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Associations Between High-Density Lipoprotein Particles and Ischemic Events by Vascular Domain, Sex, and Ethnicity: A Pooled Cohort Analysis.

  • Singh, Kavisha1
  • Chandra, Alvin1
  • Sperry, Thomas1
  • Joshi, Parag H1
  • Khera, Amit1
  • Virani, Salim S2
  • Ballantyne, Christie M3
  • Otvos, James D4
  • Dullaart, Robin P F5
  • Gruppen, Eke G5
  • Connelly, Margery A4
  • Ayers, Colby R1
  • Rohatgi, Anand1
  • 1 University of Texas Southwestern Medical Center, Dallas (K.S., A.C., T.S., P.H.J., A.K., C.R.A., A.R.).
  • 2 Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.).
  • 3 Baylor College of Medicine, Houston, TX (S.S.V., C.M.B.).
  • 4 Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC (J.D.O., M.A.C.).
  • 5 University of Groningen and University Medical Center Groningen, The Netherlands (R.P.F.D., E.G.G.). , (Netherlands)
Published Article
Ovid Technologies Wolters Kluwer -American Heart Association
Publication Date
Aug 18, 2020
DOI: 10.1161/CIRCULATIONAHA.120.045713
PMID: 32804568


High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C. We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke. In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52-0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61-0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35-0.69]; for Blacks, 1.22 [95% CI, 0.76-1.98]; Pinteraction=0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36-0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08-2.83]; Pinteraction<0.0001). Compared with HDL-C, HDL-P was consistently associated with MI and ischemic stroke in the overall population. Differential associations of both HDL-C and HDL-P for MI by Black ethnicity suggest that atherosclerotic cardiovascular disease risk may differ by vascular domain and ethnicity. Future studies should examine individual outcomes separately.

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