People with clogged arteries who carry signs of persistent inflammation face a sharply higher chance of heart attack, stroke, or death, and they also run up much larger medical bills, according to one of the largest real-world analyses of its kind. The study, published in Cardiology and Therapy, followed nearly 75,000 American adults with established atherosclerotic cardiovascular disease drawn from a national database of insurance claims linked to laboratory results. Researchers found that patients whose blood tests showed sustained systemic inflammation had a 24 percent higher risk of a composite endpoint of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality than similar patients without that inflammatory signal. For those who also had moderate to severe chronic kidney disease, the risk climbed even further, reaching 62 percent above the baseline group.
The analysis was designed to fill a persistent gap. Inflammation has been recognized for two decades as a driver of atherosclerosis, and large clinical trials have shown that lowering inflammation reduces cardiovascular events. Yet patients with chronic kidney disease are rarely included in those trials, and real-world data on the economic toll of inflammation in this population have been scarce. The new study examined both questions at once, tracking cardiovascular outcomes alongside healthcare costs and resource use in patients with and without kidney disease.
The research team used the Komodo Healthcare Map, a database of deidentified administrative medical and pharmacy claims linked with laboratory measurements for a nationally representative US population. Because the data were deidentified, the study was exempt from institutional review board approval and was conducted in accordance with the Declaration of Helsinki, following the STROBE guidelines for observational cohort studies. The retrospective design means the findings describe associations, not causal effects, a distinction the authors emphasize throughout their report.
To build the study population, the researchers started with more than 11.2 million adults who had evidence of established atherosclerotic cardiovascular disease between July 1, 2016, and September 30, 2023. Patients qualified if they had at least one inpatient claim or two outpatient claims for myocardial infarction, ischemic stroke, or peripheral artery disease, or a procedure code for coronary revascularization. From that pool, roughly 1.07 million had high-sensitivity C-reactive protein testing, and 91,164 had at least one eligible result in the year before or after their first cardiovascular diagnosis. After applying additional criteria, 74,884 patients remained for analysis.
High-sensitivity C-reactive protein served as the marker of systemic inflammation. Patients with at least one value between 2 and 10 milligrams per liter were classified as having inflammation, while those with all values below 2 milligrams per liter were classified as not having it. Tests performed within 30 days of a hospital or emergency department visit involving antimicrobials, antivirals, antifungals, or corticosteroids, or values above 10 milligrams per liter, were excluded to avoid counting acute infections or other transient inflammatory episodes. This cutoff approach follows prior cardiovascular research showing that a single elevated reading predicts future events. Chronic kidney disease stage 3 or 4 was identified through medical claims or laboratory-reported estimated glomerular filtration rate, with creatinine values converted using the 2021 CKD-EPI equation when eGFR results were unavailable. Patients on dialysis were excluded, as were those with infectious diseases, acute kidney injury, cancer other than skin cancer, severe hepatic disease, or transplants.
The final cohort had a mean age of 60.5 years, and 61.7 percent were of White race. Nearly half, 49.2 percent, showed systemic inflammation, while 8.5 percent had chronic kidney disease stage 3 or 4, most of them at stage 3. Patients with inflammation carried a heavier comorbidity burden, with higher rates of obesity, hypertension, type 2 diabetes, smoking, heart failure, and autoimmune disease. Those with kidney disease were roughly a decade older than patients without it. The authors note that patients who received hsCRP testing tended to be younger and more often commercially insured than those who were not tested, a representativeness limitation they addressed by comparing the two groups in supplemental analyses.
During a median follow-up of 30 months, the inflammatory signal translated into measurably worse outcomes. Incidence rates of the composite endpoint ran 17.29 per 1,000 person-years among patients with inflammation versus 13.49 among those without, and 43.55 versus 35.67 among patients who also had stage 3 or 4 kidney disease. After adjusting for age, sex, race and ethnicity, region, insurance type, comorbid conditions, comorbidity index, and medication use, systemic inflammation alone carried a hazard ratio of 1.24 for the composite endpoint. Kidney disease stage 3 or 4 alone carried a hazard ratio of 1.33. Having both raised the hazard ratio to 1.62. The individual components followed a similar pattern, though the risk of nonfatal myocardial infarction was not elevated in patients with kidney disease alone.
