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The challenge of multiple cardiovascular risk factor control outside Western Europe: Findings from the International ChoLesterol management Practice Study.
Blom, DJ, Santos, RD, Daclin, V, Mercier, F, Ruiz, AJ, Danchin, N, ,
European journal of preventive cardiology. 2020;(13):1403-1411
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Abstract
BACKGROUND Comprehensive control of multiple cardiovascular risk factors reduces cardiovascular risk but is difficult to achieve. DESIGN A multinational, cross-sectional, observational study. METHODS The International ChoLesterol management Practice Study (ICLPS) investigated achievement of European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline low-density lipoprotein cholesterol (LDL-C) targets in patients receiving lipid-modifying therapy in countries outside Western Europe. We examined the rate of, and association between, control of multiple risk factors in ICLPS participants with dyslipidaemia, diabetes and hypertension (N = 2377). RESULTS Mean (standard deviation) age of patients was 61.4 (10.4) years; 51.3% were male. Type 2 diabetes was the most common form of diabetes (prevalence, 96.9%). The prevalence of metabolic syndrome was 67.8%, obesity 40.4%, atherosclerotic disease 39.6% and coronary artery disease 33.5%. All patients were at high (38.2%) or very high (61.8%) cardiovascular risk according to ESC/EAS guidelines. Body mass index (BMI) was <25 kg/m2 in 20.3% of patients, 62.8% had never smoked and 25.2% were former smokers. Overall, 12.2% achieved simultaneous control of LDL-C, diabetes and blood pressure. Risk factor control was similar across all participating countries. The proportion of patients achieving individual guideline-specified treatment targets was 43.9% for LDL-C, 55.5% for blood pressure and 39.3% for diabetes. Multiple correspondence analysis indicated that control of LDL-C, control of blood pressure, control of diabetes, BMI and smoking were associated. CONCLUSION Comprehensive control of multiple cardiovascular risk factors in high-risk patients is suboptimal worldwide. Failure to control one risk factor is associated with poor control of other risk factors.
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Genetic Variants Associated With Plasma Lipids Are Associated With the Lipid Response to Niacin.
Tuteja, S, Qu, L, Vujkovic, M, Dunbar, RL, Chen, J, DerOhannessian, S, Rader, DJ
Journal of the American Heart Association. 2018;(19):e03488
Abstract
Background Niacin is a broad-spectrum lipid-modulating drug, but its mechanism of action is unclear. Genome-wide association studies have identified multiple loci associated with blood lipid levels and lipoprotein (a). It is unknown whether these loci modulate response to niacin. Methods and Results Using data from the AIM - HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL /High Triglycerides and Impact on Global Health Outcomes) trial (n=2054 genotyped participants), we determined whether genetic variations at validated loci were associated with a differential change in plasma lipids and lipoprotein (a) 1 year after randomization to either statin+placebo or statin+niacin in a variant-treatment interaction model. Nominally significant interactions ( P<0.05) were found for genetic variants in MVK , LIPC , PABPC 4, AMPD 3 with change in high-density lipoprotein cholesterol; SPTLC 3 with change in low-density lipoprotein cholesterol; TOM 1 with change in total cholesterol; PDXDC 1 and CYP 26A1 with change in triglycerides; and none for lipoprotein (a). We also investigated whether these loci were associated with cardiovascular events. The risk of coronary disease related death was higher in the minor allele carriers at the LIPC locus in the placebo group (odds ratio 2.08, 95% confidence interval 1.11-3.90, P=0.02) but not observed in the niacin group (odds ratio 0.89, 95% confidence interval 0.48-1.65, P=0.7); P-interaction =0.02. There was a greater risk for acute coronary syndrome (odds ratio 1.85, 95% confidence interval 1.16-2.77, P=0.02) and revascularization events (odds ratio 1.64, 95% confidence interval 1.2-2.22, P=0.002) in major allele carriers at the CYP 26A1 locus in the placebo group not seen in the niacin group. Conclusions Genetic variation at loci previously associated with steady-state lipid levels displays evidence for lipid response to niacin treatment. Clinical Trials Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00120289.
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High HDL cholesterol level after treatment with pitavastatin is an important factor for regression in carotid intima-media thickness.
