Study: Metabolic Syndrome Increases Cardiovascular, Mortality Risk in Patients With CKD

Patients with chronic kidney disease who also have metabolic syndrome are at a higher risk of death and cardiovascular events, according to a new prospective study of more than 5,000 patients.

The report was published in the Journal of Internal Medicine and based on a follow-up of 6.5 years. Corresponding author Florian Kronenberg, MD, of the Medical University of Innsbruck, in Austria, and colleagues, wrote that until now, limited data were available about the risks associated with metabolic syndrome in patients who had chronic kidney disease and moderately reduced estimated glomerular filtration rate (eGFR) and/or albuminuria.

The investigators used a cohort of 5110 patients with chronic kidney disease from the German Chronic Kidney Disease study. Of those, 3284 (64.3%) had a metabolic syndrome at baseline.

After data adjustment, the investigators found patients with a metabolic syndrome had higher risks of all-cause mortality (HR = 1.26; 95% CI, 1.04–1.54) and cardiovascular events (HR = 1.48; 95% CI, 1.22–1.79).

Yet, the authors found that risk increase was linked in part with the number of components of metabolic syndrome a particular patient had. Those components included increased weight circumference, glucose, triglycerides, hypertension, and decreased HDL cholesterol. The more components a patient had, the higher the risk. In fact, the investigators said each component carried a hazard ratio of 1.09 for mortality and 1.23 for cardiovascular events, which translated to hazard ratios between 1.50 and 2.50 for patients who had 4 of the 5 metabolic syndrome components.

Of the 5 components, glucose was linked with the highest hazard ratios, followed by HDL cholesterol and triglycerides.

Kronenberg and colleagues said while the findings may have aligned with predictions, studies evaluating metabolic syndrome in patients with chronic kidney disease are “surprisingly sparse,” likely because most definitions of metabolic syndrome require blood samples taken during a fasting state, something that can make it difficult to recruit patients.

It is not clear why patients with metabolic syndrome appear to have higher risk, though the investigators offered some potential causes.

“They might include misguided immune system activity, dysregulation of haemostasis, and excess intra-abdominal fat,” they wrote.

For physicians treating patients with metabolic syndrome, Kronenberg and colleagues said these new data offer the possibility of a new approach. Traditionally, they said, metabolic syndrome is treated as a binary, “yes” or “no” diagnosis. This makes communication clear-cut, but the investigators said it may not be reflective of the complexity of the factors at play.

For instance, the fact that the number of metabolic syndrome components appears to correlate with risk could empower patients.

“This could be a motivating factor for the individual patient in the sense that each metabolic syndrome component successfully avoided might decrease the risk for a cardiovascular endpoint or premature death,” they said. “Hence not all metabolic syndromes are created equally and individual analysis of each of the metabolic syndrome components should guide the search to find the most promising target for therapeutic intervention on a case by case basis.”

The authors said targeting the glucose component is likely to have the highest impact. They said lifestyle changes and drug treatment could also lead to meaningful impacts on other components, and ultimately, lower risk.

Reference

Pammer LM, Lamina C, Schultheiss UT, et al. Association of the metabolic syndrome with mortality and major adverse cardiac events: A large chronic kidney disease cohort. J Intern Med. Published online August 3, 2021. doi:10.1111/joim.13355