Progression to stage 4 cardiovascular-kidney-metabolic syndrome

1. Life’s Essential 8–based cardiovascular health index is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans (Baseline CKM stage 2 or 3; ideal versus poor index scores) (45% lower hazard; HR 0.55, 95% CI 0.40–0.75).

   “Higher LE8 index scores were strongly associated with lower risk; participants with ideal scores had a 45% lower hazard compared with those with poor scores”

   HumansBaseline CKM stage 2 or 3; ideal versus poor index scoresn = 2,493

   Lifestyle factors and progression from stage 2/3 to stage 4 cardiovascular-kidney-metabolic (CKM) syndrome in older adults: a cohort study

   Research Square·Oct 28, 2026Preprint

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1. Smoking is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans (Baseline CKM stage 2 or 3).

   “Heavy smoking (≥35 pack-years) was associated with higher risk”

   HumansBaseline CKM stage 2 or 3≥35 pack-yearsn = 2,493

   Lifestyle factors and progression from stage 2/3 to stage 4 cardiovascular-kidney-metabolic (CKM) syndrome in older adults: a cohort study

   Research Square·Oct 28, 2026Preprint

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1. Physical activity is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans (Baseline CKM stage 2 or 3; compared with no activity) (HR 0.71, 95% CI 0.58–0.89).

   “Compared with no activity, low- and moderate-intensity activity were associated with reduced hazards”

   HumansBaseline CKM stage 2 or 3; compared with no activitylow intensityn = 2,493

   Lifestyle factors and progression from stage 2/3 to stage 4 cardiovascular-kidney-metabolic (CKM) syndrome in older adults: a cohort study

   Research Square·Oct 28, 2026Preprint

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1. Spliceosome CHIP is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans (CKM stages 0–3 at baseline) (Adjusted HR 1.50, 95% CI 1.25–1.80; P<0.001).

   “spliceosome CHIP (aHR, 1.50; 95% CI, 1.25-1.80; P<0.001)”

   HumansCKM stages 0–3 at baselineMedian follow-up of 13.6 years

   Blood mutations linked to heart, kidney, and metabolic disease

   ESC Congress 2026 abstract·Oct 26, 2026

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1. TET2 CHIP is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans (CKM stages 0–3 at baseline) (Adjusted HR 1.18, 95% CI 1.08–1.30; P<0.001).

   “including TET2 (aHR, 1.18; 95% CI, 1.08-1.30; P<0.001)”

   HumansCKM stages 0–3 at baselineMedian follow-up of 13.6 years

   Blood mutations linked to heart, kidney, and metabolic disease

   ESC Congress 2026 abstract·Oct 26, 2026

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1. Non-DNMT3A CHIP is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans (CKM stages 0–3 at baseline) (Adjusted HR 1.20, 95% CI 1.13–1.28; P<0.001).

   “again driven by associations with non-DNMT3A CHIP subtypes (aHR; 1.20; 95% CI, 1.13-1.28; P<0.001)”

   HumansCKM stages 0–3 at baselineMedian follow-up of 13.6 years

   Blood mutations linked to heart, kidney, and metabolic disease

   ESC Congress 2026 abstract·Oct 26, 2026

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1. Clonal hematopoiesis of indeterminate potential is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans (CKM stages 0–3 at baseline) (Adjusted HR 1.11, 95% CI 1.07–1.15; P<0.001).

   “CHIP was independently associated with progression to stage 4 CKM syndrome (adjusted hazard ratio [aHR] 1.11; 95% CI, 1.07-1.15; P<0.001;”

   HumansCKM stages 0–3 at baselineMedian follow-up of 13.6 years

   Blood mutations linked to heart, kidney, and metabolic disease

   ESC Congress 2026 abstract·Oct 26, 2026

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1. Discharge estimated plasma volume status is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans.

   “For dischargeePVS, a significant risk signal emerged starting from Q2.”

   HumansHospitalized patients with stage 2 cardiovascular-kidney-metabolic syndrome; discharge ePVS starting from Q210 yearsn = 36,505

   Blood fluid measure linked to worsening heart-kidney-metabolic disease

   Frontiers in endocrinology·Oct 15, 2026

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1. Admission estimated plasma volume status is associated with progression to stage 4 cardiovascular-kidney-metabolic syndrome in humans (43% higher risk versus Q1).

   “The highest admission ePVSquartile was associated with 43%, 88%, and 76% higher risks of CKM4, CKM4b, andheart failure versus Q1.”

   HumansHospitalized patients with stage 2 cardiovascular-kidney-metabolic syndrome; highest admission ePVS quartile versus Q110 yearsn = 36,505

   Blood fluid measure linked to worsening heart-kidney-metabolic disease

   Frontiers in endocrinology·Oct 15, 2026

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