Efficacy and safety of the intensive dose of rosuvastatin 40 mg/day in patients with acute coronary syndrome and at high risk of cardiovascular disease-ROSUVEES-2

BackgroundRandomized clinical trials have established the benefits of statin therapy in acute coronary syndromes (ACS) via their pleiotropic effects.Aim of the studyThis was a 12-week, open-label, multicenter, postmarketing observational study evaluating the efficacy and safety of rosuvastatin 40 mg/day in very high-risk or high-risk Indian patients according to NCEP ATP III guidelines.MethodologyOne hundred and sixty two patients (age: 30 to 69 years) with evidence of coronary artery disease, hospitalized with chest pain with/without electrocardiogram changes and with non-ST segment elevation ACS and ST segment elevation ACS who received optimal reperfusion therapy were enrolled. The primary endpoint was the percent change from baseline in low-density lipoprotein cholesterol (LDL-C) levels at 6 and 12 weeks of treatment. Other lipid parameters, high sensitive C-reactive protein (hsCRP), glycosylated hemoglobin, and clinical biochemical parameters were also assessed.ResultsAt 12 weeks, intensive therapy with rosuvastatin 40 mg/day significantly reduced LDL-C (p < 0.001), total cholesterol (TC) (p < 0.001), triglyceride (p < 0.01), TC/high density lipoprotein cholesterol (HDL-C) ratio (p < 0.001), non-HDL-C (p < 0.001), LDL-C/HDL-C ratio (p < 0.001), and hsCRP (p = 0.034) in very high-risk and high–risk patients with ACS. Overall, 54.5% (61/112) patients achieved LDL-C goal of <70 mg/dL. However, the change in HDL-C and very low density lipoprotein cholesterol (VLDL-C) were not significant. Few adverse events including myalgia were reported during the study.ConclusionResults of this study showed that 40 mg dose of rosuvastatin, initiated early and continued for 12 weeks, was effective in terms of reducing LDL cholesterol and was well tolerated.     

High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: a systematic review

Background and purposeEpidemiological studies have found no relationship between total cholesterol and stroke risk, but little attention has been paid to high-density lipoprotein-cholesterol (HDL-C).MethodsWe performed a systematic PubMed literature search for epidemiological studies that examined the association between HDL-C level and stroke or carotid intima-media thickness (IMT).ResultsWe identified 18 studies on the relationship between HDL-C and stroke risk and 37 on HDL-C and carotid IMT. Eight of ten prospective cohort studies (n = 238 739) and three of eight case–control studies (n = 3604 cases, 8220 controls) supported an association between elevated HDL-C level and decreased risk of stroke. Prospective cohort studies reporting on relative risk per unit increase in HDL-C showed an 11–15% decreased stroke risk per 10-mg/dl increase in HDL-C. Of 37 studies on carotid IMT, 31 reported cross-sectional, one longitudinal, and five both cross-sectional and longitudinal associations between HDL-C level and carotid IMT. Of 36 cross-sectional studies (n = 51 288), 20 showed an inverse association between HDL-C level and carotid IMT. Of six longitudinal studies (n = 20 065), three showed no association, one showed a weak association in a subgroup of white women and two showed a significant inverse relationship between HDL-C level and carotid IMT. Pooled estimates could not be calculated because of the variation in study designs and analysis.ConclusionsThe weight of evidence in the literature supports an inverse association between HDL-C level and stroke or carotid atherosclerosis, but more data are needed to firmly establish this protective effect.     

Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients

ObjectiveTo study the effects of HIV-infection and protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) on the lipid and high-density lipoprotein (HDL) subpopulation profile and to relate the changes to coronary heart disease (CHD)-risk.Methods and designThe lipid and HDL subpopulation profiles of HIV-positive subjects (n = 48) were studied prospectively by comparing pre- and post-PI-HAART data as well as cross-section by comparing the profiles to HIV-negative subjects with (n = 96) and without CHD (n = 96).ResultsHIV-infected HAART-naïve subjects had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and HDL-C and higher concentration of triglycerides (TG) than healthy controls. After receiving PI-based HAART, LDL-C and TG concentrations increased, while HDL-C concentrations remained unchanged. The HDL subpopulation profiles of HAART-naïve HIV-positive patients were significantly different from those of healthy controls and were similar to those with CHD. Moreover, the HDL subpopulation profile changed unfavorably after PI-based HAART, marked with increased concentrations of the small, lipid-poor pre-β-1 HDL (32% or 3.9 mg/dl; p < 0.001), and decreased concentration of the large, cholesterol-rich α-1 HDL(9% or 1 mg/dl ns).ConclusionAn already unfavorable lipid and HDL subpopulation profile of HIV-positive HAART-naïve subjects further deteriorated after receiving PI-based treatment, which may cause increased CHD-risk in these subjects.     

