Abstract
BACKGROUND: Mortality from familial hypercholesterolemia (FH) remains high due to late diagnosis, and the rate of timely diagnosis remains low (< 10% globally and < 1% in China). Early screening and treatment could significantly reduce mortality risk, especially among young adults. This study aims to evaluate the cost-effectiveness of universal genetic screening of young adults aged 18-40 years compared to universal cholesterol screening or current passive screening strategies (opportunistic cholesterol screening and genetic cascade testing) for FH in China. METHODS: A decision-analytic Markov model was constructed to simulate the lifetime (until 100 years old or 99% of patients died) coronary heart disease (CHD) events, discounted costs, gains in quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) of different screening strategies. The model targeted the general population aged 18-40 years (226,869,800 males and 209,030,180 females) from a healthcare provider's perspective. Model parameters were derived from published literatures and the largest nationwide screening program of FH in China. The willingness-to-pay threshold (US$38,042) was chosen as three times the Chinese per-capita gross domestic product (GDP) in 2023. Sensitivity analyses and threshold analyses were conducted to assess the robustness of the results. RESULTS: Universal genetic screening of young adults aged 18-40 years is cost-effective when compared to both current passive screening strategies and universal cholesterol screening. Compared with current passive screening, universal genetic screening could prevent 172,956 CHD events (88,766 non-fatal, 84,191 fatal) with additional costs of US$40.45 billion and gaining additional 1.23 million QALYs, corresponding to an ICER of US$32,960/QALY gained. Implementing universal genetic screening at younger ages would reduce the ICER from US$36,901/QALY to US$28,910/QALY. The model was most sensitive to the cost and sensitivity of genetic testing. If the cost of genetic testing decreased from US$96.50 to US$38.83 or $2.76, universal genetic screening would become very cost-effective or even cost-saving. CONCLUSIONS: Universal FH genetic screening in young adults has the potential to be cost-effective in China, compared to current passive screening strategy and universal cholesterol screening strategy. Performing screening in younger age would result in better cost-effectiveness benefit.