was associated with higher triglycerides, lower HDL-C, and, among obese women, higher total cholesterol and LDL-C. Non-PI and PI HAART were each independently associated with higher total cholesterol, LDL-C, and apo B, compared with being ART-naive. Among HIV-infected women, after adjustment for HAART use, women with a CD4 lymphocyte count > or =500 cells/microL had total cholesterol 41.8 mg/dL (P = 0.002) and LDL-C 28.8 mg/dL (P = 0.01) higher, on average, than women with a CD4 count <200 cells/microL. Women with a CD4 count of 200-499 cells/microL had total cholesterol 26.31 mg/dL higher, on average, than those with a CD4 count <200 cells/microL (P = 0.04), although differences in LDL-C did not reach significance (15.51 mg/dL; P = 0.12). A higher CD4 count was also associated with higher apo B (P < 0.001). Active hepatitis C infection was associated with lower total cholesterol, LDL-C, triglycerides, and apo B. CONCLUSIONS: Higher CD4 lymphocyte counts were associated with higher lipid levels, suggesting that immune competence may independently affect the dyslipidaemia seen in the HAART era. In addition, it is important that hepatitis C status be assessed in studies of dyslipidaemia in the HIV-infected population.     

Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.     

Lipid response to pioglitazone in diabetic patients: clinical observations from a retrospective chart review

The objective of this study was to determine whether improvements in the lipid profile observed in controlled clinical trials with pioglitazone are seen in the clinical practice setting, and to ascertain the influence of concurrent statin treatment. Charts of 100 consecutive patients with type 2 diabetes (mean age 56.8 years) treated with pioglitazone (45 mg/day) for 2-4 months were retrospectively analyzed for changes in serum lipids, glycemic parameters, and body weight. Subanalyses were performed on the relationship of lipid changes to baseline lipid values and to concurrent statin therapy. Pioglitazone was associated with statistically significant (p < 0.001) changes from baseline in HbA(1C) (mean decrease 1.09%), body weight (mean increase 1.76 kg), HDL cholesterol (HDL-C) levels (mean increase 15.6%), and triglycerides (mean decrease 9.9%). There was an increase (+ 1.09%) in mean individual LDL-C levels from baseline values, but this change was not statistically significant. The greatest absolute and percentage improvements in HDL-C and triglycerides were observed in patients who had the greatest lipid abnormalities at baseline: in patients with baseline HDL-C < 35 mg/dL, mean individual HDL-C values increased by 31% (p < 0.001); in those with baseline triglycerides >399 mg/dL, triglyceride levels decreased by 46% (p < 0.001); and in patients with baseline LDL-C > 129 mg/dL, mean individual LDL-C values decreased by 10.6% (p < 0.001). Subgroup analysis showed similar beneficial changes in HDL-C and triglycerides in patients who were not receiving concurrent statin therapy (n = 48) as in those who were receiving statins (n = 49). This observational study demonstrated that significant improvements in HDL-C and triglyceride levels can be achieved with pioglitazone in the clinical practice setting. The greatest improvements occurred in patients with the worst baseline lipid levels, and benefits were seen regardless of whether patients were receiving concurrent statin therapy.     

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.     

Statin therapy/lipid lowering therapy among Indian adults with first acute coronary event: The dyslipidemia Residual and Mixed Abnormalities IN spite of Statin therapy (REMAINS) study

ObjectiveThe primary objective was to evaluate the effect of statin therapy/lipid lowering therapy (LLT) on lipid profile, in adults presenting with first acute coronary event.Methods and materialA multicentre, observational, prospective cohort study of lipid profiles pre- and post-statin therapy/LLT, among adult patients with confirmed diagnosis of first acute coronary event. The primary outcome measures were low-density lipoprotein cholesterol (LDL-C) in mg/dl, high-density lipoprotein cholesterol (HDL-C) in mg/dl and triglycerides (TG) in mg/dl at baseline and end of study (EOS, 12 weeks [mean: 13.5 weeks]).ResultsTotally 474 patients completed the study. Number of patients with any LDL-C abnormality (LDL-C [all; LDL was abnormal, either alone or along with other lipid parameter(s)]) decreased from 118 (24.9%) to 27 (5.7%), and for LDL-C (only; only the LDL was abnormal), from 46 (9.7%) to 13 (2.7%), both from baseline to EOS. Of 118 patients with high LDL-C (all) at baseline, 91 (77.1%) had reduction in LDL-C to <100 mg/dl, of which 54 (45.8%) had LDL-C <70 mg/dl at EOS. The patients with LDL-C fraction abnormalities decreased, while HDL-C abnormalities increased at EOS from baseline. No major difference was observed at baseline and EOS in levels of TG (all [TG was abnormal, either alone or along with other lipid parameter(s)]) and TG (only [only the TG was abnormal]). Six (1.3%) had seven serious adverse events.ConclusionsThough statin therapy is effective in lowering LDL-C, there still remains residual dyslipidemia, which probably should be tackled with therapeutic and non-therapeutic options.     