Coronary calcification is more predictive of carotid intimal medial thickness in black compared to white middle aged men

BackgroundRace-specific data for the association between coronary artery calcification (CAC) and carotid intimal medial thickness (IMT) are limited. We sought to compare black-white specific associations of these two measures.MethodsWe conducted a population-based study of 379 randomly selected men aged 40–49 years (84 black and 295 white) from Allegheny County, US (2004–2006). Agatston CAC score was evaluated by electron-beam tomography and carotid IMT was evaluated by ultrasonography.ResultsCompared to white men, black men had similar prevalence of CAC (p = 0.56) and higher total carotid IMT (p < 0.001). In black and white men, CAC score had significant positive correlations with total carotid IMT (r = 0.47 and r = 0.24, respectively, p < 0.001 for both) as well as the IMT for the common carotid artery (CCA), internal carotid artery and carotid bulb. The associations of CAC with total and CCA IMT were significantly stronger in black (β = 0.07 and β = 0.05, respectively) than white men (β = 0.03 and β = 0.01, respectively) after adjustment for traditional coronary risk factors (p = 0.046 and p = 0.036, respectively).ConclusionsIn black and white middle aged men, CAC score had significant positive correlations with total and segmental carotid IMT. CAC was more predictive of total and CCA IMT in black than white men independent of coronary risk factors.     

Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials

ObjectivePatients with dyslipoproteinemia constitute the largest risk group for development of atherosclerosis and cardiovascular disease (CVD). Despite extensive statin use, many patients with CVD risk do not achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets. This pooled analysis of 27 previously published clinical trials conducted between 1999 and 2008 evaluated the lipid-altering efficacy and factors related to treatment response of ezetimibe combined with statin and statin monotherapy.MethodsPatient-level data were combined from double-blind, placebo-controlled or active comparator studies randomizing adult subjects to ezetimibe 10 mg plus statin (n = 11,714) versus statin alone (n = 10,517) for 6–24 weeks (mean = 9 weeks). Association of factors with treatment response, percent change from baseline LDL-C and other lipids, and attainment of guideline-recommended lipid and lipoprotein targets were evaluated.ResultsHigher baseline LDL-C, diabetes mellitus, Black race, greater age, and male gender were associated with small but significantly greater percent reductions in LDL-C regardless of treatment. Treatment influenced efficacy, with ezetimibe plus statin producing significantly greater reductions in LDL-C, total-cholesterol, non-HDL-C, ApoB, triglycerides, lipid ratios, hs-CRP; significantly larger increases in HDL-C and ApoA1; and significantly higher achievement of LDL-C (<70 mg/dl, <100 mg/dl), non-HDL-C (<100 mg/dl, <130 mg/dl), and ApoB (<80 mg/dl, <90 mg/dl) targets than statin monotherapy at statin potencies compared (p < 0.0001 for all). Differential treatment effects were seen with first-/second-line therapy and statin potency.ConclusionThese results suggest that patient characteristics have a limited influence on response to lipid-lowering therapy and demonstrate the consistent treatment effect of ezetimibe combined with statin and statin monotherapy across a diverse patient population.     

