Dixon Yang, MD

Horn JW, Feng T, Mørkedal B, Strand LB, Horn J, Mukamal K, Janzsky I. Obesity and Risk for First Ischemic Stroke Depends on Metabolic Syndrome: The HUNT Study. Stroke. 2021;52:3555–3561.

Obesity is thought to be an important modifiable risk factor for ischemic stroke, especially given its high prevalence in certain European countries and the United States. However, obesity relationship to ischemic stroke may be more complex as there is still uncertainty on whether obesity itself or metabolic consequences of obesity are drivers of stroke risk. Horn et al. sought to assess the long-term association of weight, metabolic health, and ischemic stroke risk in the HUNT study (Trøndelag Health Study), a large prospective population-based cohort investigation based in Norway.

The present analysis included 35105 participants from HUNT who were free of stroke at baseline and had complete information on demographics, metabolic risk factors, and relevant covariates. Body weight categories were determined by standard body-mass index (BMI) thresholds (normal weight: 18.5 to <25 kg/m2, overweight: 25 to 29.9 kg/m2, obese: ≥30 kg/m2). The authors used a modified definition of metabolic syndrome from the International Diabetes Federation. Metabolically unhealthy was defined as the presence of increased waist circumference (WC) (≥102 cm in men, ≥88 cm in women) and 2 or more of the following: increased non-fasting triglycerides (≥1.7 mmol/L), decreased high-density lipoprotein (<1.03 mmol/L in men, <1.29 mmol/L in women), increased blood pressure (≥130/85 mmHg) or use of blood pressure medication, increased non-fasting glucose (≥11.1 mmol/L), or diabetes diagnosis. Outcomes were stroke diagnosis based on ICD codes in administrative hospital system data.

Of 35105 participants, 32% had normal weight, 45% were overweight, and 23% were obese. There were 23% metabolically unhealthy participants. During a median observation time of 11.9 years (400185 person-years), 1161 participants had an ischemic stroke. Metabolically healthy overweight and obese individuals had similar risk for stroke compared to those with healthy normal weight. Examining by BMI groups alone, irrespective of metabolic health, did not show differential risk of stroke. Further, long-term obesity (>3 decades) did not show increased risk of stroke as long as individuals were metabolically healthy. Conversely, metabolically unhealthy individuals in all BMI categories had trend towards increased risk of ischemic stroke when compared to metabolically healthy counterparts. This increased risk (30%) was greatest in metabolically unhealthy obese participants.

The authors concluded that obesity was not an independent risk factor for ischemic stroke; rather, metabolic consequences of obesity were more important for stroke risk. The study followed a large and stable population over many decades with virtually complete follow-up. There is limited generalizability to non-Norwegian participants. Non-fasting serum metabolic markers may pose accuracy issues, but sensitivity analysis adjusting for time since last meal showed similar results. There is no information on stroke subtype. Regardless, the results of the study importantly highlight the need to consider metabolic consequences of obesity and not just obesity itself in stroke risk reduction.