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Remnant cholesterol and the risk of aortic valve calcium progression: insights from the MESA study
Ze-Hua Li1, Qing-Yun Hao1, Yu-Hong Zeng2
1Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Insights
Elevated remnant cholesterol (RC) is a significant risk factor for aortic valve calcium (AVC) progression in individuals without cardiovascular disease. This finding highlights RC as a potential target for primary prevention strategies.
Area of Science:
- Cardiology
- Atherosclerosis Research
- Lipid Metabolism
Background:
- Remnant cholesterol (RC) is linked to cardiovascular disease risk.
- Limited population studies exist on RC's association with aortic valve calcium (AVC) progression.
- The precise role of RC in AVC progression remains unclear.
Purpose of the Study:
- To investigate the association between remnant cholesterol (RC) levels and the progression of aortic valve calcium (AVC).
- To evaluate RC as a potential residual risk factor for AVC progression in individuals without established atherosclerotic cardiovascular disease.
- To compare the risk of AVC progression between different levels of RC and low-density lipoprotein cholesterol (LDL-C).
Main Methods:
- Analysis of 5597 individuals from the Multi-Ethnic Study of Atherosclerosis database without baseline atherosclerotic cardiovascular disease.
- Calculation of RC using the Martin/Hopkins equation (Total Cholesterol - HDL-C - LDL-C).
- Adjusted Cox regression analyses and discordance analyses between RC and LDL-C levels were performed.
Main Results:
- During a median follow-up of 2.4 years, 10.1% of participants showed AVC progression.
- Elevated RC levels (third and fourth quartiles) were associated with increased risk of AVC progression (HRs 1.322-1.546).
- Individuals with high RC and low LDL-C had a significantly higher risk of AVC progression compared to those with low RC and low LDL-C (HR 1.528).
Conclusions:
- Elevated remnant cholesterol (RC) is an independent residual risk factor for aortic valve calcium (AVC) progression in individuals free of atherosclerotic cardiovascular disease.
- The findings suggest that RC may play a causal role in AVC development.
- Further research is warranted to explore targeted reduction of RC for primary cardiovascular disease prevention.
Background:
Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous.
Methods:
From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups.
Results:
During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses.
Conclusions:
In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration.
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