Combined Cardiometabolic Biomarker Burden Tracks CKM Progression

Adults who carry several elevated cardiometabolic markers at once face a stepwise higher risk of developing a first cardiovascular, kidney, or metabolic disease and of going on to accumulate a second and third, according to a prospective cohort study scheduled for presentation at American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado. Several of the markers come from measurements pharmacists already see, including blood pressure, lipids, and body size, which may help flag patients early in the cardiovascular-kidney-metabolic (CKM) continuum.¹

Investigators from Third Xiangya Hospital of Central South University in Changsha, China, analyzed 262,464 UK Biobank participants who had no cardiovascular disease, type 2 diabetes (T2D), or chronic kidney disease (CKD) at baseline.¹

Five Markers, Three Transitions

The team evaluated 49 candidate biomarkers across 5 domains (inflammation, insulin resistance, dyslipidemia, adiposity, and blood pressure), using time-dependent area under the curve and concordance index to choose representative markers. Five were selected: the C-reactive protein-to-albumin ratio, the metabolic score for insulin resistance (METS-IR), the triglyceride-to-high-density lipoprotein (HDL) cholesterol ratio, the waist-to-height ratio, and systolic blood pressure.¹

Multistate models then estimated how individual markers, the number of elevated markers, and a weighted 5-Item Cardiometabolic Risk Score (5-CMRS) were associated with 3 sequential transitions: from baseline to a first cardio-renal-metabolic disease (FCRMD), from FCRMD to double cardio-renal-metabolic disease (CRMD), and from double to triple CRMD. Over a median follow-up of 15.62 years, 44,339 participants developed FCRMD, 7218 progressed to double CRMD, and 721 progressed to triple CRMD.¹

Graded Risk, Strongest at the First Step

A higher count of elevated markers showed graded associations across all 3 transitions. Compared with the lowest 5-CMRS category, the highest category was associated with hazard ratios of 2.80 for the first transition, 1.84 for the second, and 1.71 for the third. Associations were strongest for incident T2D in disease-specific analyses. METS-IR contributed the largest share across transitions, and additive interactions between markers were observed mainly during early progression.¹

The abstract does not report confidence intervals or covariate adjustment, and as an observational analysis, it cannot show that lowering these markers changes a patient's trajectory.¹

The work builds on the American Heart Association (AHA) presidential advisory that defined CKM health as the interplay among metabolic risk factors, CKD, and the cardiovascular system and called for a staging approach that promotes prevention across the life course.²

Reading the Signals Together

The study's focus on combined burden echoes guidance experts have shared with Pharmacy Times. In a previous interview, Andrew Bzowyckyj, PharmD, BCPS, CDCES, FADCES, FAPhA, FCCP, senior scientific director and learning consultant at the National Kidney Foundation, said looking at CKM signals together sharpens risk stratification and moves care beyond a hemoglobin A1C-focused model.³

"We really shouldn't be looking at 1 or 2 in isolation. We want to look at all of them, or whatever might be available, and that really helps with risk stratification," Bzowyckyj said.³

He also described inflammation, one of the domains captured in the new score, as a counseling opportunity, noting that glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, colchicine, and metformin have anti-inflammatory effects. "You might describe systemic inflammation as the slow burn that comes with these CKM conditions," he said.³

Staging Patients Before a First Diagnosis

The highest hazard ratio in the study appeared at the first transition, before participants had any of the 3 conditions. Wendy L. St. Peter, PharmD, FCCP, FASN, FNKF, professor emerita at the University of Minnesota College of Pharmacy and a writing committee member for the AHA and American College of Cardiology CKM syndrome guideline, previously told Pharmacy Times that pharmacists can pair the AHA PREVENT calculator, which incorporates estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), with the Kidney Disease: Improving Global Outcomes heat map to stage patients.⁴

Once a patient's CKM stage is determined, St. Peter said, “The guideline helps pharmacists decide which evidence-based therapies should be considered."⁴

REFERENCES

1. Peng J, Li X, Li A, Yi B, Huang Z. Cardiometabolic risk factors and the trajectory of cardiovascular-kidney-metabolic multimorbidity: a prospective cohort study. Abstract FR-OR025. Presented at: American Society of Nephrology Kidney Week 2026; October 23, 2026.

2. Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association. Circulation. 2023;148(20):1606-1635. doi:10.1161/CIR.0000000000001184

3. Bzowyckyj A, Halpern L. Reading CKM signals together: a pharmacist's guide. Pharmacy Times. August 27, 2026. Accessed October 21, 2026. https://www.pharmacytimes.com/view/reading-ckm-signals-together-a-pharmacist-s-guide

4. St Peter WL, Halpern L. New CKM guideline elevates pharmacists' role in comprehensive medication management. Pharmacy Times. July 7, 2026. Accessed October 21, 2026. https://www.pharmacytimes.com/view/new-ckm-guideline-elevates-pharmacists-role-in-comprehensive-medication-management