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. 2022 Mar 1;79(8):757-768.
doi: 10.1016/j.jacc.2021.11.058.

Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk

Anurag Mehta  1 , Nestor Vasquez  2 , Colby R Ayers  3 , Jaideep Patel  4 , Ananya Hooda  1 , Amit Khera  5 , Roger S Blumenthal  6 , Michael D Shapiro  7 , Carlos J Rodriguez  8 , Michael Y Tsai  9 , Laurence S Sperling  1 , Salim S Virani  10 , Michael J Blaha  6 , Parag H Joshi  11
Affiliations

Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk

Anurag Mehta et al. J Am Coll Cardiol. .

Abstract

Background: Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination.

Objectives: This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk.

Methods: Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor-adjusted Cox regression models.

Results: Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS.

Conclusions: Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions.

Keywords: atherosclerotic cardiovascular disease; coronary artery calcium; lipoprotein(a); primary cardiovascular disease prevention.

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Conflict of interest statement

Funding Support and Author Disclosures The MESA study is 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. The DHS study was funded by the Donald W. Reynolds Foundation, Las Vegas, Nevada, and partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105. Dr Virani has received grant support from the Department of Veterans Affairs, the World Heart Federation, and the Tahir and Jooma Family; has received honorarium from American College of Cardiology (Associate Editor for Innovations, acc.org). Dr Joshi has received grant support from the American Heart Association, NASA, and Novo Nordisk; has received consulting income from Bayer and Regeneron; owns equity in G3 Therapeutics; and has served as a site investigator with all funds to the institution from GlaxoSmithKline, Sanofi, AstraZeneca, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.. Ten-year ASCVD Incidence across lipoprotein(a) (quintiles 1-4, quintile 5) and CAC (0, 1-99, ≥100) groups
The highest 10-year atherosclerotic cardiovascular disease (ASCVD) incidence among MESA participants was seen in the lipoprotein(a) [Lp(a)] quintile 5 with coronary artery calcium (CAC) ≥ 100 group, while the lowest 10-year ASCVD incidence was evidenced in the Lp(a) quintiles 1-4 with CAC 0 group. A higher 10-year ASCVD incidence was apparent in the Lp(a) quintile 5 group when compared to Lp(a) quintiles 1-4 group only among participants with CAC ≥ 100.
Figure 2.
Figure 2.. Cumulative ASCVD Incidence across lipoprotein(a) (quintiles 1-4, quintile 5) and CAC (0, 1-99, ≥100) groups.
The Kaplan-Meier survival curves for MESA participants illustrates the highest ASCVD incidence in the Lp(a) quintile 5 with CAC ≥ 100 group. Among participants with CAC 0 and 1-99 no difference in ASCVD risk was seen between Lp(a) quintile 5 versus Lp(a) quintiles 1-4 group. Abbreviations as in Figure 1.
Figure 3.
Figure 3.. Cumulative ASCVD Incidence across lipoprotein(a) (< 50 mg/dL, ≥ 50 mg/dL) and CAC (<100 AU, ≥100 AU) groups.
The Kaplan-Meier survival curves for MESA participants illustrates the highest ASCVD incidence in the Lp(a) ≥ 50 mg/dL with CAC ≥ 100 group. For participants with CAC score < 100 AU no difference in cumulative ASCVD incidence was seen between the Lp(a) ≥ 50 mg/dL and < 50 mg/dL groups. Abbreviations as in Figure 1.
Central Illustration.
Central Illustration.. Joint association of Lp(a) and CAC score with ASCVD risk.
Individuals with elevated Lp(a) and CAC score are the highest ASCVD risk. Elevated Lp(a) level does not stratify ASCVD risk further among those with low CAC score.
See this image and copyright information in PMC

Comment in

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