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Lipoprotein (a) and Incident Coronary Heart Disease in the Community: Impact of Traditional Cardiovascular Risk
Natalie Arnold1,2,3, Alina Goßling1,3, Benjamin Bay1,2,3
1Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg; Hamburg, Germany.
Insights
High Lipoprotein (a) (Lp(a)) increases coronary heart disease (CHD) risk, even in individuals with few cardiovascular risk factors. This finding presents challenges for mitigating Lp(a)-associated CHD risk in low-risk populations.
Area of Science:
- Cardiology
- Preventive Medicine
- Genetics
Background:
- Lipoprotein (a) (Lp(a)) is an independent risk factor for cardiovascular disease.
- The impact of elevated Lp(a) on coronary heart disease (CHD) risk in relation to traditional cardiovascular risk factors (CVRFs) is not fully understood.
- Understanding this relationship is crucial for effective risk stratification and prevention strategies.
Purpose of the Study:
- To investigate the association between high Lp(a) levels and incident CHD in a general population.
- To examine how this association varies based on the presence or absence of major modifiable CVRFs (hypertension, diabetes, hypercholesterolemia, smoking).
- To assess the CHD risk conferred by high Lp(a) in individuals with low versus increased CVRF burden.
Main Methods:
- Analysis of data from 66,495 CHD-free individuals across eight European prospective population-based cohorts.
- Stratification of the cohort into "0/1 CVRF" (low risk) and "≥2 CVRFs" (increased risk) groups based on baseline CVRF status.
- Utilized Fine and Gray competing risk-adjusted models to assess the association between Lp(a) mass (≥90th percentile) and incident CHD events.
Main Results:
- Over a median follow-up of 9.7 years, 3,467 incident CHD events were recorded.
- Individuals with 0/1 CVRF and elevated Lp(a) showed a strong association with future CHD events, comparable to those with ≥2 CVRFs.
- Fully-adjusted models revealed sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) of 1.38 (95% CI, 1.12-1.71) in the 0/1 CVRF group and 1.27 (95% CI, 1.10-1.46) in the ≥2 CVRFs group.
Conclusions:
- High Lp(a) levels are associated with an increased risk of adverse cardiovascular outcomes, even in individuals with no or only one traditional CVRF.
- Elevated Lp(a) poses a significant risk for CHD, irrespective of the overall burden of modifiable cardiovascular risk factors.
- These findings highlight the challenges in mitigating Lp(a)-associated CHD risk, particularly within low-risk populations, emphasizing the need for targeted interventions.
Aims:
Deleterious effects Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline.
Methods:
Overall 66,495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in "0/1 CVRF" (low risk; n= 41,770) and"≥2 CVRFs" (increased risk; n=24,725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th versus ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events.
Results:
During a median follow-up of 9.7 years, 3,467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95% CI, 1.12-1.71) versus 1.27 (95% CI, 1.10-1.46) in those having 0/1 versus ≥2 CVRFs at baseline (Pinteraction0.50).
Conclusion:
Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.
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