Intima-media thickness is a useful marker of the extent of coronary artery disease in patients with impaired renal function

ObjectiveThe aim of the study was the assessment of intima-media thickness (IMT) in peripheral arteries (the carotid and the femoral artery) and its correlation with the extent of coronary artery disease (CAD). The second task was the analysis of the renal function's influence within IMT complex.Methods231 patients (men, mean age 52.8), who had undergone coronary angiography due to symptoms of CAD were enrolled. The ultrasound measurement of IMT in the common carotid artery (CCA), carotid bulb and common femoral artery (CFA) was performed. The relationship between IMT, renal function and the extent of CAD was evaluated.ResultsSignificantly higher values of IMT in the peripheral arteries were observed in patients with CAD than in those without (CCA—0.91 vs 0.61 mm, carotid bulb—1.31 vs 0.67, CFA—1.38 vs 0.63 respectively, p < 0.0001). The GFR values in the CAD patients significantly negatively correlated with IMT complex in CCA (p < 0.001) and carotid bulb (p < 0.05). Lower values of GFR in patients with three-vessel disease were observed than in those patients with one- or two-vessel disease (p < 0.05). In multifactoral analysis (post-hoc NIR test) we found that glomerular filtration rate (GFR) is strongly determined by age (p < 0.0001), BMI (p < 0.0001), value of carotid intima-media thickness (p < 0.001), value of IMT in the carotid bulb (p < 0.02) and the treatment with ACE-I (p < 0.05). In multifactoral analysis we did not find any statistical influence of lipid profile and glucose disturbances on GFR.ConclusionsHigher peripheral artery IMTs in patients with CAD than in those without and patients with three-vessel disease indicate that IMT may be used as an early marker of atherosclerosis and reflect the severity of CAD. A significant negative correlation between the value of a GFR and the IMT confirmed the usefulness of this noninvasive method for the estimation of preclinical stages of atherosclerotic changes’ development in patients with impaired renal function.     

Inflammation modulates human HDL composition and function in vivo

ObjectivesInflammation may directly impair HDL functions, in particular reverse cholesterol transport (RCT), but limited data support this concept in humans.Methods and resultsWe employed low-dose human endotoxemia to assess the effects of inflammation on HDL and RCT-related parameters in vivo. Endotoxemia induced remodelling of HDL with depletion of pre-β1a HDL particles determined by 2-D gel electrophoresis (?32.2 ± 9.3% at 24 h, p < 0.05) as well as small (?23.0 ± 5.1%, p < 0.01, at 24 h) and medium (?57.6 ± 8.0% at 16 h, p < 0.001) HDL estimated by nuclear magnetic resonance (NMR). This was associated with induction of class II secretory phospholipase A2 (～36 fold increase) and suppression of lecithin:cholesterol acyltransferase activity (?20.8 ± 3.4% at 24 h, p < 0.01) and cholesterol ester transfer protein mass (?22.2 ± 6.8% at 24 h, p < 0.001). The HDL fraction, isolated following endotoxemia, had reduced capacity to efflux cholesterol in vitro from SR-BI and ABCA1, but not ABCG1 transporter cell models.ConclusionsThese data support the concept that “atherogenic-HDL dysfunction” and impaired RCT occur in human inflammatory syndromes, largely independent of changes in plasma HDL-C and ApoA-I levels.     

Association between traditional cholesterol parameters, lipoprotein particle concentration, novel biomarkers and carotid plaques in retired National Football League players

ObjectivesWe assessed whether low-density lipoprotein particle concentration (LDL-P) and high-sensitivity C-reactive protein [hs-CRP] can identify subclinical atherosclerosis better than traditional cholesterol parameters in retired National Football League (NFL) players.BackgroundIt is not known whether LDL-P and the biomarker hs-CRP can identify subclinical atherosclerosis better than low-density lipoprotein cholesterol (LDL-C) or non-high-density-lipoprotein cholesterol (non-HDL-C) in retired NFL players, given high prevalence of metabolic syndrome in these players.MethodsCarotid artery plaque screening was performed with traditional lipids, LDL-P, and hs-CRP in 996 retired players. Logistic regression analyses comparing highest with the lowest quartile were performed.ResultsCarotid artery plaques were seen in 41%. LDL-C (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.06–2.59), non-HDL-C (OR 1.67, 95% CI 1.04–2.67), and LDL-P (OR 2.21, 95% CI 1.35–3.62) were associated with plaques in adjusted models. Among 187 retired players with metabolic syndrome, LDL-C (OR 1.40, 95% CI 0.53–3.72) was not associated with carotid plaques, whereas LDL-P (OR 3.71, 95% CI 1.16–11.84) and non-HDL-C (OR 2.63, 95% CI 0.91–7.63, p = 0.07; borderline significant) were associated with carotid plaques. hs-CRP (OR 1.13, 95% CI 0.71–1.79) was not associated with carotid plaques.ConclusionCarotid artery plaques were common in retired NFL players and were strongly associated with LDL-P, especially among those with metabolic syndrome. hs-CRP was not associated with carotid plaques in this cohort.     

