Cardio-kidney-metabolic (CKM) syndrome is defined by the American Heart Association as the intersection between metabolic, renal and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality and recent trends in the US is essential for developing targeted public interventions. We collected state-level and county-level CKM-associated age-adjusted premature cardiovascular mortality (aaCVM) (2010–2019) rates from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER). We linked the county-level aaCVM with a multi-component social deprivation metric: the Social Deprivation Index (SDI: range 0–100) and grouped them as follows: I: 0–25, II: 26–50, III: 51–75, and IV: 76–100. We conducted pair-wise comparison of aaCVM between SDI groups with the multiplicity adjusted Wilcoxon test; we compared aaCVM in men versus women, metropolitan versus nonmetropolitan counties, and non-hispanic white versus non-hispanic black residents. In 3101 analyzed counties in the US, the median CKM associated aaCVM was 61 [interquartile range (IQR): 45, 82]/100 000. Mississippi (99/100 000) and Minnesota (33/100 000) had the highest and lowest values respectively. CKM associated aaMR increased across SDI groups [I – 45 (IQR: 36, 55)/100 000, II- 61 (IQR: 49, 77)/100 000, III- 77 (IQR: 61, 94)/100 000, IV- 89 (IQR: 70, 110)/100 000; all pair-wise p-values < 0.001]. Men had higher rates [85 (64, 91)/100 000] than women [41 (28, 58)/100 000](p-value < 0.001), metropolitan counties [54 (40, 72)/100 000] had lower rates than non-metropolitan counties [66 (49, 90)/100 000](p-value < 0.001), and non-Hispanic Black [110 (86, 137)/100 000] had higher aaMR than non-Hispanic White residents [59 (44, 78)/100 000](p-value < 0.001). In the US, CKM mortality remains high and disproportionately occurs in more socially deprived counties and non-metropolitan counties. Our inability to reduce CKM mortality rates over the study period highlights the need for targeted policy interventions to curb the ongoing high burden.
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