Okumura, K, Tsukamoto, H, Tsuboi, H, Hirayama, H, Kamiya, H, Watarai, M, Ishiki, R, Murohara, T, ,
Heart and vessels. 2015;(2):154-61
Abstract
This study is a prospective multicenter study designed to investigate the effects of lipid-lowering therapy with pitavastatin on atherosclerotic plaque in patients with coronary heart disease, and to determine which factor is more closely associated with plaque regression. Participants (n = 63) were treated with pitavastatin for 12 months, and the carotid intima-media thickness (IMT) was measured by ultrasound before and after treatment. Mean IMT slightly but significantly decreased (from 0.99 ± 0.33 to 0.94 ± 0.28 mm for overall, P = 0.01) regardless of the presence of pretreatment with other statins. There were no significant relations with hs-CRP, malondialdehyde-LDL, LDL cholesterol, and smaller LDL cholesterol levels despite their decrease by pitavastatin. Decreases in mean IMT were observed significantly more frequently in subjects with high on-treatment HDL cholesterol levels than with low HDL cholesterol levels (P = 0.017). The change in mean IMT tended to be inversely correlated with increments in HDL cholesterol and apolipoprotein A-I. The IMT regression was more often observed in the absence of diabetes and metabolic syndrome. In conclusion, we demonstrated that treatment with pitavastatin attenuated atherosclerotic plaque. This effect was associated with the level of HDL cholesterol, and was stronger in the absence of diabetes and metabolic syndrome in our ischemic heart disease patients.
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Response to statin therapy in obstructive sleep apnea syndrome: a multicenter randomized controlled trial.
Joyeux-Faure, M, Tamisier, R, Baguet, JP, Dias-Domingos, S, Perrig, S, Leftheriotis, G, Janssens, JP, Trzepizur, W, Launois, SH, Stanke-Labesque, F, et al
Mediators of inflammation. 2014;:423120
Abstract
RATIONALE Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. METHODS This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. RESULTS 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m(2). In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (-0.29; 0.28), P = 0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: -6.34 mmHg (-12.68; -0.01), P = 0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. CONCLUSION In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.
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[Dyslipemia in diabetics treated with statins. Results of the DYSIS study in Spian].
Millán, J, Alegría, E, Guijarro, C, Lozano, JV, Vitale, GC, González-Timón, B, González-Juanatey, JR
Medicina clinica. 2013;(10):430-6
Abstract
BACKGROUND AND OBJECTIVE Type 2 diabetes mellitus (DM2) is characterized by carrying a high cardiovascular risk. This situation underscores the importance of intensively treating the risk factors present in diabetic patients, notably dyslipemia. The treatment with cholesterol-lowering drugs may be especially effective to reduce the cardiovascular risk in diabetic patients. Therefore, LDL-cholesterol is a priority target in the lipid management of these patients. This study analyzes the alterations in the lipid profile of diabetic patients receiving treatment with statins, which therefore may contribute to persistent cardiovascular risk in such individuals. PATIENTS AND METHODS The DYSIS (Dyslipidemia International Study) is an international, observational trial analyzing the lipid profile of patients treated with statins and followed-up on in outpatient clinics by primary care physicians and specialists. This study is referred to the data on the diabetic patients. RESULTS Of the total patients enrolled in the DYSIS, the present study included 3703 patients, 39% being diabetics. A total of 59.2% of diabetics showed LDL-C out of goal; triglyceride elevation was observed in 43.6% and 36.4% showed low HDL-C. In diabetics patients with coronary heart disease, 31% had uncontrolled levels of all three lipid parameters. The prevalence of out of goal LDL-C in diabetic patients with metabolic syndrome was close to 60%; 39.8% had low levels of HDL-C and 46,6% high levels of triglycerides. In addition, 57% of diabetic patients with obesity showed LDL-C out of control, despite statins treatment. CONCLUSIONS Cardiovascular diseases remain the main cause of morbidity-mortality in patients with DM2. The results of the present study show that in diabetic patients the degree of control is very limited with regard to LDL-cholesterol. More than half of diabetic patients treated with statins had LDL-cholesterol out of goal. The level of dyslipidemia control was low, despite statins treatment. Therefore, the detection of atherogenic dyslipidemia may point to the advisability of using combination therapy for dyslipidemia in diabetic patients.
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High-dose statin monotherapy versus low-dose statin/ezetimibe combination on fasting and postprandial lipids and endothelial function in obese patients with the metabolic syndrome: The PANACEA study.