High plasma HDL-C attenuates stress hyperglycemia during acute phase of myocardial infarction

ObjectiveDuring myocardial infarction (MI), a transient decrease of both insulin sensitivity and secretion triggers stress hyperglycemia, which is followed by a substantial increase in mortality. Recent findings in cellular models indicate that HDL may act on glucose homeostasis by improving insulin sensitivity and secretion. In this study, we explored this potential effect in patients during the acute phase of MI.MethodsPlasma glucose, insulin and C-peptide were measured at admission in the first 24 h and on the fifth day after MI with ST-segment elevation in 183 consecutive non-diabetic patients. Patients were divided into HDL-C quartiles for the analyses (Q1: <31, Q2: 31–38, Q3: 38–47 and Q4: >47 mg/dL). The Homeostasis Model Assessment version 2 was used to assess insulin sensitivity (HOMA2S) and beta-cell function (HOMA2B).ResultsOn admission, no difference was found between the quartiles in glucose (p = 0.6), insulin (p = 0.6) or C-peptide (p = 0.5) levels, HOMA2S (p = 0.9) or HOMA2B (p = 1.0). On the fifth day there was a reduction in glucose levels whose intensity was directly proportional to the HDL-C quartile (p < 0.001). At the same time, there was a reduction in plasma insulin (p < 0.001) and C-peptides (p < 0.001) whose magnitude was inversely proportional to the HDL-C quartile. Consistently, the increase of HOMA2S (p < 0.001) and HOMA2B (p = 0.01) were also positively associated with HDL-C levels. Furthermore, plasma HDL-C levels were inversely and independently associated with blood glucose change during the acute phase.ConclusionThis study demonstrates the association between low plasma HDL-C levels and increased duration of stress hyperglycemia during MI and suggests in humans the interaction between HDL and insulin secretion and sensitivity.     

Follow-up association study of linkage regions reveals multiple candidate genes for carotid plaque in Dominicans

BackgroundIt has been well established that cilostazol has anti-proliferative effect against in-stent restenosis. However, it remains unclear whether cilostazol can prevent the progression of carotid atherosclerosis.Methods and resultsWe performed a meta-analysis of all relevant randomized controlled trials (RCTs) to evaluate the effect of cilostazol on the progression of carotid intima-media thickness (IMT). Five RCTs with 698 patients [597 subjects with type 2 diabetes mellitus (T2DM)] were included in this study. Cilostazol was associated with a significant reduction in the progression of carotid IMT (WMD, ?0.08 mm, 95% CI ?0.13, ?0.04; P = 0.00003). Subgroup analysis shows that cilostazol monotherapy or addition to dual antiplatelet therapy (aspirin and clopidogrel) was superior to placebo (WMD, ?0.04 mm, 95% CI ?0.05, ?0.03; P < 0.00001), no antiplatelet medication (WMD, ?0.12 mm, 95% CI ?0.21, ?0.03; P = 0.008), aspirin monotherapy (WMD, ?0.06 mm, 95% CI ?0.12, 0.00; P = 0.04) or dual antiplatelet therapy (WMD, ?0.16 mm, 95% CI ?0.30, ?0.02; P = 0.03) in preventing the progression of carotid IMT. Cilostazol resulted in a significant decrease in total cholesterol (WMD ?8.47 mg/dl, 95% CI ?14.18, ?2.75; P = 0.004) and LDL-C (WMD ?8.25 mg/dl, 95% CI ?14.15, ?2.36; P = 0.006) and favorable trends in reducing triglyceride (WMD ?15.83 mg/dl, 95% CI ?32.14, 0.48; P = 0.06).ConclusionIt suggests that cilostazol may have beneficial effects in preventing the progression of carotid atherosclerosis and improving pro-atherogenic lipid profile, especially in patients with T2DM. Whether the anti-atherosclerotic effect of cilostazol is independent of improving pro-atherogenic dyslipidemia is worth further investigation.     

