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

Lisandro D Colantonio; Sascha N Goonewardena; Zhixin Wang; Elizabeth A Jackson; Michael E Farkouh; Mei Li; Waqas Malick; Shia T Kent; J Antonio G López; Paul Muntner; Vera Bittner; Robert S Rosenson

doi:10.1016/j.jacl.2023.06.001

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

J Clin Lipidol. 2023 Jul-Aug;17(4):529-537. doi: 10.1016/j.jacl.2023.06.001. Epub 2023 Jun 10.

Authors

Affiliations

¹ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA (Drs Colantonio, Wang, Li, Muntner, Rosenson). Electronic address: lcolantonio@uab.edu.
² Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA (Dr Goonewardena).
³ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA (Drs Colantonio, Wang, Li, Muntner, Rosenson).
⁴ Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA (Drs Jackson, Bittner).
⁵ Peter Munk Cardiac Centre, University of Toronto and Heart and Stroke Richard Lewar Centre of Excellence, Toronto, ON, Canada (Dr Farkouh).
⁶ Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA (Drs Malick, Rosenson).
⁷ Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA (Dr Kent).
⁸ Global Development, Amgen Inc., Thousand Oaks, CA, USA (Dr López).

PMID: 37331900
DOI: 10.1016/j.jacl.2023.06.001

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 (≥75^th or <75^th 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.

Keywords: Adults; Blood coagulation; Coronary heart disease; Inflammation; Lipoprotein(a); Stroke.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Atherosclerosis* / complications
Biomarkers
C-Reactive Protein / analysis
Coronary Disease* / complications
Coronary Disease* / epidemiology
Factor VIII
Female
Hemostatics*
Humans
Inflammation / complications
Ischemic Stroke* / complications
Lipoprotein(a)
Male
Risk Factors
Stroke* / complications
Stroke* / epidemiology

Substances

C-Reactive Protein
Factor VIII
Lipoprotein(a)
Hemostatics
Biomarkers