Westerink, J, Deanfield, JE, Imholz, BP, Spiering, W, Basart, DC, Coll, B, Kastelein, JJ, Visseren, FL
Atherosclerosis. 2013;(1):118-24
Abstract
BACKGROUND Low-dose statin therapy in combination with ezetimibe, an inhibitor of intestinal cholesterol absorption, lowers plasma LDL-cholesterol levels to a similar degree as high-dose statin monotherapy. This study assessed whether similar LDL-cholesterol lowering with simvastatin/ezetimibe combination therapy improves fasting and postprandial arterial endothelial function compared to high-dose statin therapy alone. METHODS Multicenter, double-blind, crossover trial in 100 abdominally obese patients with the metabolic syndrome, randomized to 6 weeks' treatment with simvastatin 80 mg or simvastatin/ezetimibe 10/10 mg. Flow mediated dilatation (FMD) and peripheral arterial tonometry (EndoPAT) as well as plasma lipids were measured in the fasting state and after an oral lipid load at baseline and after both treatments. RESULTS Fasting LDL-cholesterol levels (3.57 mmol/L at baseline) were reduced to 1.79 mmol/L following treatment with simvastatin 80 mg and 1.81 mmol/L with simvastatin/ezetimibe 10/10 mg, respectively. Plasma lipids were similar at 4 h after an oral lipid load following both treatments for 6 weeks. Fasting endothelial function was also similar with both treatments when assessed by FMD (adjusted mean ± SE: 4.35 ± 0.19 vs. 4.43 ± 0.18; P = 0.777) and EndoPAT (2.12 ± 0.05 vs 2.20 ± 0.05; P = 0.304). After an oral fat load, changes in endothelial function were also comparable for both treatments as assessed by FMD (-0.34 ± 0.21 vs. -0.43 ± 0.20; P = 0.766) and EndoPAT (0.00 ± 0.07 vs. -0.04 ± 0.08; P = 0.712). CONCLUSION Treatment with simvastatin/ezetimibe 10/10 mg induced no difference in endothelial function in the fasting and postprandial state compared to simvastatin 80 mg while attaining similar LDL-c levels in obese patients with metabolic syndrome.
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Clustering of metabolic syndrome components attenuates coronary plaque regression during intensive statin therapy in patients with acute coronary syndrome: the JAPAN-ACS subanalysis study.
Takashima, H, Ozaki, Y, Morimoto, T, Kimura, T, Hiro, T, Miyauchi, K, Nakagawa, Y, Yamagishi, M, Daida, H, Mizuno, T, et al
Circulation journal : official journal of the Japanese Circulation Society. 2012;(12):2840-7
Abstract
BACKGROUND The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) trial showed that intensive statin therapy could induce significant coronary plaque regression in acute coronary syndrome (ACS). We evaluated the impact of metabolic syndrome (MetS) and its components on coronary plaque regression in the JAPAN-ACS patients. METHODS AND RESULTS Serial intravascular ultrasound measurements over 8-12 months were performed in 242 ACS patients receiving pitavastatin or atorvastatin. Patients were divided into groups according to the presence of MetS or the number of MetS components. Although the percent change in plaque volume (%PV) was not significantly different between the MetS (n=119) and non-MetS (n=123) groups (P=0.50), it was significantly associated with an increasing number of MetS components (component 0: -24.0%, n=7; components 1: -20.8%, n=31; components 2: -16.1%, n=69; components 3: -18.7%, n=83; components 4: -13.5%, n=52; P=0.037 for trend). The percent change in body mass index (%BMI) significantly correlated with %PV (r=0.15, P=0.021), especially in the MetS components 4 group (r=0.35, P=0.017). In addition, %BMI was an independent predictor of plaque regression after adjustment for the changes of low- and high-density lipoprotein cholesterol, triglycerides and HbA(1c). CONCLUSIONS The clustering of MetS components, but not the presence of MetS itself, could attenuate coronary plaque regression during intensive statin therapy in ACS patients. Therefore, to achieve a greater degree of plaque regression, it is necessary to treat to each MetS component and use lifestyle modification.
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The effect of rosuvastatin on incident pneumonia: results from the JUPITER trial.
Novack, V, MacFadyen, J, Malhotra, A, Almog, Y, Glynn, RJ, Ridker, PM
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2012;(7):E367-72
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Abstract
BACKGROUND Evidence from observational studies have raised the possibility that statin treatment reduces the incidence of certain bacterial infections, particularly pneumonia. We analyzed data from a randomized controlled trial of rosuvastatin to examine this hypothesis. METHODS We analyzed data from the randomized, double-blind, placebo-controlled JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). In this trial, 17,802 healthy participants (men 50 years and older and women 60 and older) with a low-density lipoprotein (LDL) cholesterol level below 130 mg/dL (3.4 mmol/L) and a high-sensitivity C-reactive protein level of 2.0 mg/L or greater were randomly assigned to receive either rosuvastatin or placebo. We evaluated the incidence of pneumonia on an intention-to-treat basis by reviewing reports of adverse events from the study investigators, who were unaware of the treatment assignments. RESULTS Among 17,802 trial participants followed for a median of 1.9 years, incident pneumonia was reported as an adverse event in 214 participants in the rosuvastatin group and 257 in the placebo group (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.69-1.00). In analyses restricted to events occurring before a cardiovascular event, pneumonia occurred in 203 participants given rosuvastatin and 250 given placebo (HR 0.81, 95% CI 0.67-0.97). Inclusion of recurrent pneumonia events did not modify this effect (HR 0.81, 95% CI 0.67-0.98), nor did adjustment for age, sex, smoking, metabolic syndrome, lipid levels and C-reactive protein level. INTERPRETATION Data from this randomized controlled trial support the hypothesis that statin treatment may modestly reduce the incidence of pneumonia. (ClinicalTrials.gov trial register no. NCT0023968.).
