High Lp(a) doubles coronary heart disease risk only in people with elevated Factor VIII or hs-CRP, an interaction found in 6,495 MESA participants (J Clin Lipidol 2023)

Original title: Incident CHD and ischemic stroke associated with lipoprotein(a) by levels of Factor VIII and inflammation

J Clin Lipidol · 1 January 2023 · 7

Colantonio LD, Goonewardena SN, Wang Z, Jackson EA, Farkouh ME, Li M, Malick W, Kent ST, López JAG, Muntner P, Bittner V, Rosenson RS

In 6,495 MESA participants aged 45-84 without baseline atherosclerotic cardiovascular disease, followed a median 13.9 years (390 coronary heart disease and 247 ischaemic stroke events), high Lp(a) (>=40.1 vs <40.1 mg/dL) was associated with coronary heart disease (CHD) risk only among those with high coagulation Factor VIII (HR 2.00, 95% CI 1.33-3.01) but not low Factor VIII (HR 1.07, 95% CI 0.80-1.44; P for interaction 0.016), and similarly only among those with high hs-CRP (HR 2.00, 95% CI 1.29-3.09) but not low hs-CRP (HR 1.16, 95% CI 0.87-1.54; P for interaction 0.042). Lp(a) was not associated with ischaemic stroke regardless of Factor VIII or hs-CRP levels. The findings show high Lp(a) is a CHD risk factor specifically in adults with elevated hemostatic or inflammatory markers, suggesting these pathways interact to drive its cardiovascular risk.

Original abstract

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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.