Quantifying the contributions of cardiovascular risk factors to cardiovascular disease trends in 21st century Japan: a microsimulation study

Abstract

Background: Recent stagnation or worsening trends in cardiovascular disease (CVD) risk factors, including low-density lipoprotein cholesterol (LDL-c) and obesity, might slow the decline in Japan's CVD burden. We aimed to quantify the impact of national changes in CVD risk factor distributions on Japan's CVD burden from 2001 to 2019.

Methods: We conducted a microsimulation study with counterfactual analysis using IMPACT_NCD-JPN, a validated model based on real-world data. It simulated a synthetic Japanese population (ages 30-99) from 2001 to 2019 using life-course data on seven CVD risk factors, estimating CVD incidence, mortality, and healthcare economics for synthetic individuals. The base-case reflected observed trends; counterfactual scenarios assumed 2001 levels persisted. Primary outcome was national CVD incidence (stroke and coronary heart disease).

Findings: From 2001 to 2019, systolic blood pressure (SBP) and smoking declined markedly (men/women) by 6·8/7·2 mmHg and 18·4/6·8%, respectively, while LDL-c, HbA1c, body mass index (BMI), physical activity (PA), and fruit/vegetable (FV) consumption showed smaller or adverse trends. Under the base-case and counterfactual scenarios, IMPACT_NCD-JPN estimated CVD incidence and quantified the differences between the scenarios. The changes in the CVD risk factors prevented or postponed 840,000 (95% uncertainty interval: 540,000-1,300,000) national CVD cases, cumulative from 2001 to 2019. Individual contributions were: SBP 540,000; smoking 280,000; LDL-c 27,000; HbA1c 7900; BMI -15,000; PA -16,000; and FV consumption -11,000.

Interpretation: SBP and smoking reductions drove most CVD burden declines in Japan (2001-2019). Modest benefits came from LDL-c and HbA1c, while rising BMI, and low PA and FV intake partly offset these benefits.

Funding: JSPS KAKENHIJP22K17821, JP25K02863; the Ministry of Health, Labour and Welfare Comprehensive Research on Life-Style Related 22FA1015, 24FA1015.

Keywords: All-cause deaths; Cardiovascular risk factors; Coronary heart disease; Indirect costs; Japan; Medical costs; Microsimulation study; Public health; Quality-adjusted life years; Stroke; The national burdens of cardiovascular disease.

Fig. 1

Overview of study design, including counterfactual analysis and IMPACT_NCD-JPN structure. Abbreviations: CVD, cardiovascular diseases; GAMLSS, Generalised Additive Models for Location, Scale, and Shape; CHD, coronary heart disease; QALYs, quality-adjusted life years; CPPs, cases prevented or postponed; CYPPs, case-years prevented or postponed; DPPs, deaths prevented or postponed; SBP, systolic blood pressure; LDL-c, low density lipoprotein cholesterol; BMI, body mass index; PA, physical activity; FV, fruits and vegetables. ¹Cigarette consumption for current smokers. ²Detailed age- and sex-stratified distributions are presented in Supplementary Figure S1 in Supplementary Results. IMPACT_NCD-JPN simulated synthetic individuals with specific age (1-year), sex, year (1-year), and values for seven CVD risk factors: SBP, smoking status, LDL-c, HbA1c, BMI, PA, and FV consumption. Each CVD risk factor was modelled based on age, sex, year, and, where applicable, selected relevant CVD risk factors among the seven. A brief structure of IMPACT_NCD-JPN is also presented in the Technical Appendix “Introduction” in Supplementary Methods.

Fig. 2

Annual incidence of CHD and stroke, and their cumulative CPPs from 2001 to 2019 in Japan, under the base-case scenario and counterfactual scenarios where each modelled CVD risk factor, and all combined, are fixed at 2001 levels. Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease; PA, physical activity; FV, fruit and vegetable consumption; BMI, body mass index; LDL-c, low-density lipoprotein cholesterol; SBP, systolic blood pressure; CPPs, cases prevented or postponed. ¹SBP, LDL-c, and HbA1c were adjusted for medication use of antihypertensive, cholesterol-lowering, and diabetes treatments, respectively.

Fig. 3

Cumulative CYPPs for CHD and stroke, DPPs, net gained QALYs, net saved direct and indirect costs for CHD and stroke from 2001 to 2019 in Japan, assessed by comparing counterfactual scenarios where each modelled CVD risk factor, and all combined, are fixed at 2001 levels with the base-case scenario. Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease; PA, physical activity; FV, fruit and vegetable consumption; BMI, body mass index; LDL-c, low-density lipoprotein cholesterol; SBP, systolic blood pressure; CYPPs, case-years prevented or postponed; DPPs, deaths prevented or postponed. Results are summarised using medians (points) and 95% uncertainty intervals (error bars). Since the scenarios share common parameters, the results are correlated; therefore, overlapping UIs do not necessarily indicate a lack of statistical significance. For details, please refer to Technical Appendix “Model outputs” in Supplementary Methods. ¹SBP, LDL-c, and HbA1c were adjusted for medication use of antihypertensive, cholesterol-lowering, and diabetes treatments, respectively.