| Title: | Lipoprotein(a), C-Reactive Protein, and Cardiovascular Risk in Primary and Secondary Prevention Populations |
| Journal: | JAMA Cardiology |
| Published: | 1 Apr 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38353970/ |
| DOI: | https://doi.org/10.1001/jamacardio.2023.5605 |
Publication 8735
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Abstract
Importance: Elevated lipoprotein(a) (Lp[a]) is a putative causal risk factor for atherosclerotic cardiovascular disease (ASCVD). There are conflicting data as to whether Lp(a) may increase cardiovascular risk only in the presence of concomitant inflammation.</p>
Objective: To investigate whether Lp(a) is associated with cardiovascular risk independent of high-sensitivity C-reactive protein (hs-CRP) in both primary and secondary prevention populations.</p>
Design, Setting, and Participants: This cohort study uses data from 3 distinct cohorts, 1 population-based cohort and 2 randomized clinical trials. Participants included individuals from the UK Biobank (data from 2006-2010) without prevalent ASCVD, participants in the FOURIER (TIMI 59) trial (data from 2013-2017) who had baseline Lp(a) and hs-CRP data, and participants in the SAVOR-TIMI 53 trial (data from 2010-2013) who had prevalent ASCVD and baseline values for Lp(a) and hs-CRP. The data analysis took place from November 2022 to November 2023.</p>
Exposure: Baseline plasma Lp(a), considered either as a continuous variable or dichotomized at 125 nmol/L.</p>
Main Outcomes and Measures: Risk of major adverse cardiovascular events (MACE) (composite of cardiovascular death, myocardial infarction [MI], or ischemic stroke), the individual MACE components, and peripheral artery disease (PAD).</p>
Results: Among 357 220 individuals in the UK Biobank without prevalent ASCVD, 232 699 (65%) had low hs-CRP (<2 mg/L), and 124 521 (35%) had high hs-CRP (≥2 mg/L) values. In a Cox proportional hazard model adjusted for ASCVD risk factors, higher Lp(a) was associated with increased cardiovascular risk regardless of baseline hs-CRP value for MACE (hs-CRP ≥2 mg/L: hazard ratio [HR] per 50-nmol/L higher Lp[a], 1.05; 95% CI, 1.04-1.07; P < .001; for hs-CRP <2 mg/L: HR, 1.05; 95% CI, 1.04-1.07; P < .001; P = .80 for interaction), as well as MI, ischemic stroke, and PAD individually. Among 34 020 individuals in the FOURIER and SAVOR trials with baseline cardiometabolic disease, there were 17 643 (52%) with low and 16 377 (48%) with high baseline hs-CRP values. In Cox proportional hazard models using aggregated data from FOURIER and SAVOR, higher baseline Lp(a) was associated with increased cardiovascular risk regardless of baseline hs-CRP for MACE (hs-CRP ≥2 mg/L: HR per 50-nmol/L higher Lp[a], 1.02; 95% CI, 1.00-1.05; P = .04; hs-CRP <2 mg/L: HR, 1.05; 95% CI, 1.02-1.08; P < .001; P = .16 for interaction), MI, and PAD.</p>
Conclusions and Relevance: In this study, higher levels of Lp(a) were associated with MACE, MI, and PAD in both primary and secondary prevention populations regardless of baseline hs-CRP value.</p>
12 Authors
- Aeron M. Small
- Ashley Pournamdari
- Giorgio E.M. Melloni
- Benjamin M. Scirica
- Deepak L. Bhatt
- Itamar Raz
- Eugene Braunwald
- Robert P. Giugliano
- Marc S. Sabatine
- Gina M. Peloso
- Nicholas A. Marston
- Pradeep Natarajan
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