Gender differences in the lipid profile of dyslipidemic subjects

ObjectiveWe evaluated the gender-associated differences in lipid profile of subjects intended to receive lipid-lowering therapy with emphasis on the associations between triglycerides (TG) and other plasma lipid variables.DesignLipid profiles of 1385 patients [aged 55 ± 11 years, 549 women (40%)] were evaluated. Eligible subjects fulfilled one or more of the following criteria: total cholesterol (TC) ≥ 6.2 mmol/l, TG ≥ 1.7 mmol/l, and high-density lipoprotein cholesterol (HDL-C) < 1.0 mmol/l. Patients were divided into subgroups according to TG and HDL-C levels.ResultsWomen aged on average 3.5 years older, had higher TC and HDL-C, lower TG and a correspondingly lower TC/HDL-C ratio than men. High TG and low HDL-C in tandem appeared twice more frequently in men. Inverse correlations between HDL-C and TG levels were found to exist in the entire cohort (r = ? 0.354, p < 0.001) and in all various subgroups. In the subgroup with TG < 1.7 mmol/l, women had higher TC and HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men. In the subgroup with TG ≥ 1.7 mmol/l, women had higher TC and HDL-C levels and lower TC/HDL ratio compared with men. In the subgroup with HDL-C ≥ 1.0 mmol/l women had higher HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men.ConclusionsElevated TG levels and low HDL-C in tandem are common lipid abnormalities in the clinical setting of primary and secondary preventions. Gender-associated differences in the lipid profile are evident in subjects presenting with dyslipidemia and might be of potential relevance for diagnostics and therapy for the prevention of atherosclerosis.     

Low serum testosterone in men is inversely associated with non-fasting serum triglycerides: the Tromsø study

ObjectiveTo study the relationships between endogenous testosterone, sex hormone-binding globulin (SHBG) and serum lipids in non-fasting men.MethodsWe performed a cross-sectional study in 1274 men without known cardiovascular disease who participated in a population-based study, the 1994/1995 Tromsø study. Anthropometric characteristics were measured and questionnaires regarding lifestyle and medical history were completed. Non-fasting blood samples were drawn between 08.00 and 16.00 h, and total testosterone, SHBG, triglycerides (TG), total cholesterol (TC) and high-density lipoprotein (HDL) were analyzed.ResultsIn stratified analyses based on sampling time, a linear increase in serum TG levels was found in men with total testosterone levels below the 50th percentile during the day (p for trend = 0.004). In contrast, serum triglycerides did not change during the day in men with testosterone levels above the 50th percentile. In regression analyses, total testosterone and SHBG were inversely and independently associated with TG (p < 0.001 and p < 0.001 respectively), and positively and independently associated with HDL (p = 0.005 and p < 0.001, respectively). Men with an unfavorable lipid profile (HDL <0.90 and TG >1.8) had significantly lower levels of total testosterone and SHBG (p = 0.004 and p < 0.001, respectively) in age and BMI adjusted analyses, compared to men with a normal lipid profile.ConclusionsLow serum total testosterone was associated with a linear increase in serum TG during the day, and was independently associated with an unfavorable lipid profile. Our findings may indicate that low total testosterone is associated with impaired TG metabolism in men.     

Blood lipid levels in relation to glucose status in European men and women without a prior history of diabetes: The DECODE Study

