Background: Major cardiovascular diseases (CVD), including heart attack and stroke, are leading causes of premature mortality and disability in low- and middle-income countries (LMICs). Although key noncommunicable disease (NCD) risk factors are well established, their relative impact and variation across countries and health systems remain unclear.

Objectives: This dissertation assessed determinants of major CVD and the potential reduction in future burden achievable through risk factor modification.

Methods: We examined nationally representative WHO STEPS surveys from 42 countries between 2014 and 2022. Multilevel analysis assessed the combined impact of eight modifiable risk factors for CVD, controlling for various individual and country-level variables. Random-effects meta-analyses calculated pooled associations between these eight major NCD risk factors and CVD, accounting for socioeconomic influences. Subgroup and meta-regression analyses explored sources of heterogeneity. Pooled odds ratios were converted to relative risks using Zhang and Yu's (1998) correction, and potential impact fractions (PIFs) were applied to GBD 2023 estimates to project potentially avoidable deaths and disability-adjusted life years (DALYs) under plausible risk-factor-reduction scenarios.

Results: The pooled prevalence of major cardiovascular disease (CVD) was around 8%, with notable differences across countries. Multilevel analysis showed that older age groups had higher CVD risks: 30-44 years (AOR=1.35; 1.25-1.46), 45-59 years (AOR=1.92; 1.77-2.08), and 60-69 years (AOR=2.91; 2.67-3.18). Men had a 6% lower risk compared to women (AOR=0.94; 0.89-0.99). Among modifiable risk factors, hypertension (AOR=1.53; 1.45-1.62), diabetes (AOR=1.41; 1.32-1.51), inactive and sedentary lifestyle (AOR=1.21; 1.01-1.33), alcohol use (AOR=1.20; 1.12-1.28), obesity (AOR=1.17; 1.11-1.24), and smoking (AOR=1.10; 1.02-1.18) were linked to higher odds of developing CVD. Countries with high obesity rates (AOR=5.29; 2.34-11.94) and smoking prevalence (AOR=1.80; 1.26-2.58) showed increased CVD occurrence. Conversely, moderate air pollution exposure (AOR=0.47; 0.25-0.88) and low- to middle-income status (AOR=0.37; 0.25-0.55) and high-middle- and high-income status (AOR=0.51; 0.34-0.76) were associated with lower CVD risk compared to high-pollution and low-income nations. Meta-analysis confirmed the associations: hypertension (AOR=1.87; 1.45-2.42), diabetes (AOR=1.46; 1.30-1.65), smoking (AOR=1.52; 1.21-1.93), obesity (AOR=1.30; 1.20-1.41), and alcohol consumption (AOR=1.23; 1.07-1.41) significantly increased CVD risk, though heterogeneity between countries was high (I²=60-90%). Meta-regression revealed that a 10% rise in out-of-pocket health expenditure increased hypertension- and diabetes-related CVD risk by 5.5% and 7.3%, respectively, while each $1,000 increase in GNI per capita reduced hypertension-related risk by 2%. Across 34 countries with significant risk factor–CVD associations, a 10% relative risk-factor reduction could avert an estimated 55,000 deaths and over 1.7 million DALYs by 2035.

Conclusions: The impact of common NCD risk factors on CVD varies across countries, shaped by health systems and socioeconomic factors. Strengthening financial protection and managing chronic diseases are vital to reducing CVD and to sustainably controlling NCDs.