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Association between the changes in renal function and serum uric acid levels during multifactorial intervention and clinical outcome in patients with metabolic syndrome. A post hoc analysis of the ATTEMPT study.
Athyros, VG, Karagiannis, A, Ganotakis, ES, Paletas, K, Nicolaou, V, Bacharoudis, G, Tziomalos, K, Alexandrides, T, Liberopoulos, EN, Mikhailidis, DP, et al
Current medical research and opinion. 2011;(8):1659-68
Abstract
AIM: To assess the effects of long-term multifactorial intervention on renal function and serum uric acid (SUA) levels and their association with estimated cardiovascular disease (eCVD) risk and actual CVD events. METHODS This prospective, randomized, target-driven study included 1123 subjects (45.6% men, age 45-65 years) with metabolic syndrome (MetS) but without diabetes or CVD. Patients were randomized to multifactorial treatment. Atorvastatin was titrated from 10-80 mg/day aiming at a low density lipoprotein cholesterol (LDL-C) target of <100 mg/dl (group A) or an LDL-C target of <130 mg/dl (group B). Changes in estimated glomerular filtration rate (eGFR) and SUA levels were recorded in all patients and in the subgroup with stage 3 chronic kidney disease (CKD; eGFR = 30-59 ml/min/1.73 m(2); n = 349). We used ANOVA to compare changes within the same group, unpaired Student t-test to compare results between groups at specific time points, and log-rank test to compare event free survival. RESULTS The eCVD-risk reduction was greater in group A. In the overall study population, eGFR increased by 3.5% (p < 0.001) and SUA levels fell by 5.6% (p < 0.001). In patients from group A with stage 3 CKD (group A1; n = 172), eGFR increased by 11.1% (p < 0.001) from baseline and by 7.5% (p < 0.001) in group B1 (n = 177; p < 0.001 vs. the change in group A1). The corresponding fall in SUA levels was 10.7% in group A1 (p < 0.001 vs. baseline) and 8.3% in group B1 (p < 0.001 vs. baseline and group A1). These changes were mainly attributed to atorvastatin treatment. Among the CKD stage 3 patients there were no CVD events in group A1, while 6 events occurred in group B1 (p = 0.014). CONCLUSIONS Multifactorial intervention in patients with MetS without established CVD improved renal function and reduced SUA levels. These changes were more prominent in stage 3 CKD patients and might have contributed to the reduction in eCVD risk and clinical events. Original study registration number [ClinicalTrials.gov ID: NCT00416741].
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Eligibility for statin therapy by the JUPITER trial criteria and subsequent mortality.
Cushman, M, McClure, LA, Lakoski, SG, Jenny, NS
The American journal of cardiology. 2010;(1):77-81
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Justification for the Use of Statins in Primary Prevention: An Intervention Trial Using Rosuvastatin (JUPITER) reported reduced cardiovascular and all-cause mortality with statin treatment in patients with elevated C-reactive protein (CRP) and average cholesterol levels who were not eligible for lipid-lowering treatment on the basis of existing guidelines. The aim of this study was to determine the prevalence of eligibility and mortality in a general population sample on the basis of eligibility for statin treatment using the JUPITER criteria. The study group consisted of 30,229 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, an observational study of US African American and white participants aged > or =45 years, enrolled in their homes from 2003 to 2007 and followed biannually by telephone. Among 11,339 participants age eligible for JUPITER and without vascular diagnoses or using lipid-lowering treatment, 21% (n = 2,342) met JUPITER entry criteria. Compared with JUPITER participants, they had similar low-density lipoprotein cholesterol and CRP levels, were more often women, were more often black, had metabolic syndrome, and used aspirin for cardioprotection. Over 3.5 years of follow-up, the mortality rate in REGARDS participants eligible for JUPITER was 1.17 per 100 patient-years (95% confidence interval 0.94 to 1.42). Compared with those otherwise JUPITER eligible who had CRP levels <2 mg/L (n = 2,620), those with CRP levels > or =2 mg/L had a multivariate-adjusted relative risk of 1.5 (95% confidence interval 1.1 to 2.2) for total mortality. In conclusion, 21% not otherwise eligible would be newly eligible for lipid lowering treatment on the basis of JUPITER trial eligibility.