The WHO Cardiovascular Disease Risk (Non-Laboratory-Based) in a Selected Brazilian Population: Percentiles of Distribution And Agreement With Laboratory-Based Scores

the corresponding percentile for sex and age.


Introduction
In 2019, the World Health Organization (WHO) published revised charts for estimating the 10-year risk of cardiovascular disease (CVD). 1 Two models are proposed: one based on laboratory tests including plasma total cholesterol and presence or absence of diabetes mellitus as predictors, and another based on the body mass index (BMI).In lowresource and office settings, when cholesterol levels and information on diabetes are not available, the BMI-based score can be used. 2 a previous study, we determined laboratory-based percentiles of the WHO CVD risk distribution, according to sex and age, in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline population. 3These percentiles were associated with the calculated risk of atherosclerotic CVD up to 75 years, regardless of the estimated 10-year risk.[5] In this study, we sought to (1) determine sex-and agespecific percentiles of the distribution of the WHO nonlaboratory-based CVD risk in the Brazilian population and (2) evaluate the agreement between WHO laboratory-and non-laboratory-based CVD risk scores.

Methods
This study is a cross-sectional analysis of ELSA-Brasil baseline data collected from 2008 to 2010.ELSA-Brasil is a prospective cohort of 15,105 racially mixed employees from public universities and research institutions in six Brazilian cities. 6,7 We included participants from 40 to 74 years old and excluded those with previous myocardial infarction, stroke, or revascularization procedures.The protocol for ELSA-Brasil was approved by the ethics committee of each participating institution, and all participants provided written informed consent.
Hypertension was considered in the presence of systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or the use of medication to control blood pressure.Diabetes mellitus was defined as a self-reported diagnosis, use of specific medication, fasting blood glucose ≥126 mg/dL, glycated hemoglobin ≥6.5%, or a 2-hour blood glucose ≥200 mg/dL after 75 g load on oral glucose tolerance test.Detailed definitions of other variables reported in this study can be found elsewhere. 3Plasma total cholesterol levels and BMI were categorized according to the groups used for the WHO CVD risk calculation. 1,2n-year risk of experiencing a first fatal or nonfatal CVD event (related to coronary heart disease or stroke) was computed using the 2019 Updated WHO CVD risk charts calibrated for Tropical Latin America. 1,2 establish percentiles of the WHO non-laboratorybased CVD risk score distribution, we first sorted all possible values of the calculated risk within each age group.Then, we determined the distribution percentile corresponding to each score.Separate analyses were performed for each sex.
The sign test was applied to compare risk scores once differences between paired observations were not symmetric.A p-value < 0.05 was considered statistically significant.Agreement between risk values was assessed using Bland-Altman diagrams.All analyses were performed using R software and Microsoft Excel.The Shiny R package was used to develop a web application for calculating the 10-year CVD risk and the corresponding percentile for sex and age.

Results
The study population (n = 13,366) was characterized by a higher female presence (55%) and a median age (interquartile range [IQR]) of 52 (46, 59) years (Supplemental Figure 1, Supplemental Table 1).Supplemental Figure 2 shows the predicted 10-year CVD risk distribution according to sex and age group, while Supplemental Tables 2 to 8 report the percentiles of such distribution.These percentiles enabled the construction of risk-versus-percentile plots according to sex and age group (Figure 1).

Males
Overall, the BMI-based risk was slightly lower than the risk based on laboratory exams (median [IQR] 3% [2%, 5%] versus 4% [2%, 6%], respectively, p <0.001).Figure 2 shows the agreement between laboratory-and non-laboratorybased risk scores in females and males.The scores agreed in most participants (7,884 [59%]).The difference between the values (laboratory-based risk minus non-laboratorybased risk) ranged from -3% to 7% in females and from -5% to 17% in males.Supplemental Figures 3 to 5 depict the agreement between laboratory-and non-laboratory-based risk scores according to subgroups of interest.Among individuals without diabetes mellitus, the values were the same in 7,873 (70.5%), whereas the laboratory-based risk was numerically higher than the BMI-based risk in 2,176 (99.5%) participants with diabetes.The higher the total cholesterol level and the lower the BMI, the greater the tendency for a higher laboratory-based risk compared to non-laboratory-based risk.
A web application for calculating CVD risks and percentiles by sex and age can be accessed at https://bit.ly/3sGsIgK.An R code for creating new variables for WHO laboratory-and BMI-based CVD risks and the corresponding percentiles for sex and age in a dataset is available at https://bit.ly/3Pov250.

Discussion
BMI-based CVD risk assessment serves as an option when cholesterol level and glycemic exams are unavailable 2 and may offer community members a simpler method to calculate their own risk.Our findings indicate that BMIbased risk generally agrees with laboratory-based risk, but may be substantially lower in the presence of diabetes mellitus and very high total cholesterol.It is feasible to hypothesize that the non-laboratory-based risk score underestimates actual risk in these high-risk subgroups.However, definitive conclusions cannot be drawn once score performance metrics were not evaluated.We also observed that the BMI-based risk tends to be lower than the laboratory-based score as the BMI decreases.The question of which score is more accurate among individuals with low BMI remains unanswered.
Limitations of this study include the fact that the study population is not representative of the Brazilian population, with a higher female proportion, more white and less brown

Figure 1 -Figure 2 -
Figure 1 -Percentiles of the predicted 10-year cardiovascular disease (CVD) risk distribution, according to sex and age group.The CVD risk was calculated using the non-laboratory-based risk score from the World Health Organization.