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. 2024 Oct 25;19(10):e0312756.
doi: 10.1371/journal.pone.0312756. eCollection 2024.

Risk-enhancing factors and social determinants of health in risk assessment for atherosclerotic cardiovascular disease

Yiyi Zhang  1 , Jaejin An  2   3 , Mengying Xia  1 , Hui Zhou  2   3 , Yifei Sun  4 , Joanie Chung  2 , Mengnan Zhou  2 , Soon Kyu Choi  2 , Kerresa L Morrissette  2 , Paul Muntner  5 , Monika M Safford  6 , Carmen R Isasi  7 , Alka M Kanaya  8 , Brandon K Bellows  1 , Lisandro D Colantonio  5 , Kristi Reynolds  2   3 , Andrew E Moran  1
Affiliations

Risk-enhancing factors and social determinants of health in risk assessment for atherosclerotic cardiovascular disease

Yiyi Zhang et al. PLoS One. .

Abstract

Background: The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction.

Methods: We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70-189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs.

Results: We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%.

Conclusions: These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: LDC receives research support from Amgen, unrelated to this work.

Figures

Fig 1
Fig 1. Adjusted hazard ratios and population attributable fractions of ASCVD associated with each risk-enhancing factor and social determinants of health, pooled cohort.
Caption: AHRQ: Agency for Healthcare Research and Quality; ASCVD: atherosclerotic cardiovascular disease; HR: hazard ratio; PAF: population attributable fraction.
Fig 2
Fig 2. Adjusted hazard ratios and population attributable fractions of ASCVD associated with each risk-enhancing factor and social determinants of health, KPSC.
Caption: AHRQ: Agency for Healthcare Research and Quality; ASCVD: atherosclerotic cardiovascular disease; HR: hazard ratio; KPSC: Kaiser Permanente Southern California; PAF: population attributable fraction.
Fig 3
Fig 3. Differences in Harrell’s C-index and percent change in integrated Brier score comparing risk models with and without individual or combination of risk-enhancing factors and social determinants of health, pooled cohort.
Caption: * Multiple risk enhancers include family history of premature ASCVD, hypercholesterolemia, metabolic syndrome, CKD, hypertriglyceridemia, elevated hsCRP, and female conditions (in women only). † Multiple SDOH include no high school education, low household income, unemployment, neighborhood deprivation index, neighborhood low education, neighborhood low household income, neighborhood high poverty, neighborhood high unemployment. ‡ Multiple risk enhancers & SDOH include all the above. AHRQ: Agency for Healthcare Research and Quality; ASCVD: atherosclerotic cardiovascular disease; IBS: integrated Brier score.
Fig 4
Fig 4. Differences in Harrell’s C-index and percent change in integrated Brier score comparing risk models with and without individual or combination of risk-enhancing factors and social determinants of health, KPSC.
Caption: * Multiple risk enhancers include hypercholesterolemia, metabolic syndrome, CKD, chronic inflammatory condition, hypertriglyceridemia, and female conditions (in women only). † Multiple SDOH include neighborhood deprivation index, neighborhood low education, neighborhood low household income, neighborhood high poverty, neighborhood high unemployment. ‡ Multiple risk enhancers & SDOH include all the above. AHRQ: Agency for Healthcare Research and Quality; ASCVD: atherosclerotic cardiovascular disease; KPSC: Kaiser Permanente Southern California; IBS: integrated Brier score.
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