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Incident CHD and ischemic stroke associated with lipoprotein(a) by levels of Factor VIII and inflammation
Lisandro D Colantonio1, Sascha N Goonewardena2, Zhixin Wang1
1Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA (Drs Colantonio, Wang, Li, Muntner, Rosenson).
Insights
High lipoprotein(a) significantly increases coronary heart disease risk in individuals with elevated inflammation or coagulation markers. This finding highlights the importance of considering these factors when assessing cardiovascular disease risk.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Epidemiology
Background:
- Elevated lipoprotein(a) is linked to increased atherosclerotic cardiovascular disease (ASCVD) risk.
- Inflammation and coagulation pathways may mediate this association.
- High-sensitivity C-reactive protein (hs-CRP) levels modulate the lipoprotein(a)-ASCVD relationship.
Purpose of the Study:
- To investigate the association between lipoprotein(a) and incident ASCVD.
- To examine this association in relation to Factor VIII levels, a marker of coagulation.
- To control for hs-CRP, a marker of inflammation, in the analysis.
Main Methods:
- Analysis of data from 6,495 Multi-Ethnic Study of Atherosclerosis (MESA) participants (aged 45-84).
- Baseline measurements of lipoprotein(a), Factor VIII activity, and hs-CRP.
- Follow-up for incident coronary heart disease (CHD) and ischemic stroke through 2015.
Main Results:
- High lipoprotein(a) was associated with a 2.00-fold increased risk of CHD in participants with high Factor VIII levels (p-interaction=0.016).
- High lipoprotein(a) was associated with a 2.00-fold increased risk of CHD in participants with high hs-CRP levels (p-interaction=0.042).
- No significant association was found between lipoprotein(a) and ischemic stroke, irrespective of Factor VIII or hs-CRP levels.
Conclusions:
- High lipoprotein(a) is a significant risk factor for coronary heart disease.
- This risk is particularly pronounced in individuals with elevated hemostatic (Factor VIII) or inflammatory (hs-CRP) markers.
- Lipoprotein(a)'s role in ischemic stroke risk appears independent of these markers.
Background:
Inflammation and coagulation may contribute to the increased risk for atherosclerotic cardiovascular disease (ASCVD) associated with high lipoprotein(a). The association of lipoprotein(a) with ASCVD is stronger in individuals with high versus low high-sensitivity C-reactive protein (hs-CRP), a marker of inflammation.
Objectives:
Determine the association of lipoprotein(a) with incident ASCVD by levels of coagulation Factor VIII controlling for hs-CRP.
Methods:
We analyzed data from 6,495 men and women 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA) without prevalent ASCVD at baseline (2000-2002). Lipoprotein(a) mass concentration, Factor VIII coagulant activity, and hs-CRP were measured at baseline and categorized as high or low (≥75th or <75th percentile of the distribution). Participants were followed for incident coronary heart disease (CHD) and ischemic stroke through 2015.
Results:
Over a median follow-up of 13.9 years, there were 390 CHD and 247 ischemic stroke events. The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) (≥40.1 versus <40.1 mg/dL) including adjustment for hs-CRP among participants with low and high Factor VIII was 1.07 (0.80-1.44) and 2.00 (1.33-3.01), respectively (p-value for interaction 0.016). The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) including adjustment for Factor VIII was 1.16 (0.87-1.54) and 2.00 (1.29-3.09) among participants with low and high hs-CRP, respectively (p-value for interaction 0.042). Lp(a) was not associated with ischemic stroke regardless of Factor VIII or hs-CRP levels.
Conclusion:
High lipoprotein(a) is a risk factor for CHD in adults with high levels of hemostatic or inflammatory markers.
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