ObjectiveDyslipidaemia is present not only in diabetic but also in prediabetic subjects. The purpose of this study is to investigate the relationship between lipid and glucose levels in a large European population without a prior history of diabetes.Research design and methodsData from the population-based studies of 8960 men and 10,516 women aged 35–74 years representing 15 cohorts in 8 European countries were jointly analyzed. Multivariate adjusted linear regression analyses with standardized coefficients (β) were performed to estimate the relationship between lipid and plasma glucose.ResultsIn subjects without a prior history of diabetes, positive relationships were shown between fasting plasma glucose (FPG) and total cholesterol (TC) (β = 0.06 and 0.03, respectively for men and women, p < 0.01), triglycerides (TG) (β = 0.14 and 0.12, p < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C) (β = 0.06 and 0.03, p < 0.01) and TC to HDL ratio (β = 0.06 and 0.05, p < 0.001) but a negative trend between FPG and HDL-C (β = −0.02, p > 0.05 in men and β = −0.03, p < 0.05 in women). The relationship between lipid and 2-h plasma glucose (2hPG) followed a similar pattern as that for FPG, except that TC was not increased and HDL-C was reduced in both sexes in subjects with impaired glucose tolerance (IGT).ConclusionsFor cardiovascular prevention, the different lipid patterns between impaired fasting glucose (IFG) and IGT may deserve further attention to evaluate the combined risks of dyslipidaemia and elevated glucose levels below the diagnostic threshold of diabetes.     

Non-HDL cholesterol is strongly associated with coronary artery calcification in asymptomatic individuals

BackgroundGrowing evidence shows that non-high-density lipoprotein cholesterol (Non-HDL-C) is a strong and independent predictor of cardiovascular disease (CVD). Few studies have assessed the association between traditional lipid measures and subclinical end points. In this study we analyzed the association of Non-HDL-C, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) with coronary artery calcium (CAC), a marker of subclinical atherosclerosis.MethodsThe study population consisted of 1611 consecutive asymptomatic individuals (67% men, mean age: 53 ± 10 years) referred to a single electron beam tomography (EBT) facility for CAC screening. Multivariate logistic regression was used to test the association between increasing quartiles of lipid levels and presence of CAC score (CACS) > 0 and CACS ≥ 100, with the lowest levels (first quartile) of lipid values as reference.ResultsOverall CACS of 0, 1–99, 100–399 and ≥400, were observed in 35%, 44%, 12% and 9% of the study subjects, respectively. The prevalence of CAC increased significantly across increasing quartiles of LDL-C, TG and Non-HDL-C (all p < 0.0001), whereas CACS was significantly lower across increasing quartiles of HDL-C (p < 0.001). In a multivariate model controlling for age, gender, race, cigarette smoking, hypertension, family history of coronary artery disease and obesity, there was a significant increase in the prevalence of CAC with increasing values of each lipid variable. In a multivariate model simultaneously controlling for increasing quartiles of the remaining lipid variables, only the association of Non-HDL-C with CACS > 0 remained statistically significant (p = 0.002). Similar results were observed with CACS ≥ 100 (p = 0.038).ConclusionIn this study Non-HDL-C was more strongly associated with subclinical atherosclerosis than all other conventional lipid values. These data suggests that Non-HDL-C may be an important treatment target in primary prevention.     

Apolipoprotein E polymorphism is associated with both carotid and coronary atherosclerosis in patients with coronary artery disease

Background and aimsApolipoprotein E (apoE) polymorphism plays a significant role in the development of atherosclerosis and cardiovascular disease. Therefore, the aim of the present study was to examine the association between apoE polymorphism and carotid intima-media thickness (IMT), and severity and extent of coronary artery disease (CAD).Methods and resultsB-mode ultrasound and quantitative coronary angiography (QCA) were used to assess carotid, and coronary artery atherosclerosis in 91 patients with clinically suspected CAD referred for cardiac catheterization. Two apoE phenotype groups were defined: apoE3 (E3/E3) and apoE4 (including E4/E3, E4/E4 phenotypes). Maximum IMT was higher in the apoE4 group than in the apoE3 group (p = 0.022). The global atheroma burden index was similarly higher in the apoE4 group than in the apoE3 group (p = 0.033). ApoE4 subjects had higher levels of apolipoprotein B (apoB) (p = 0.008), triglycerides (p = 0.006), remnant lipoprotein-cholesterol (RLP-C) (p = 0.023), and lipoprotein(a) [(Lp(a)] (p = 0.041) than apoE3 subjects. The mean LDL particle size was smaller in the apoE4 group than in the apoE3 group (p = 0.041).ConclusionsApoE polymorphism was associated with both carotid and coronary atherosclerosis. Patients with the apoE4 isoform had an increased carotid IMT and a more severe and extensive CAD than patients with the apoE3 isoform.     

