Yiming Chen, Haryo Raden Himan, Yalkin Yazicioglu, Rachel Goh, Yip Han Chin, Bryan Chong, Srinithy Nagarajan, Martin Tze Wah Kueh, Jiong‐Wei Wang, Mark M Muthiah, Xin Zhou, Mark Y. Chan, Anurag Mehta, Mamas A Mamas, Muhammad Ali Zaib Khan, Nicholas WS Chew
Cardiovascular-kidney-liver-metabolic (CKLM) diseases constitute the presence of MASLD, T2D, CKD, obesity and/or CVD, that often co-exist and synergistically increase cardiovascular risk. However, the prevalence, extent and outcomes of the CKLM burden remain poorly understood. This population-based study utilised National Health and Nutrition Examination Survey (NHANES) 2007-2018 database, examining individuals’ number (0-4) and permutations of CKLM diseases, namely: type 2 diabetes (T2D), obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), chronic kidney disease (CKD). The primary outcome was all-cause mortality. Cox regression models were constructed to evaluate the relationship between CKLM phenotypes and all-cause mortality, adjusting for age, sex, race, socioeconomic status, and physical activity. The weighted cohort represented 97.8 million US adults (mean age 47.7±16.7 years). 54.16% of the cohort at ≥1 CKLM diseases. From 2007 to 2018, the proportion of individuals with ≥2 CKLM diseases increased from 32.4% to 55.6% of the population, with the largest increase in proportion of individuals with 4 diseases. The most common CKLM phenotype was MASLD-obesity (23.0%), followed by MASLD-obesity-T2D (5.1%). The highest mortality rates were observed in individuals with 4 CKLM diseases (21.4%), followed by 3 diseases (12.2%). Cox regression revealed that 4 diseases predicted the highest mortality risk (aHR 2.24, 95%CI: 1.66-3.02, p<0.001), followed by 3 diseases (aHR 1.52, 95%CI: 1.25-1.85, p<0.001). The MASLD-T2D-CKD phenotype (aHR 3.13, 95%CI: 1.80-5.42, p<0.001) and T2D-CKD phenotype (aHR 3.26, 95%CI: 2.33-4.55, p<0.001) predicted the highest mortality risk. The CKLM multimorbidity burden is rising in the US population. Higher CKLM burden (≥3 CKLM diseases) and CKD-centric phenotypes (MASLD-T2D-CKD or T2D-CKD) independently predict the highest mortality risk. Population estimates and prognostic outcomes of cardiovascular-kidney-liver-metabolic phenotypes and diseases in the US population. CKD, chronic kidney disease; CKLM, cardiovascular-kidney-liver-metabolic; MASLD, metabolic dysfunction-associated steatotic liver disease; T2D, Type 2 diabetes.