Clinical significance of zero coronary artery calcium in individuals with LDL cholesterol ≥190 mg/dL: The Multi-Ethnic Study of Atherosclerosis


      • Asymptomatic individuals with LDL-C ≥190 mg/dL are considered high-risk for future cardiovascular events.
      • Distribution of risk factors in these individuals is heterogeneous and varies by the presence or absence of CAC.
      • In MESA participants with LDL-C ≥190 mg/dL, younger age, female sex, and lack of diabetes were associated with absence of CAC.
      • Absence of CAC was independently associated with better cardiovascular outcomes in this MESA sub-group.
      • Absence of CAC may help ‘de-risk’ individuals in this high-risk patient population.


      Background and aims

      Individuals with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are considered high-risk and current guidelines recommend initiating high-intensity statin therapy in this group. We sought to examine the predictive ability of zero CAC in this high-risk group.


      Multi-Ethnic Study of Atherosclerosis participants without clinical cardiovascular disease and baseline LDL-C ≥190 mg/dL were identified. Cardiovascular risk factors were compared between those with CAC = 0 and CAC >0. Multivariable Poisson regression was used to identify predictors of CAC = 0. Association of CAC = 0 with incident cardiovascular events over a median follow-up of 13.2 years was examined using multivariable-adjusted Cox regression.


      246 individuals (mean age = 63 ± 9.4 years; 42% male; 31% white; 37% CAC = 0) with LDL-C ≥190 mg/dL were identified (mean LDL-C = 215 ± 27 mg/dL). Age <65 years (RR = 2.17, 95%CI = 1.49–3.23), female sex (RR = 2.10, 95%CI = 1.42–3.10), and no diabetes (RR = 2.22, 95%CI = 1.18–4.17) were associated with CAC = 0. Individuals with CAC = 0 had a lower risk for future cardiovascular events (incidence rate per 1000 person-years = 4.7; 10-year risk = 3.7%; risk/year = 0.4%) than those with CAC >0 (incidence rate per 1000 person-years = 26.4; 10-year risk = 20%; risk/year = 2.0%), adjusted HR 0.25 (95%CI = 0.10–0.66).


      Among persons with LDL-C ≥190 mg/dL, younger age, female sex, and the absence of diabetes were associated with CAC = 0. CAC = 0 was associated with a low risk of cardiovascular events, suggesting the utility of CAC assessment for stratifying risk in this high-risk group.

      Graphical abstract



      ASCVD (atherosclerotic cardiovascular disease), CAC (coronary artery calcium), CHD (coronary heart disease), Hs-CRP (high-sensitivity C-reactive protein), MESA (Multi-Ethnic Study of Atherosclerosis), RR (relative risk)
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      Linked Article

      • Very high LDL cholesterol: The power of zero passes another test
        AtherosclerosisVol. 292
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          In the current issue of Atherosclerosis, Sandesara et al. [1] shed additional light on the understanding of risk in individuals with very high LDL-C and no previous cardiovascular event identified in the Multiethnic Study of Atherosclerosis (MESA). Primary prevention strategies to reduce cardiovascular risk are mostly based on non-pharmacologic lifestyle modifications and pharmacologic management of individual risk factors such as hypertension, diabetes and, most importantly, hypercholesterolemia.
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