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Meta-analysis of the Relation of Body Mass Index to Cardiovascular Outcomes in Patients Receiving Intensive Low-Density Lipoprotein Cholesterol Lowering Therapy.

ABSTRACT: The impact of body mass index (BMI) on cardiovascular outcomes in patients receiving intensive low-density lipoprotein cholesterol (LDL-C) lowering therapy is uncertain. We performed meta-analysis of 29 randomized controlled trials using PubMed, Embase, and CENTRAL through April 2019. Therapies were grouped as more intensive LDL-C lowering therapy (statins, ezetimibe?+?statin or PCSK9 inhibitors) and less intensive LDL-C lowering therapy (less potent active control or placebo). Random effects meta-regressions and meta-analyses were performed to evaluate association of BMI with cardiovascular endpoints. In 265,766 patients, for every 1 kg/m² increase in BMI, more intensive therapy compared with less intensive therapy was associated with hazard ratio (HR) of 1.07 for cardiovascular mortality (95% confidence interval 1.02 to 1.13); HR of 1.03 for all-cause mortality (0.99 to 1.06) HR of 1.06 for myocardial infarction (1.02 to 1.09), HR of 1.08 (1.03 to 1.12) for revascularization and HR of 1.04 for MACE (1.01 to 1.07). Meta-analysis showed that patients with BMI <25 kg/m² had the highest risk reduction in mortality and cardiovascular outcomes compared with patients with BMI ?30 kg/m² (p-interaction ?0.05). In conclusion, patients with normal BMI treated with intensive LDL-C lowering regimens may derive a larger clinical benefit compared with patients with larger BMI. The results could be due to the higher mortality rate of obese patients that may artificially lower the efficacy of therapy, or due to a true therapeutic limitation in these patients.

SUBMITTER: Khan SU

PROVIDER: S-EPMC7397555 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Meta-analysis of the Relation of Body Mass Index to Cardiovascular Outcomes in Patients Receiving Intensive Low-Density Lipoprotein Cholesterol Lowering Therapy.

Khan Safi U SU Khan Muhammad U MU Riaz Haris H Raggi Paolo P Valavoor Shahul S Khan Muhammad Zia MZ Kołodziejczak Michalina M Khan Muhammad Shahzeb MS Krupica Troy T Alkhouli Mohamad M Navarese Eliano P EP

The American journal of cardiology 20191210 5

The impact of body mass index (BMI) on cardiovascular outcomes in patients receiving intensive low-density lipoprotein cholesterol (LDL-C) lowering therapy is uncertain. We performed meta-analysis of 29 randomized controlled trials using PubMed, Embase, and CENTRAL through April 2019. Therapies were grouped as more intensive LDL-C lowering therapy (statins, ezetimibe + statin or PCSK9 inhibitors) and less intensive LDL-C lowering therapy (less potent active control or placebo). Random effects me ...[more]

PMID: 31898964

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Project description:Purpose of reviewThe primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on optimizing cardiovascular health and appropriate pharmacotherapy, a mainstay of which is low-density lipoprotein-cholesterol (LDL-C) lowering. Typically, statin therapy remains the first line approach. Advances in technology and understanding of lipid metabolism have facilitated the development of several novel therapeutic targets and medications within the last decade. This review focuses on medications recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of LDL-C and ASCVD risk, as well as new therapies in the pipeline.Recent findingsNovel lipid therapies aim to lower risk of ASCVD by targeting reduction of atherogenic compounds, such as LDL, lipoprotein(a) (Lp(a)), and triglyceride-rich lipoproteins. Evolocumab and alirocumab, monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors which lower LDL-C by approximately 60%, have emerged as important therapies for use in patients with ASCVD as well as familial hypercholesterolemia (FH). Bempedoic acid, an ATP citrate lyase inhibitor, is an oral medication recently approved that can lower LDL-C by approximately 18% alone and 38% when combined with ezetimibe. Inclisiran, a small-interfering RNA (siRNA) molecule which inhibits the translation of PCSK9, is the most recently FDA-approved LDL-C lowering medication, and can reduce LDL-C by approximately 50% with twice yearly subcutaneous dosing. The cardiovascular outcome trials for bempedoic acid and inclisiran are still on-going. Evinacumab, a monoclonal antibody which targets angiopoietin-like protein 3 (ANGPTL3), has been approved for use in patients with homozygous FH. SiRNAs and anti-sense oligonucleotides (ASO) facilitating selective inhibition of the production of targeted proteins including Lp(a) and ANGLPTL3 are active areas of clinical investigation.SummaryRecently several novel LDL-C lowering medications have been approved. New therapeutic targets have been identified and present additional means of lowering LDL-C and other atherogenic compounds for patients who remain at high ASCVD risk.

Project description:AimsLipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events.Methods and resultsCardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio Ptrend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median -5.0 [-13.6, 0] mg/dL) and corrected LDL-C (median -51.3 [-67.1, -34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events.ConclusionBaseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.

Project description:Background Conventional "low-density lipoprotein cholesterol (LDL-C)" assays measure cholesterol content in both low-density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of "LDL-C" and corrected LDL-C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline-recommended LDL-C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from "LDL-C" to obtain corrected LDL-C values (LDL-Ccorr30). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual-patient-data meta-analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow-up). When comparing top versus bottom quartiles, the multivariable-adjusted hazard ratio for cardiovascular disease was significant for "LDL-C" (1.17; 95% CI, 1.05-1.31; P=0.005) but not for LDL-Ccorr30 (1.07; 95% CI, 0.93-1.22; P=0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline-recommended LDL-C categories when using LDL-Ccorr30 was assessed. In "LDL-C" categories of 70 to <100, 100 to <130, 130 to <190, and ≥190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL-C categories when LDL-Ccorr30 was used: 30.2% (30.0%-30.4%), 35.1% (34.9%-35.4%), 32.9% (32.6%-33.1%), and 41.1% (40.0%-42.2%), respectively. Conclusions "LDL-C" was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL-C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.

Dataset Information

Meta-analysis of the Relation of Body Mass Index to Cardiovascular Outcomes in Patients Receiving Intensive Low-Density Lipoprotein Cholesterol Lowering Therapy.

Publications

Meta-analysis of the Relation of Body Mass Index to Cardiovascular Outcomes in Patients Receiving Intensive Low-Density Lipoprotein Cholesterol Lowering Therapy.

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