The economic findings were equally striking. Total all-cause healthcare costs averaged $18,002 per patient per year among patients with inflammation and no kidney disease, compared with $15,070 for those without inflammation, a difference of $2,932. Among patients with stage 3 or 4 kidney disease, costs reached $26,089 per patient per year with inflammation versus $20,753 without, a gap of $5,336. After adjusting for patient characteristics and baseline costs, inflammation alone was associated with a 14 percent increase in total costs, kidney disease alone with an 11 percent increase, and the combination with a 30 percent increase. Inpatient and outpatient services together accounted for roughly 70 percent of total spending. Healthcare resource use rose in parallel, with higher rates of inpatient admission, outpatient visits, emergency department visits, and pharmacy fills across the inflamed groups.
The results align with a growing body of evidence. A retrospective Swedish cohort found that patients with C-reactive protein at or above 2 milligrams per liter had a 30 percent higher risk of major adverse cardiovascular events than those below that threshold. In the CANTOS trial, participants whose on-treatment hsCRP fell below 2 milligrams per liter experienced a 25 percent reduction in such events, and a post hoc analysis showed canakinumab reduced events by 18 percent in patients with kidney disease versus 14 percent in those without, with greater absolute benefit given their higher baseline risk. Low-dose colchicine, currently the only approved medication targeting cardiovascular inflammation, has also been shown to reduce events, though its use may be limited by safety concerns in patients with kidney disease and by the neutral results of the CLEAR SYNERGY trial. Randomized trials of monoclonal antibodies targeting interleukin-6, including ziltivekimab and related agents, are now being evaluated specifically in patients with atherosclerotic disease and kidney impairment.
The authors caution that their findings are observational and subject to residual confounding, since factors such as socioeconomic status, treatment intensity, and adherence were not fully captured. Costs were imputed from Medicare fee-for-service benchmarks rather than directly observed, and a single hsCRP measurement may not reflect how inflammation changes over time. Cause of death could not be determined, so all-cause mortality was used in the composite endpoint, meaning the association may reflect broader illness burden as well as cardiovascular risk. Still, the study represents the largest analysis to date of inflammation, cardiovascular events, and economic burden in US patients with atherosclerotic disease, including more than 6,000 patients with stage 3 or 4 kidney disease, a group rarely represented in clinical trials. The authors conclude that inflammation should be assessed in the care of these patients and that reducing it remains an unmet need, particularly for those whose inflammation persists despite optimized traditional risk factors and for those with advanced kidney disease.
Subject of Research: Association between systemic inflammation, cardiovascular events, and healthcare costs in patients with atherosclerotic cardiovascular disease and chronic kidney disease
Article Title: Real-World Analysis of the Association Between Systemic Inflammation, Cardiovascular Events, and Economic Burden Among Patients with Atherosclerotic Cardiovascular Disease and Chronic Kidney Disease
Article References: Nguyen, C., Ryali, R., Skaar, J. R., Chow, W., Robar, C., Kaufman, A., Li, W., & Shah, B. (2026). Real-World Analysis of the Association Between Systemic Inflammation, Cardiovascular Events, and Economic Burden Among Patients with Atherosclerotic Cardiovascular Disease and Chronic Kidney Disease. Cardiology and Therapy, 15(3), 319-338. https://doi.org/10.1007/s40119-026-00459-3
Image Credits: AI Generated
DOI: 10.1007/s40119-026-00459-3
Keywords: systemic inflammation, atherosclerotic cardiovascular disease, chronic kidney disease, hsCRP, major adverse cardiovascular events, healthcare costs, healthcare resource utilization, retrospective cohort study, Komodo Healthcare Map, C-reactive protein, cardiovascular risk, real-world evidence
News Source: Frances Kline. (November 4, 2026). Inflammation Raises Heart Attack, Stroke, Death Risk and Costs in Heart Disease Patients. Scienmag.
