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Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy.

ABSTRACT: Lipoprotein(a) [Lp(a)] has enhanced atherothrombotic properties. The ability of Lp(a) levels to predict adverse cardiovascular outcomes in patients undergoing coronary angiography has not been examined. The relationship between serum Lp(a) levels and both the extent of angiographic disease and 3-year incidence of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, and coronary revascularization) was investigated in 2,769 patients who underwent coronary angiography [median Lp(a) 16.4 mg/dl, elevated levels (?30 mg/dl) in 38%]. An elevated Lp(a) was associated with a 2.3-fold [95% confidence interval (CI), 1.7-3.2, P < 0.001] greater likelihood of having a significant angiographic stenosis and 1.5-fold (95 CI, 1.3-1.7, P < 0.001) greater chance of three-vessel disease. Lp(a)?30 mg/dl was associated with a greater rate of MACE (41.8 vs. 35.8%, P = 0.005), primarily due to a greater need for coronary revascularization (30.9 vs. 26.0%, P = 0.02). A relationship between Lp(a) levels and cardiovascular outcome was observed in patients with an LDL cholesterol (LDL-C) ?70-100 mg/dl (P = 0.049) and >100 mg/dl (P = 0.02), but not <70 mg/dl (P = 0.77). Polymorphisms of Lp(a) were also associated with both plasma Lp(a) levels and coronary stenosis, but not a greater rate of MACE. Lp(a) levels correlate with the extent of obstructive disease and predict the need for coronary revascularization in subjects with suboptimal LDL-C control. This supports the need to intensify lipid management in patients with elevated Lp(a) levels.

SUBMITTER: Nicholls SJ

PROVIDER: S-EPMC2936758 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy.

Nicholls Stephen J SJ Tang W H Wilson WH Scoffone Heather H Brennan Danielle M DM Hartiala Jaana J Allayee Hooman H Hazen Stanley L SL

Journal of lipid research 20100702 10

Lipoprotein(a) [Lp(a)] has enhanced atherothrombotic properties. The ability of Lp(a) levels to predict adverse cardiovascular outcomes in patients undergoing coronary angiography has not been examined. The relationship between serum Lp(a) levels and both the extent of angiographic disease and 3-year incidence of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, and coronary revascularization) was investigated in 2,769 patients who underwent coronary angiography [m ...[more]

PMID: 20601648

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Project description:ImportancePatients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemia and low high-density lipoprotein cholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk.ObjectiveTo determine whether fenofibrate reduces CVD risk in statin-treated patients with type 2 diabetes.Design, setting, and participantsPosttrial follow-up of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study between July 2009 and October 2014; 5 years of follow-up were completed for a total of 9.7 years at general community and academic outpatient research clinics in the United States and Canada. Of the original 5518 ACCORD Lipid Trial participants, 4644 surviving participants were selected based on the presence of type 2 diabetes and either prevalent CVD or CVD risk factors and high-density lipoprotein levels less than 50 mg/dL (<55 mg/dL for women and African American individuals).InterventionsPassive follow-up of study participants previously treated with fenofibrate or masked placebo.Main outcomes and measuresOccurrence of cardiovascular outcomes including primary composite outcome of fatal and nonfatal myocardial infarction and stroke in all participants and in prespecified subgroups.ResultsThe 4644 follow-on study participants were broadly representative of the original ACCORD study population and included significant numbers of women (n = 1445; 31%), nonwhite individuals (n = 1094; 21%), and those with preexisting cardiovascular events (n = 1620; 35%). Only 4.3% of study participants continued treatment with fenofibrate following completion of ACCORD. High-density lipoprotein and triglyceride values rapidly equalized among participants originally randomized to fenofibrate or placebo. Over a median total postrandomization follow-up of 9.7 years, the hazard ratio (HR) for the primary study outcome among participants originally randomized to fenofibrate vs placebo (HR, 0.93; 95% CI, 0.83-1.05; P = .25) was comparable with that originally observed in ACCORD (HR, 0.92; 95% CI, 0.79-1,08; P = .32). Despite these overall neutral results, we continued to find evidence that fenofibrate therapy effectively reduced CVD in study participants with dyslipidemia, defined as triglyceride levels greater than 204 mg/dL and high-density lipoprotein cholesterol levels less than 34 mg/dL (HR, 0.73; 95% CI, 0.56-0.95).Conclusions and relevanceExtended follow-up of ACCORD-lipid trial participants confirms the original neutral effect of fenofibrate in the overall study cohort. The continued observation of heterogeneity of treatment response by baseline lipids suggests that fenofibrate therapy may reduce CVD in patients with diabetes with hypertriglyceridemia and low high-density lipoprotein cholesterol. A definitive trial of fibrate therapy in this patient population is needed to confirm these findings.Trial registrationclinicaltrials.gov Identifier: NCT00000620.