The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study

OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults. DESIGN: A prospective population-based study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later. MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality. CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.     

Baseline lipid values partly determine the response to high-dose simvastatin in patients with familial hypercholesterolemia. The examination of probands and relatives in Statin studies with familial hypercholesterolemia (ExPRESS FH)

Statins decrease low-density lipoprotein cholesterol (LDL-C), and additionally, reduce triglycerides (TG) and raise high-density lipoprotein cholesterol (HDL-C) levels. This study evaluated the frequency of abnormal TG and HDL-C levels in patients with classical familial hypercholesterolemia (FH) and assessed therapeutic response at different baseline levels of these lipoproteins after 1 year of statin therapy. A total of 508 FH patients were included and mean LDL-C levels (8.37+/-2.12 mmol l(-1)) were severely elevated. After a washout period of 6 weeks, all patients started monotherapy with 80 mg simvastatin. Remarkably, LDL-C reduction was dependent on baseline LDL-C levels ranging from 51.1 to 45.5% in the top versus the bottom third of the LDL-C distribution. Unexpected in FH, elevated baseline TG levels were seen in 30% and low HDL-C levels in 15% of all patients. Also, changes in these lipoproteins were dependent on baseline levels; TG reduction was 40.7 versus 22.2% in patients with elevated versus normal levels, while HDL-C increase was 29.1 versus 11.4% in patients with low versus normal HDL-C levels. In conclusion, FH patients with the worst lipoprotein profile showed the greatest benefit from high-dose simvastatin treatment, since changes in these parameters were partly determined by baseline lipid levels.     

Can Group Medical Clinics Improve Lipid Management in Diabetes?

Background

Group medical clinics may improve diabetes and hypertension control, but data about dyslipidemia are limited. We examined the impact of group medical clinics on lipids among patients with uncontrolled diabetes and hypertension.

Methods

Prespecified secondary analysis of 239 veterans randomized to group medical clinics or usual care. Lipids were assessed at study baseline, midpoint, and end. We used linear mixed models to compare lipid levels between arms and generalized estimating equation models to compare low-density lipoprotein cholesterol (LDL-C) goal attainment. An additional post hoc analysis examined intensification of cholesterol-lowering medications in both arms.

Results

At baseline, mean total cholesterol was 169.7 mg/dL (SD 47.8), LDL-C 98.2 mg/dL (SD 41.7), and high-density lipoprotein cholesterol (HDL-C) 39.3 mg/dL (SD 13.0). Median baseline triglycerides were 131 mg/dL (interquartile range 122). By study end, mean total cholesterol and LDL-C in group medical clinics were 14.2 mg/dL (P = .01) and 9.2 mg/dL (P = .02) lower than usual care, respectively; 76% of group medical clinic patients met goals for LDL-C, versus 61% of usual care patients (P = .02). Triglycerides and HDL-C remained similar between study arms. Treatment intensification occurred in 52% of group medical clinic patients, versus 37% of usual care patients between study baseline and end (P = .04). The mean statin dose was higher in group medical clinic patients at study midpoint and end.

Conclusions

Group medical clinics appear to enhance lipid management among patients with diabetes and hypertension. This may be a result of greater intensification of cholesterol-lowering medications in group medical clinics relative to usual care.     

What is the consequence of an abnormal lipid profile in patients with type 2 diabetes or the metabolic syndrome?

Patients with type 2 diabetes have an atherogenic lipid profile, which greatly increases their risk of coronary heart disease (CHD) compared with people without diabetes. The largest disparity in lipid levels among people with and without diabetes occurs for high-density lipoprotein cholesterol (HDL-C) and triglycerides: triglycerides tend to be markedly higher and HDL-C moderately lower in patients with diabetes, in contrast to the negligible difference observed in low-density lipoprotein cholesterol (LDL-C) and total cholesterol. However, patients with type 2 diabetes are more likely to have the atherogenic form of LDL-C than people without diabetes, as well as low HDL-C, which restricts reverse cholesterol transport and may also be associated with increased lipid oxidation. Among patients who have suffered a myocardial infarction, increased LDL-C is apparent in early adulthood, whereas a detectable difference in HDL-C levels becomes increasingly apparent with age and most pronounced after age 60 years, compared with healthy controls. Evidence indicates that the increased risk of macrovascular complications of type 2 diabetes begins long before the onset of clinical hyperglycaemia. Despite successful reduction of LDL-C with statin therapy, patients continue to be at increased risk for CHD if their HDL-C levels remain suboptimal, in part due to persistence of enhanced lipid exchange. Observational data suggest that increasing HDL-C should be much more potent therapeutically than a similar proportionate decrease in LDL-C.     

Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome.

PURPOSE: Women with polycystic ovary syndrome are hyperandrogenemic and insulin resistant, which are associated with alterations in circulating lipid and lipoprotein levels. We sought to determine the prevalence of, and risk factors for, lipid abnormalities in these women. SUBJECTS AND METHODS: Non-Hispanic white women with polycystic ovary syndrome (n = 195) and ethnically matched control women (n = 62) had fasting blood obtained for hormone and lipid levels. Subjects were categorized by body mass index (nonobese <27 kg/m(2), obese > or =27 kg/m(2)), and analyses were adjusted for age. RESULTS: Total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels increased significantly in obese women with polycystic ovary syndrome (n = 153) compared with obese control women (n = 35; mean difference in total cholesterol level = 29 mg/dL; 95% confidence interval [CI]: 14 to 45 mg/dL; P <0.001; mean difference in LDL-C level = 16 mg/dL; 95% CI: 4 to 30 mg/dL; P = 0.006). Similarly, total cholesterol and LDL-C levels increased significantly in nonobese women with polycystic ovary syndrome (n = 42) compared with nonobese control women (n = 27; mean difference in total cholesterol = 32 mg/dL; 95% CI: 13 to 52 mg/dL; P <0.001; mean difference in LDL-C level = 32 mg/dL; 95% CI: 15 to 52 mg/dL; P <0.001). In obese women, high-density lipoprotein cholesterol (HDL-C) and triglyceride levels increased significantly in women with polycystic ovary syndrome compared with control women (mean difference in HDL-C level = 6 mg/dL; 95% CI: 2 to 12 mg/dL; P = 0.002; mean difference in triglyceride level = 34 mg/dL; 95% CI: 1 to 77 mg/dL; P = 0.04). Differences in LDL-C and HDL-C levels, but not triglyceride levels, remained significant after adjusting for alcohol intake, smoking, and exercise. Although age, body mass index, and polycystic ovary syndrome status were significant predictors of lipid levels, these factors accounted for no more than 25% of the variance. CONCLUSIONS: In this large study of non-Hispanic white women, elevations in LDL-C levels were the predominant lipid abnormality in women with polycystic ovary syndrome, independent of obesity. The characteristic dyslipidemia of insulin resistance was absent. Indeed, obese women with polycystic ovary syndrome had relatively elevated HDL-C levels, which may confer some protection against cardiovascular disease.     

The evolving role of high-density lipoprotein in reducing cardiovascular risk

In many patients with coronary artery disease, a low level of high-density lipoprotein cholesterol (HDL-C), rather than substantially elevated lowdensity lipoprotein cholesterol (LDL-C), is often the predominant lipid abnormality. Although the National Cholesterol Education Program treatment guidelines include HDL-C concentration as a major risk factor for primary prevention, the guidelines' emphasis on LDL-C as the primary target of therapy may cause uncertainty as to whether risk reduction strategies should focus on lowering LDL-C or raising HDL-C in high-risk patients with low HDL-C. Recent clinical trial evidence and epidemiologic data suggest that HDL-C should play a more important role in risk assessment, and that the definition of low HDL-C may need adjustment from the current National Cholesterol Education Program definition of <35 mg/dL to perhaps <40 mg/dL in men and <45 mg/dL in women. Patients with low HDL-C should receive aggressive risk factor modification, and more emphasis on increasing HDL-C may be warranted in addition to lowering LDL-C.     

Plasma fasting and nonfasting triglycerides and high-density lipoprotein cholesterol in atherosclerotic stroke: Different profiles according to low-density lipoprotein cholesterol