Use of ezetimibe results in more patients reaching lipid targets without side effects

BackgroundEzetimibe's mechanism of action, complementary to that of statins, makes it a useful therapeutic option in patients intolerant of lipid-lowering drugs or in those not achieving target lipid levels.ObjectivesTo evaluate the efficacy and safety of ezetimibe in a longterm follow-up of lipid clinic patients with emphasis on motivation for use and the impact on achievement of target lipid levels.MethodsTwo hundred and ninety-five clinic patients who were prescribed and took ezetimibe in the 13-month period following the drug's availability in Canada were identified from our database. Patients’ history and laboratory data were collected before and at first visit after the ezetimibe therapy was started. Paired t-test and chi-square test were used for statistical comparisons of ezetimibe's effect on lipid parameters and the achievement of target lipid-levels respectively.ResultsEzetimibe treatment increased significantly the proportion of patients achieving lipid targets (by 25% for LDL-C and by 21.7% for TC/HDL-C) significantly by 18% (p < 0.001) and TC/HDL-C by 15% (p < 0.011). The effect of ezetimibe in combination with other lipid-lowering therapies was similar; LDL-C decreased by 22% (p < 0.001) and TC/HDL-C by 15.4% (p < 0.011). The same lipid-lowering effect was seen in patients with diabetes. In this subgroup, addition of ezetimibe to ongoing therapy led to three- and two-fold increase in LDL-C and TC/HDL-C target levels achievement, respectively. Only 7% of patients discontinued ezetimibe treatment due to side effects.ConclusionIn patients referred to the lipid clinic (typically because of side effects or failure to reach targets on other lipid-lowering therapy) treatment with ezetimibe significantly increased proportion of those achieving their target lipid levels. This was not accompanied by significant side effects.     

ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance

ObjectiveLow plasma high-density lipoprotein cholesterol (HDL-C) concentration is associated with the metabolic syndrome (MetS) and increased prevalence of cardiovascular disease (CVD). Animal and human studies report infusion of apolipoprotein A-1 (apoA-1) can reduce endothelial dysfunction, and/or induce regression of atherosclerosis. However, the direct mechanisms underlying the vascular benefits of either apoA-1 or HDL-C remain unclear. In this study, we assessed the ability of reconstituted HDL (rHDL) to improve vascular complications of MetS, including left ventricular (LV)-hypertrophy, arterial cholesterol deposition and myocardial lesion development.Methods and resultsObese insulin resistant (IR) JCR:LA-cp rats were infused with rHDL (0.4 mg/kg) over 3 days before assessing cardiac function (Echocardiography) at days 7 and 50 post-infusion, as well as haematoxylin and eosin staining of myocardial lesions at day 50. Acute ex vivo arterial cholesterol deposition was assessed with acute infusion of rHDL ex-vivo. Infusion of rHDL partially corrected abnormal diastolic compliance (18%; *p < 0.05) and improved parameters of cardiac function in IR rats. Further, acute rHDL infusion in carotid vessels reduced remnant lipoprotein associated-cholesterol deposition (30–86%; **p < 0.01) ex vivo in IR and male Wistar rats and reduced (41%; *p < 0.05) the frequency of early-stage myocardial lesions in IR rats.ConclusionShort-term infusion of rHDL may beneficially reduce chronic vascular sequelae of MetS, including temporary improvement in LV-dysfunction, acute reduction of acute arterial cholesterol deposition and the development of early-stage myocardial lesions in the JCR:LA-cp rat.     

Correlation of cardiorespiratory fitness with risk factors for cardiovascular disease in children with type 1 diabetes mellitus

The objective of this study was to correlate CRF with cardiovascular risk factors in T1DM children.MethodsFifty children and adolescents aged between 9 and 17 years with no diabetes complications and a mean diabetes duration of 4.6 years were selected. Antropometric, sexual maturation and blood pressure data were evaluated. CRF level was assessed with a 20-m shuttle run test. Laboratory tests were performed to verify fasting lipids and glycated hemoglobin. Statistical analyses were made with Pearson partial correlation, t test, and one-way ANOVA, with p ≤ 0.05.ResultsAfter adjustment for body adiposity and sexual maturity, inverse correlations among CRF and TC, TG, TC/HDL-C, TG/HDL-C, non-HDL-C, and SBP were statistically significant. Variables differing by sex included weight Z score, BMI Z score, skinfold thickness, percentage of body fat, and DBP. Boys had higher CRF compared to girls. CRF and TC differed significantly by sexual maturation status.ConclusionAn inverse and significant relationship between CRF and most lipid profile's components and SBP in poor controlled T1DM children and adolescents was found, independently of body adiposity.     

