A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): a pooled analysis of prospective cohorts and health examination surveys

Abstract

Background: Treatment of cardiovascular risk factors based on disease risk depends on valid risk prediction equations. We aimed to develop, and apply in example countries, a risk prediction equation for cardiovascular disease (consisting here of coronary heart disease and stroke) that can be recalibrated and updated for application in different countries with routinely available information.

Methods: We used data from eight prospective cohort studies to estimate coefficients of the risk equation with proportional hazard regressions. The risk prediction equation included smoking, blood pressure, diabetes, and total cholesterol, and allowed the effects of sex and age on cardiovascular disease to vary between cohorts or countries. We developed risk equations for fatal cardiovascular disease and for fatal plus non-fatal cardiovascular disease. We validated the risk equations internally and also using data from three cohorts that were not used to create the equations. We then used the risk prediction equation and data from recent (2006 or later) national health surveys to estimate the proportion of the population at different levels of cardiovascular disease risk in 11 countries from different world regions (China, Czech Republic, Denmark, England, Iran, Japan, Malawi, Mexico, South Korea, Spain, and USA).

Findings: The risk score discriminated well in internal and external validations, with C statistics generally 70% or more. At any age and risk factor level, the estimated 10 year fatal cardiovascular disease risk varied substantially between countries. The prevalence of people at high risk of fatal cardiovascular disease was lowest in South Korea, Spain, and Denmark, where only 5-10% of men and women had more than a 10% risk, and 62-77% of men and 79-82% of women had less than a 3% risk. Conversely, the proportion of people at high risk of fatal cardiovascular disease was largest in China and Mexico. In China, 33% of men and 28% of women had a 10-year risk of fatal cardiovascular disease of 10% or more, whereas in Mexico, the prevalence of this high risk was 16% for men and 11% for women. The prevalence of less than a 3% risk was 37% for men and 42% for women in China, and 55% for men and 69% for women in Mexico.

Interpretation: We developed a cardiovascular disease risk equation that can be recalibrated for application in different countries with routinely available information. The estimated percentage of people at high risk of fatal cardiovascular disease was higher in low-income and middle-income countries than in high-income countries.

Funding: US National Institutes of Health, UK Medical Research Council, Wellcome Trust.

Figure 1. Flowchart of inclusion and exclusion of cohort participants*

* HHP, MRFIT, and PRHHP include only men, and WHICT only women. † Only a subset of WHICT participants had cholesterol and fasting glucose measurements by design. ‡ Implausible data were considered as total cholesterol <1.75 or >20 mmol/L, systolic blood pressure <70 or >270 mmHg, and body mass index >80 kg/m².

Figure 2. Procedure for recalibration and application of the (fatal) CVD risk score

The figure shows the steps for applying the risk prediction equation for fatal CVD to individuals in different countries through recalibration. The figure uses the example of a 60-year-old man in the USA in 2011 with risk factor levels as shown in the figure. For recalibration of the fatal plus non-fatal CVD risk score, coefficients from the corresponding model in Table 1 and rates for total CVD events should be used.

Figure 3. Observed and predicted 10-year risk of fatal CVD event in risk score validation, by cohort and deciles of risk

Figure 4. Country risk charts for 10-year risk of fatal CVD

* To establish a person’s risk, first the column representing the person’s sex, smoking, and diabetes status should be found. Then the cell representing the person’s age, total cholesterol and systolic blood pressure levels should be located. Total (fatal or non-fatal) 10-year CVD risk would be higher than those seen in the figure by the ratio of total-to-fatal CVD event rates. For example, total risk for a person aged 60 years old and living in a high-income country, where about a third of all CVD events are fatal, would be three times higher. Total-to-fatal CVD ratio tends to go down with age, i.e. more fatal CVD events in older ages.^,– Total-to-fatal CVD ratio is likely lower in low- and middle-income countries where more CVD events are fatal due to lower healthcare and treatment access, and may be closer to 2. Risk charts are not shown for Czech Republic, Iran, and Malawi because their health examination surveys did not include older participants.

Figure 5. Distributions of 10-year risks of fatal CVD by country, sex, and age group.

Results for Czech Republic, Iran, and Malawi are shown only for 40-64 years of age because older individuals were not enrolled in the national health examination surveys.