CKD, Obesity and High Blood Pressure: Key Stroke Risk Factors Revealed

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Factors such as chronic kidney disease (CKD), obesity, high blood pressure, higher levels of “bad” cholesterol and smoking are closely connected to the risk of having a stroke, according to research published in Frontiers in Endocrinology.

Stroke affects more than 150,000 people each year and is considered the second most common cause of death worldwide. The number of strokes and subsequent stroke-related deaths rose by 70% and 43%, respectively, between 1990 and 2019 and is expected to increase to 4.90 million globally by 2030.

The burden of stroke is particularly high in low-income countries; among people with lower educational attainment; and for those who have other risk factors, including those with an increased body mass index (BMI) and waist circumference, current smokers, those with kidney disease and individuals with other cardiovascular risk factors. Previous research has shown chronic kidney disease significantly increases the risk of death in patients experiencing a stroke.

“Establishing a direct causal connection between a particular cause and its associated disease is difficult due to inherent limitations in observation-based studies, like potential confounding factors and skewed information,” wrote a team of investigators. “These hindrances make proving causality a tricky task.”

Investigators identified Mendelian randomization (MR) studies to assess the causal impact of certain factors on stroke risk. Eligible studies were chosen from databases including PubMed, Embase, Scopus and Web of Science from inception through August 2023. The reliability of the studies was determined using the Strengthening the Reporting of Observational Studies in Epidemiology incorporating MR (STROBE-MR) guidelines.

Among a possible 2,089 articles, 11 studies were ultimately chosen by two researchers for inclusion in the analysis.

Results revealed several risk factors for stroke, including chronic kidney disease, obesity, hypertension, low-density lipoprotein cholesterol (LDL-C) and smoking status. As such, investigators suggest smoking cessation as a primary intervention among individuals to lower their stroke risk.

As obesity elevates the likelihood of developing cardiovascular disease in general by inducing metabolic syndrome — a condition that involves elevated blood glucose levels and insulin resistance, impacts cholesterol profiles and is categorized by substantial body fat accumulation — reducing body weight among individuals at risk for overweight and obesity could markedly lower the risk of stroke. A subgroup analysis demonstrated that diastolic blood pressure and type 2 diabetes mellitus, both obesity-related indicators, were also risk factors for ischemic stroke, which further supports these findings.

Conversely, protective factors of stroke included high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) and education attainment. As higher educational levels were shown to decrease the risk of stroke among the general population, investigators encourage improving the overall education and cultural literacy levels of individuals.

Investigators mentioned limitations of the study including the finite number of MR studies evaluating stroke, which hindered their ability to ascertain publication bias. Further, they were unable to conduct subgroup analyses regarding age, sex and region and warned that the heterogeneity of the studies, although unsurprising, may warrant careful interpretation of the findings.

Despite the advantages of using MR methods compared with traditional meta-analysis, this type of methodology could be impacted by measurement errors in outcomes and exposure, coupled with a limited ability to fully understand longitudinal causal relationships.

“The likelihood of stroke can be significantly reduced by quitting smoking, maintaining a healthy body weight, addressing chronic kidney disease treatment and improving educational attainment, particularly in individuals predisposed to stroke, such as hereditary susceptibility,” investigators concluded.