The burden of premature mortality from cardiovascular diseases: A systematic review of years of life lost

**Background:** Cardiovascular disease (CVD) remains the leading cause of premature mortality globally, accounting for about one-third of all deaths. Years of life lost (YLL) is a standard metric that quantifies premature mortality by accounting for both the number of deaths and the age at which they occur. Two main methods are used: years of potential life lost (YPLL), which uses an arbitrary upper age cut-off, and standard expected years of life lost (SEYLL), which compares age of death to standard life expectancy. This systematic review aimed to identify studies on premature CVD mortality and synthesize their YLL findings by region, CVD type, sex, and study time.

**Methods:** A systematic review was conducted following PRISMA guidelines, with a registered protocol (PROSPERO CRD42021288415). Five electronic databases (PubMed, Scopus, Web of Science, CENTRAL) were searched from inception through October 18, 2022, supplemented by reference list checking and Google Scholar. Eligible studies were observational, reported premature CVD mortality using YLL (YPLL or SEYLL methods), and were written in English. Reviews, meta-analyses, letters, comments, and editorials were excluded. Two authors independently screened and extracted data. The Newcastle-Ottawa Scale (NOS) was used for quality assessment. Due to the absence of reported measures of uncertainty (95% CI or standard error) in most studies, descriptive analysis (median and IQR) was used instead of meta-analysis.

**Key Results:** From 2012 identified records, 40 studies met inclusion criteria. Quality assessment yielded 37 studies of good quality and 3 of satisfactory quality. Seventeen studies used the YPLL method (Gardner/Romeder) and 23 used the SEYLL method (GBD). Studies represented all WHO regions except the Eastern Mediterranean. The overall median YPLL rate was 594.2 per 100,000 (IQR: 163.4–992.8), and the median SEYLL rate was 1357.0 per 100,000 (IQR: 723.7–2518.4). The highest YPLL rates were in South-East Asia (1205 per 100,000), the Americas (1163 per 100,000), and Africa (1140 per 100,000). The lowest YPLL rates were in Switzerland and Belgium. For SEYLL, Serbia had the highest rate and South Korea the lowest. Over the past three decades (1990–2022), the YPLL and SEYLL rates for overall CVD increased slightly, while the SEYLL rate for cerebrovascular disease declined slightly. The SEYLL rate increased notably in the Western Pacific region, declined in Europe, and plateaued in the Americas. Males had higher median YLL rates than females (YPLL: 753.8 vs. 160.3 per 100,000; SEYLL: 1558.2 vs. 1170.2 per 100,000), and the male rate increased substantially over three decades.

**Clinical Implications:** This review confirms that premature CVD mortality remains a substantial burden, particularly in middle-income countries and among men. The findings suggest that the United Nations Sustainable Development Goal target 3.4 (25% reduction in premature NCD mortality by 2025) will be challenging to achieve, especially for low- and middle-income countries. The increasing burden among men and in LMICs underscores the need for cost-effective prevention strategies, including control of diabetes, obesity, high cholesterol, and behavioral risk factors (tobacco, alcohol, sodium intake). Continuous monitoring using YLL methods is essential for tracking progress and guiding resource allocation.