Project description:BackgroundAtherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from computed tomography. HMG-CoA-reductase inhibitors (statins) are the primary pharmacotherapy used to reduce cardiovascular events, yet there is growing data that support statin use may increase coronary calcification. We set out to determine the likelihood of severe CACS in the context of chronic statin therapy.MethodsWe established a retrospective, case-control study of 1,181 U.S. veterans without coronary artery disease (CAD) from a single site, the Providence VA Medical Center. Duration of statin therapy for primary prevention was divided into 5-year categorical increments. The primary outcome was CACS derived from low-dose lung cancer screening computed tomography (LCSCT), stratified by CACs severity (none = 0; mild = 1-99; moderate = 100-399; and severe ≥400 AU). Statin duration of zero served as the referent control. Ordinal logistic regression analysis determined the association between duration of statin use and CACS categories. Proportional odds assumption was tested using likelihood ratio test. Atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index, and CKD (glomerular filtration rate of <60 ml/min/1.73 m2) were included in the adjustment models.ResultsThe mean age of the study population was 64.7±7.2 years, and 706 (60%) patients were prescribed a statin at baseline. Duration of statin therapy was associated with greater odds of having increased CACS (>0-5 years, OR: 1.71 [CI: 1.34-2.18], p<0.001; >5-10 years, OR: 2.80 [CI: 2.01-3.90], p<0.001; >10 years, OR: 5.30 [CI: 3.23-8.70], p<0.001), and the relationship between statin duration and CACS remained significant after multivariate adjustment (>0-5 years, OR: 1.49 [CI: 1.16-1.92], p = 0.002; >5-10 years, OR: 2.38 [CI: 1.7-3.35], p<0.001; >10 years, OR: 4.48 [CI: 2.7-7.43], p<0.001).ConclusionsLong-term use of statins is associated with increased likelihood of severe CACS in patients with significant smoking history. The use of CACS to interpret cardiovascular event risk may require adjustment in the context of chronic statin therapy.

Project description:BackgroundAmong patients treated with statin therapy to guideline-recommended cholesterol levels, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is at least as strong a predictor of future cardiovascular events as is residual risk assessed by low-density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients with higher LDLC levels is uncertain but has implications for the choice of preventive therapies, including bempedoic acid, an agent that reduces both LDLC and hsCRP.MethodsThe multinational CLEAR-Outcomes trial (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen Outcomes Trial) randomly allocated 13 970 statin-intolerant patients to 180 mg of oral bempedoic acid daily or matching placebo and followed them for a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and for all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse events after adjustment for traditional risk factors and randomized treatment assignment.ResultsCompared with placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months. Baseline hsCRP was significantly associated with the primary composite end point of major cardiovascular events (highest versus lowest hsCRP quartile; hazard ratio [HR], 1.43 [95% CI, 1.24-1.65]), cardiovascular mortality (HR, 2.00 [95% CI, 1.53-2.61]), and all-cause mortality (HR, 2.21 [95% CI, 1.79-2.73]). By contrast, the relationship of baseline LDLC quartile (highest versus lowest) to future events was smaller in magnitude for the primary composite cardiovascular end point (HR, 1.19 [95% CI, 1.04-1.37]) and neutral for cardiovascular mortality (HR, 0.90 [95% CI, 0.70-1.17]) and all-cause mortality (HR, 0.95 [95% CI, 0.78-1.16]). Risks were high for those with elevated hsCRP irrespective of LDLC level. Bempedoic acid demonstrated similar efficacy in reducing cardiovascular events across all levels of hsCRP and LDLC.ConclusionsAmong contemporary statin-intolerant patients, inflammation assessed by hsCRP predicted risk for future cardiovascular events and death more strongly than hyperlipidemia assessed by LDLC. Compared with placebo, bempedoic acid had similar efficacy for reducing cardiovascular risk across hsCRP and LDLC strata.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02993406.

Project description:PurposeDyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition.MethodsThis observational study included 40 volunteers (50% men, aged 32-65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days.ResultsThe largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, - 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (- 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, - 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (- 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (- 0.16 ± 0.05 mmol/L), LDL2-C (- 0.30 ± 0.06 mmol/L) and LDL3-C (- 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (- 5.18 ± 1.26 nmol/L), as well as large (- 244.13 ± 39.45 nmol/L) and small LDL particles (- 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (- 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged.ConclusionOur results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia.Trial registrationStudy registration number: DRKS-ID: DRKS00010111 Date of registration: 03/06/2016 "retrospectively registered".

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Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy.

Publications

Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy.

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