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The Additive Prognostic Value of Lipoprotein(a) for All-cause and Cardiovascular Mortality Across the Traditional
Mustafa Al-Jarshawi1, Nicholas Chew2, Marc P Bonaca3
1Keele Cardiovascular Research Group, Centre for Prognosis Research, Keele University, Keele, UK.
Insights
Elevated Lipoprotein(a) (Lp(a)) levels significantly increase cardiovascular mortality risk in high-risk individuals. This finding emphasizes Lp(a) testing for personalized cardiovascular risk assessment.
Area of Science:
- Cardiovascular Medicine
- Clinical Risk Stratification
- Biomarker Research
Background:
- Lipoprotein(a) (Lp(a)) is a recognized independent risk factor for cardiovascular (CV) outcomes.
- The prognostic significance of Lp(a) across different levels of traditional CV risk is not well-established.
- Understanding Lp(a)'s role in varied risk strata is crucial for refining CV risk prediction.
Purpose of the Study:
- To evaluate the association between Lp(a) levels and all-cause and CV mortality.
- To stratify this association based on baseline traditional CV risk.
- To determine if Lp(a) provides incremental prognostic value in different risk groups.
Main Methods:
- Analysis of a nationally representative US adult cohort from NHANES III (1988-1994) with mortality follow-up through 2019.
- Stratification of baseline CV risk using the PREVENT equations (low, borderline-intermediate, high).
- Application of multivariable Cox and Fine-Gray competing risk models to assess Lp(a) and mortality associations.
Main Results:
- Elevated Lp(a) (>50 mg/dL) was more prevalent in the high-risk group.
- In high-risk individuals, Lp(a) >75 mg/dL was linked to increased all-cause (HR: 1.25) and CV mortality (sHR: 1.21).
- No significant associations were found in lower-risk groups, indicating risk-specific prognostic value.
Conclusions:
- High Lp(a) levels (>75 mg/dL) are independently associated with increased all-cause and CV mortality in individuals with high baseline CV risk.
- Lp(a) demonstrates significant prognostic utility, particularly in high-risk populations.
- These findings support the clinical value of assessing Lp(a) for enhanced CV risk stratification.
Introduction:
Lp(a) is an independent risk factor for a variety of cardiovascular (CV) outcomes. However, it remains unclear whether its prognostic value differs between individuals with varying baseline traditional CV risk. This study aims to evaluate the association between Lp(a) levels and all-cause & CV mortality, stratified by baseline CV risk.
Methods:
Using data from NHANES III (1988-1994) with mortality follow-up through 2019, we analysed a nationally representative cohort of U.S. adults. Baseline CV risk was stratified into low, borderline-intermediate, and high groups using the PREVENT equations. Associations between Lp(a) levels and outcomes were assessed using multivariable Cox and Fine-Gray competing risk models.
Results:
A total of 55,050,155 survey-weighted records (4,707 unweighted) were analysed. The mean age was 48 (±13) years, with 51% female. Over a mean follow-up of 22.4 years (±7.07), there were 17,301,805 all-cause and 4,965,456 CV deaths. Elevated Lp(a) (>50 mg/dL) was present in 15% overall, more commonly in the high-risk group (15% vs 11% in low-risk). In the high-risk group, Lp(a) >75 mg/dL was associated with higher all-cause (HR: 1.25; 95% CI: 1.02-1.53) and CV mortality (sHR: 1.21; 95% CI: 1.09-1.36). Lp(a) 50-75 mg/dL showed a borderline association with all-cause mortality (HR: 1.16; 95% CI: 1.00-1.34) but not CV mortality (sHR: 1.06; 95% CI: 0.98-1.15). No significant associations were observed in lower-risk groups.
Conclusions:
Elevated Lp(a) levels (> 75 mg/dL) are associated with increased all-cause and CV mortality among individuals with high baseline traditional CV risk, as defined by the AHA's PREVENT score, independent of traditional risk factors. Our findings highlight the value of Lp(a) particularly among those with elevated baseline risk, where its prognostic utility appears greatest.
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