Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA

Rishi Rikhi, Harpreet S. Bhatia, Christopher L. Schaich, Nicklaus Ashburn, Michael Y. Tsai, Erin D. Michos, Parag A. Chevli, David M. Herrington, Sotirios Tsimikas, Michael D. Shapiro

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1 Scopus citations


Background: This study explored the longitudinal relationship of Lp(a) (lipoprotein[a]) and hypertension to cardiovascular outcomes in a large multiethnic cohort free of baseline cardiovascular disease. Methods: Individuals from the MESA (Multi-Ethnic Study of Atherosclerosis; N=6674) were grouped as follows: group 1: Lp(a) <50 mg/dL and no hypertension; group 2: Lp(a) ≥50 mg/dL and no hypertension; group 3: Lp(a) <50 mg/dL and hypertension; and group 4: Lp(a) ≥50 mg/dL and hypertension. Kaplan-Meier curves and multivariable Cox proportional hazard models were used to assess the relationship of Lp(a) and hypertension with time to cardiovascular disease events. Results: Mean follow-up time was 13.9 (5.0) years and 809 participants experienced a cardiovascular disease event. A statistically significant interaction was found between Log[Lp(a)] and hypertension status (P=0.091). Compared with the reference group (Lp[a] <50 mg/dL and no hypertension), those with Lp[a] ≥50 mg/dL and no hypertension had no increased risk for cardiovascular disease events (hazard ratio, 1.09 [95% CI, 0.79-1.50]). However, those with Lp(a) <50 mg/dL and hypertension or Lp(a) ≥50 mg/dL and hypertension demonstrated a statistically significant increase in risk compared to the reference group (hazard ratio, 1.66 [95% CI, 1.39-1.98]) and (hazard ratio, 2.07 [95% CI, 1.63-2.62]), respectively. Among those with hypertension, Lp(a) was associated with a significant increase in cardiovascular disease risk (hazard ratio, 1.24 [95% CI, 1.01-1.53]). Conclusions: Although the major contribution to cardiovascular risk was hypertension, elevated Lp(a) significantly modified the association of hypertension with cardiovascular disease. More research is needed to understand mechanistic links among Lp(a), hypertension, and cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)352-360
Number of pages9
Issue number2
StatePublished - Feb 1 2023

Bibliographical note

Funding Information:
This research was supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS).

Funding Information:
R. Rikhi and N. Ashburn are supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL076132. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). H.S. Bhatia is supported by the National Institutes of Health, Grant 5T32HL079891, as part of the University of California San Diego Integrated Cardiovascular Epidemiology Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Michos reports Advisory Boards for Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Esperion, Novartis, Novo Nordisk and Pfizer. E.D. Tsimikas is a coinventor of and receives royalties from patents owned by University of California, San Diego, on oxidation-specific antibodies and of biomarkers related to oxidized lipoproteins; and is a co-founder and has an equity interest in Oxitope, Inc and its affiliates, Kleanthi Diagnostics, LLC, and Covicept Therapeutics, Inc. M.D. Shapiro has participated in scientific advisory boards with the following entities: Amgen; Novartis; Novo Nordisk; and has served as a consultant for Regeneron. The other authors report no conflicts.

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.


  • apolipoproteins
  • cardiovascular diseases
  • hypertension
  • lipoprotein(a)
  • risk

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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