Non-high-density lipoprotein cholesterol is a practical predictor of long-term cardiac death after coronary artery bypass grafting

BackgroundRecent studies have demonstrated that non-high-density lipoprotein cholesterol (non-HDL-C) can predict the risk of cardiovascular events among general population without coronary heart disease (CHD). However, few studies have investigated the predictive value of non-HDL-C for long-term prognosis in patients with CHD. The purpose of this study was to investigate whether non-HDL-C can predict long-term cardiovascular events in patients with CHD who underwent coronary artery bypass grafting (CABG).MethodsWe enrolled 1074 consecutive patients who underwent CABG at Juntendo University Hospital between 1984 and 1994, and obtained mortality data through 2000. We divided the patients into 2 groups by the median non-HDL-C level at baseline (180 mg/dL) and used Kaplan–Meier method with log-rank test for survival analyses. Cox proportional-hazard regression model was used to calculate the relative risk (RR) of cardiac death.ResultsThe mean follow-up period was 10.6 ± 3.5 years. The survival rate of cardiac death was significantly lower in the high non-HDL-C group than that in the low non-HDL-C group (log-rank test; p = 0.006). Furthermore, in proportional regression analysis adjusted for conventional coronary risk factors, metabolic syndrome, statin treatment, and use of artery bypass graft, the increased levels of non-HDL-C were significant and independent predictor of cardiac death beyond other lipid parameters (RR1.22; by 10 mg/dL non-HDL-C increasing, 95% confidence interval 1.03–1.44; p < 0.05).ConclusionsThe increased levels of non-HDL-C were significantly associated with an increased risk of cardiac death. Baseline non-HDL-C levels may be a practical predictor of long-term cardiac death in patients with CHD after CABG.     

Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis

BackgroundTo evaluate the impact of familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) on arterial properties and the effects of statins.MethodsWe meta-analyzed 51 studies providing data for 4,057 FH patients and 732 FCH patients with random-effects models, meta-regression analysis and publication bias analysis. The main outcomes of interest were (1) brachial artery flow-mediated dilation (FMD), (2) intima-media thickness (IMT), and (3) change of IMT and FMD after treatment with statins.ResultsCompared to normolipidemic controls, FH patients had lower FMD [pooled mean difference (MD): ?5.31%, 95% CI ?7.09 to ?3.53%, P < 0.001] and higher carotid IMT (pooled MD: 0.12 mm, 95% CI 0.09–0.15 mm, P < 0.001) and femoral IMT (pooled MD: 0.35 mm, 95% CI 0.18–0.51 mm, P < 0.001). FCH patients had lower FMD and increased IMT (pooled MD: ?3.60%, 95% CI ?6.69 to ?0.50%, P = 0.023; and 0.06 mm, 95% CI 0.04–0.08 mm, P < 0.001, respectively). Total and LDL-cholesterol was a significant determinant of FMD and carotid IMT in FCH patients and of FMD and femoral IMT in FH patients. In FH patients, statins improved FMD (pooled MD of change: 5.39%, 95% CI 2.86–7.92%, P < 0.001) and decreased carotid IMT (pooled MD of change: ?0.025 mm, 95% CI ?0.042 to ?0.009 mm, P = 0.003). Changes of both FMD and IMT with statins correlated with the duration × treatment intensity product in FH patients (both P < 0.01). Additionally, statins improved FMD in FCH patients (pooled MD of change: 2.06%, 95% CI 0.43–3.69%, P = 0.013). No significant publication bias was detected.ConclusionArterial properties are impaired in subjects with FH or FCH. Statins improve arterial function and structure in FH patients in a treatment intensity-related manner.