Although low-density lipoprotein cholesterol (LDL-C) is the main lipid target for cardiovascular risk reduction, recent studies suggest that other lipid indicies are also associated with vascular events. We hypothesized that the association of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) with atherosclerotic stroke (AS) differs depending on LDL-C levels. Data prospectively collected on subjects admitted with acute ischemic stroke to a university medical center were analyzed. We divided the patients into AS and non-atherosclerotic stroke (NAS) groups and independent association of lipid parameters and genetic influences of apolipoprotein A5 (ApoA5) polymorphisms with AS were evaluated. Of 268 patients, 160 (59.7%) were classified with AS and 108 (40.3%) were classified with NAS. Vascular risk factors were more prevalent in AS patients than in those with NAS; additionally, AS patients' anthropometric indexes and laboratory findings showed that they were prone to atherosclerosis. AS was independently associated with fasting TG (OR per 10 mg/dL increase, 1.38; 95% CI, 1.16–1.64; OR for highest vs. lowest tertile, 12.85; 95% CI, 3.31–49.85), HDL-C (OR per 10 mg/dL increase, 0.61; 95% CI, 0.42–0.88; OR for lowest vs. highest tertile, 4.28; 95% CI, 1.16–15.86), and nonfasting TG (OR per 10 10 mg/dL increase, 1.25; 95% CI, 1.11–1.42; OR for highest vs. lowest tertile, 8.20; 95% CI, 1.98–33.88) only among patients with LDL <100 mg/dL. No interaction was observed between fasting and nonfasting TG and ApoA5 polymorphisms. In conclusion, fasting and nonfasting TG and HDL-C were associated with AS only when patients had low levels of LDL-C. Non-LDL-C may have an additional role in addition to the LDL-C levels in AS development.     

Long-Term Efficacy of Adding Fenofibric Acid to Moderate-Dose Statin Therapy in Patients with Persistent Elevated Triglycerides

Objective

The objective of this study was to evaluate the long-term efficacy of adding fenofibric acid to moderate-dose statin therapy in patients at goal for low-density lipoprotein cholesterol (LDL-C) but with persistent hypertriglyceridemia.

Methods

This is a post hoc analysis of a subset of patients (N?=?92) with mixed dyslipidemia treated with moderate-dose statin (rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg) for 12 weeks in three controlled trials who had achieved LDL-C <100 mg/dL but whose triglycerides remained >200 mg/dL, and had fenofibric acid 135 mg added to the moderate-dose statin in a 52-week open-label extension study. Lipid and apolipoprotein (Apo) values and the proportion of patients meeting individual and combined treatment targets with combination therapy were determined at scheduled visits during the 52-week study and compared with baseline (start of extension study).

Results

Addition of fenofibric acid to moderate-dose statin for 52 weeks resulted in significant (P?P?=?0.007), and LDL-C?+?non–HDL-C?+?ApoB?+?HDL-C?+?triglycerides (25.6% vs 0.0%) than at baseline.

Conclusions

The addition of fenofibric acid to moderate-dose statin in patients whose LDL-C was optimal but whose triglycerides remained >200 mg/dL led to additional improvements in non–HDL-C, ApoB, HDL-C, and triglycerides that resulted in greater proportions of patients attaining optimal levels of the individual parameters as well as simultaneously achieving optimal levels of these parameters and LDL-C.

     

Risk determination of dyslipidemia in populations characterized by low levels of high-density lipoprotein cholesterol

Background

Current guidelines for managing dyslipidemia qualify patients for treatment based on low-density lipoprotein cholesterol (LDL-C) levels and other risk factors for coronary heart disease (CHD). However, when LDL-C is the sole lipid criterion for initiating therapy, patients with levels below the treatment initiation threshold who are at high risk because of low levels (<40 mg/dL) of high-density lipoprotein cholesterol (HDL-C) might not be identified. Twenty percent of male patients with CHD in the United States fall into this category. The total cholesterol/HDL-C (TC/HDL-C) ratio predicts CHD risk regardless of the absolute LDL-C and HDL-C.

Methods

We compared guidelines based on TC/HDL-C and LDL-C with those recommended by the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Both sets of guidelines were applied to 9837 adults (>20 years of age) in the Turkish Heart Study, which has shown that 75% of men and 50% of women in Turkey have HDL-C <40 mg/dL.

Results

ATP III guidelines identified 14% of Turkish adults, 20 years or older, as candidates for lifestyle treatment only and an additional 18% for drug treatment. In conjunction with ATP III LDL-C thresholds, the TC/HDL-C ratio (>3.5, patients with CHD; ≥6.0, 2+ risk factors, ≥7.0, 0 to 1 risk factor) assigned lifestyle therapy alone to 18% and drug treatment to an additional 36%. Among primary prevention subjects at high risk because of age (men ≥45 years; women ≥55 years), both sets of guidelines prescribed lifestyle therapy for only 5%; however, drug treatment was recommended for an additional 13% by ATP III guidelines and an additional 18% by TC/HDL-C and LDL-C.

Conclusions

In populations at risk for CHD caused by low HDL-C, qualification of subjects for treatment based on either the TC/HDL-C ratio or LDL-C thresholds identifies more high-risk subjects for treatment than LDL-C threshold values alone, and use of the ratio, instead of risk tables, simplifies the approach for physicians.