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Lipoprotein(a) and Risk of Incident Atherosclerotic Cardiovascular Disease: Impact of High-Sensitivity C-Reactive
Ron C Hoogeveen1, Margaret R Diffenderfer2,3, Elise Lim4,5
1Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Insights
Elevated lipoprotein(a) [Lp(a)] significantly increases atherosclerotic cardiovascular disease (ASCVD) risk, especially when combined with high C-reactive protein (CRP). This highlights Lp(a) as a key risk factor for cardiovascular events.
Area of Science:
- Cardiology
- Biomarkers
- Preventive Medicine
Background:
- Elevated lipoprotein(a) [Lp(a)] is a known risk factor for atherosclerotic cardiovascular disease (ASCVD).
- The 2019 ACC/AHA guidelines recommend assessing Lp(a) as an ASCVD risk-enhancing factor.
- The role of C-reactive protein (CRP) in modifying Lp(a)-associated ASCVD risk requires further investigation.
Purpose of the Study:
- To evaluate the utility of Lp(a) as an ASCVD risk-enhancing factor.
- To determine if C-reactive protein (CRP) modifies the association between elevated Lp(a) and ASCVD risk.
- To assess Lp(a) as a predictor of 10-year ASCVD risk in intermediate-risk individuals.
Main Methods:
- Analysis of Lp(a), hs-CRP, and other ASCVD risk factors in 15,933 participants from three large cohort studies.
- 10-year follow-up for incident ASCVD (coronary heart disease or stroke) and coronary heart disease (CHD).
- Statistical analysis including hazard ratios (HR) and confidence intervals (CI) to assess risk and interactions.
Main Results:
- The highest Lp(a) category (≥50 mg/dL) showed significantly increased ASCVD (HR=1.31) and CHD (HR=1.49) incidence compared to the lowest category (<10 mg/dL).
- Elevated Lp(a) independently predicted 10-year ASCVD risk in intermediate-risk individuals (HR=1.32).
- A significant interaction between Lp(a) and hs-CRP was observed, with the highest ASCVD risk in individuals with both elevated levels.
Conclusions:
- Elevated Lp(a) levels are associated with increased ASCVD risk.
- The ASCVD risk associated with elevated Lp(a) is particularly pronounced in individuals with concomitantly elevated hs-CRP levels.
- Lp(a) is a valuable risk-enhancing factor for identifying individuals at higher risk of ASCVD, especially those at intermediate risk and with elevated inflammation markers.
Abstract:
Background/Objectives: Elevated lipoprotein(a) [Lp(a)] is associated with increased incidence of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the utility of Lp(a) as an ASCVD risk-enhancing factor, as recommended by the 2019 ACC/AHA guidelines on ASCVD primary prevention, and to determine whether C-reactive protein (CRP) modifies the association of elevated Lp(a) with ASCVD risk. Methods: Lp(a), high sensitivity CRP (hs-CRP), and other ASCVD risk factors, including blood lipids, blood pressure, diabetes status, body weight and height, and smoking, were measured in 15,933 participants (median age 61.7 years with 25th-75th percentiles 57-68 years, 56.7% female, 19.7% Black, free of ASCVD at baseline) in the Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and Multi-Ethnic Study of Atherosclerosis. Participants were followed for 10 years for incident ASCVD (coronary heart disease (CHD) or stroke) and CHD (including angioplasty and/or coronary artery bypass but minus stroke). These endpoints occurred in 9.7% and 7.4% of subjects, respectively. Results: Compared with the lowest Lp(a) category (<10 mg/dL), the highest Lp(a) category (≥50 mg/dL) carried a significantly increased incidence of ASCVD (hazard ratio [HR] = 1.31; 95% confidence interval [CI] 1.15-1.50; p < 0.001) and CHD (HR = 1.49; 95%CI 1.27-1.75; p < 0.001). The association of elevated Lp(a) with incident ASCVD was stronger in males and non-Black individuals and was independent of diabetes status. Lp(a) levels ≥ 50 mg/dL predicted the 10-year ASCVD risk for those at intermediate risk (≥7.5%, HR = 1.32; 95%CI 1.15-1.52; p < 0.001). There was a significant interaction between Lp(a) and hs-CRP; individuals with concomitant elevated levels of Lp(a) and hs-CRP had the highest ASCVD risk. Conclusions: Elevated Lp(a) levels were associated with increased ASCVD risk, particularly in individuals with concomitantly elevated hs-CRP levels and those at intermediate 10-year ASCVD risk.
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