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Background  In 2013 American College of Cardiology and the American Heart Association released a guideline on the management of atherosclerotic cardiovascular disease (ASCVD) including a composite of death from CVD, non-fatal myocardial infarction, or non-fatal stroke (hard CVD). This guideline recommended a risk score that was calculated using pooled cohort equations (ASCVD-PCE). The guideline was updated in 2018/2019 and further risk discussion was suggested for deciding whether to continue or initiate statin therapy among non-diabetic individuals with ASCVD-PCE score ranged 5–20%. They recommended a risk discussion with considering risk enhancing factors (ASCVD-REFs) including family history of premature CVD, chronic kidney disease, triglycerides ≥ 175 mg/dl, low-density lipoprotein cholesterol (LDL-C) ≥ 160 mg/dl, metabolic syndrome (Mets), and for women premature menopause, and hypertensive disorders of pregnancy (HDP). In the current study, we aimed to examine the predictability of recommended ASCVD-REFs on incident hard CVD in non-diabetic individuals with LDL-C 70-189 mg/dl, with ASCVD-PCE risk 5–20% during 10 and 15-year follow-up.    Methods   A mong a total of 3546 non-diabetic individuals aged 40-75 years, after excluding those with ASCVD-PCE score < 5% and ≥ 20% (n = 2342), 1204 individuals (women = 332) were included. The univariable and multivariable (further adjusted for ASCVD-PCE) Cox regression analysis were used to evaluate the association of each potential ASCVD-REFs with hard CVD. Additionnaly, the role of different components of Mets and a history of gestational diabetes (GDM)/macrosomia was also examined. The predictive ability of each significant ASCVD-REFs, then was evaluated by the discrimination accuracy and risk reclassification index.    Results  During the 10-year follow-up, 73 hard CVD events occurred. Although in univariable analysis, high blood pressure (BP) component of Mets, GDM/macrosomia, and HDP remained as significant ASCVD-REFs, in the multivariable analysis, only the history of HDP (5.35 (1.22–23.38)) and GDM/macrosomia (3.18 (1.05–9.65)) showed independent risks. During the 15-year follow-up, Mets (1.47 (1.05–2.06)) and its components of high waist circumference (1.40 (1.0–1.95)) and high BP (1.52 (1.07–2.15)) significantly increased the risk. These ASCVD-REFs did not improve discrimination or predictive ability.    Conclusions  In a decade follow-up, only conditions specific for women and in longer follow-up, the presence of Mets perse, and its components of high WC and high BP were shown as significant ASCVD-REFs.

The risk and added values of the atherosclerotic cardiovascular risk enhancers on prediction of cardiovascular events: Tehran lipid and glucose study