Coronary Artery Calcium Score and Polygenic Risk Score for the Prediction of Coronary Heart Disease Events.

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  • Additional Information
    • Source:
      Publisher: American Medical Association Country of Publication: United States NLM ID: 7501160 Publication Model: Print Cited Medium: Internet ISSN: 1538-3598 (Electronic) Linking ISSN: 00987484 NLM ISO Abbreviation: JAMA Subsets: MEDLINE
    • Publication Information:
      Original Publication: Chicago : American Medical Association, 1960-
    • Subject Terms:
      Atherosclerosis*/diagnostic imaging ; Coronary Disease*/diagnostic imaging; Aged ; Humans ; Middle Aged ; Calcium ; Coronary Vessels/diagnostic imaging ; Coronary Vessels/pathology ; Risk Factors ; Risk Assessment
    • Abstract:
      Importance: Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts.
      Objective: To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor-based model.
      Design, Setting, and Participants: Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands.
      Exposure: Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score.
      Main Outcomes and Measures: Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed.
      Results: The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, -0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years).
      Conclusions and Relevance: In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.
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    • Grant Information:
      N01 HC095168 United States HC NHLBI NIH HHS; UL1 TR001881 United States TR NCATS NIH HHS; UL1 TR001420 United States TR NCATS NIH HHS; N01 HC095165 United States HC NHLBI NIH HHS; R01 HL105756 United States HL NHLBI NIH HHS; N01 HC095169 United States HC NHLBI NIH HHS; R01 HL159250 United States HL NHLBI NIH HHS; N01 HC095166 United States HC NHLBI NIH HHS; UL1 TR001079 United States TR NCATS NIH HHS; P30 DK063491 United States DK NIDDK NIH HHS; UL1 TR000040 United States TR NCATS NIH HHS; N01 HC095167 United States HC NHLBI NIH HHS; R21 HL165376 United States HL NHLBI NIH HHS
    • Accession Number:
      SY7Q814VUP (Calcium)
    • Publication Date:
      Date Created: 20230523 Date Completed: 20230530 Latest Revision: 20231124
    • Publication Date:
      20240514
    • Accession Number:
      PMC10208141
    • Accession Number:
      10.1001/jama.2023.7575
    • Accession Number:
      37219552