A comparative assessment of non-laboratory-based versus commonly used laboratory-based cardiovascular disease risk scores in the NHANES III population

Abstract

Background: National and international primary CVD risk screening guidelines focus on using total CVD risk scores. Recently, we developed a non-laboratory-based CVD risk score (inputs: age, sex, smoking, diabetes, systolic blood pressure, treatment of hypertension, body-mass index), which can assess risk faster and at lower costs compared to laboratory-based scores (inputs include cholesterol values). We aimed to assess the exchangeability of the non-laboratory-based risk score to four commonly used laboratory-based scores (Framingham CVD [2008, 1991 versions], and Systematic COronary Risk Evaluation [SCORE] for low and high risk settings) in an external validation population.

Methods and findings: Analyses were based on individual-level, score-specific rankings of risk for adults in the Third National Health and Nutrition Examination Survey (NHANES III) aged 25-74 years, without history of CVD or cancer (n = 5,999). Risk characterization agreement was based on overlap in dichotomous risk characterization (thresholds of 10-year risk >10-20%) and Spearman rank correlation. Risk discrimination was assessed using receiver operator characteristic curve analysis (10-year CVD death outcome). Risk characterization agreement ranged from 91.9-95.7% and 94.2-95.1% with Spearman correlation ranges of 0.957-0.980 and 0.946-0.970 for men and women, respectively. In men, c-statistics for the non-laboratory-based, Framingham (2008, 1991), and SCORE (high, low) functions were 0.782, 0.776, 0.781, 0.785, and 0.785, with p-values for differences relative to the non-laboratory-based score of 0.44, 0.89, 0.68 and 0.65, respectively. In women, the corresponding c-statistics were 0.809, 0.834, 0.821, 0.792, and 0.792, with corresponding p-values of 0.04, 0.34, 0.11 and 0.09, respectively.

Conclusions: Every score discriminated risk of CVD death well, and there was high agreement in risk characterization between non-laboratory-based and laboratory-based risk scores, which suggests that the non-laboratory-based score can be a useful proxy for Framingham or SCORE functions in resource-limited settings. Future external validation studies can assess whether the sex-specific risk discrimination results hold in other populations.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Agreement in risk characterization between Framingham (2008) CVD and non-laboratory-based risk scores.

Rank variables for the non-laboratory-based risk score are plotted against rank variables for the Framingham (2008) CVD score for adults aged 25–74 years with complete data in the NHANES III population without history of MI, heart failure, stroke or cancer. Larger ranks indicate greater CVD risk. Size of bubbles correspond to NHANES III sampling weights (i.e., larger bubbles indicate more individuals represented by sample weight). Based on a risk threshold that corresponds to 10-year CHD risk (i.e., top 42.2% of men and 18.8% of women in the sample), 91.9% of men (Panel A) and 94.6% of women (Panel B) would be similarly characterized as high or low risk by the non-laboratory-based and Framingham (2008) CVD risk scores.

Figure 2. ROC curves (10-year CVD death outcome) for non-laboratory-based and Framingham (2008) CVD risk scores.

Receiver operator characteristic (ROC) curves for the non-laboratory-based (“non-lab”) and Framingham (2008) CVD (“fram cvd”) scores, with 10-year CVD death as the outcome of interest, for individuals with complete data. For men (Panel A), the performances in risk discrimination, as assessed by the c-statistic (i.e., area under the ROC curve) and 95% CI, were 0.782 (0.739–0.825) and 0.776 (0.733–0.819) for the non-laboratory-based and Framingham (2008) CVD risk scores, respectively, with a p-value for the difference of 0.44. For women (Panel B), the c-statistics and 95% CI were 0.809 (0.751–0.866) and 0.834 (0.782–0.885) for the non-laboratory-based and Framingham (2008) CVD risk scores, respectively, with a p-value for the difference of 0.04.