Increasing body mass index (BMI) was linked to lower thromboembolic and mortality risks, according to findings published in Clinical Cardiology. The paradoxical findings, however, were driven by evidence found in randomized studies, and some observational studies included in analysis showed conflicting results.

The World Health Organization (WHO) definition of obesity is a BMI of ≥30 kg/m2. Obesity is associated with new-onset atrial fibrillation (AF), and for paroxysmal AF progressing to permanent AF, perhaps due to synergistic effects of other obesity-related risk factors for AF such as diabetes mellitus, heart failure with preserved ejection fraction, hypertension, left atrial enlargement, and obstructive sleep apnea.

Similarly, being underweight, defined as a BMI of <18.5 kg/m2, has also been associated with the development of AF, as well as the recurrence of AF postablation. This suggests a possible U-shaped relationship between incident AF and BMI, according to researchers. Researchers indicated that a controversial idea known as the “obesity paradox” has been seen in studies that show a protective effect of obesity on AF-related outcomes, despite its association with mortality, other cardiovascular diseases, and stroke risk factors such as diabetes mellitus, hypertension, and metabolic syndrome.

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To explore this obesity paradox, investigators conducted a systematic review and meta-analysis of the literature regarding the impact of underweight, overweight (defined as BMI 25 to <30 kg/m2), obesity, and morbid obesity (defined as BMI ≥40 kg/m2) compared with normal BMI on AF‐related outcomes in anticoagulated patients with AF. Of the 6553 articles identified by searching Embase and Medline, 37 articles were selected for the systematic review, 9 of which were included in the meta-analysis (4 Phase III randomized controlled trials, 5 observational studies).

Investigators found that, compared with anticoagulated patients with AF and “normal” BMI, anticoagulated patients with AF and overweight, obesity, and morbid obesity showed significantly lower risks for stroke or systemic embolism (risk ratio [RR], 0.80; 95% CI, 0.73-0.87; P <.001; RR, 0.63; 95% CI, 0.57-0.70; P <.001; and RR, 0.42; 95% CI, 0.31-0.57; P <.001; respectively) as well as significantly lower all-cause mortality (RR, 0.73; 95% CI, 0.64-0.83; P <.001; RR, 0.61; 95% CI, 0.52-0.71; P <.001; and RR, 0.56; 95% CI, 0.47-0.66; P <.001; respectively).

In contrast, the risk for stroke or systemic embolism was significantly higher in anticoagulated patients with AF and underweight (RR, 1.92; 95% CI, 1.28-2.90; P =.002) as was the risk for all-cause mortality (RR, 3.57; 95% CI, 2.50-5.11; P <.001).

Compared with the risks seen in patients with normal BMIs, the risks of developing major bleeding in anticoagulated patients with AF and overweight and obesity were also significantly lower (RR, 0.86; 95% CI, 0.76-0.99; P =.03; and RR, 0.88; 95% CI, 0.79-0.98; P =.02; respectively) as were intracranial bleeding risks (RR, 0.75; 95% CI, 0.58-0.97; P =.03; and RR, 0.57; 95% CI, 0.40-0.80; P =.001; respectively).

Similar risks for major and intercranial bleeding were observed in underweight (RR, 1.37; 95% CI, 0.65-2.88; P =.41; and RR, 0.45; 95% CI, 0.11-1.84; P =.27, respectively) and morbidly obese anticoagulated AF patients (RR, 0.73; 95% C, 0.38-1.42; P =.36; no data on risk for intracranial bleeding).

Although most results included in this analysis support the obesity paradox, investigators pointed out that several observational studies showed AF and obesity associated with a similar risk for stroke, SE, myocardial infarction, and venous thromboembolism compared with AF and normal BMI, and that in two observational studies, no significant differences in risk for ischemic stroke, systemic embolism, stroke, or myocardial infarction could be seen between AF and underweight and AF and normal BMI, while two studies demonstrated worse outcomes.

Limitations included that the studies did not all agree upon how to categorize patients according to BMI tertiles or quartiles, and many studies only measuring patient’s weight at baseline, with no adjustments made for changes occurring during follow-up, although one study that did so noted only small changes in weight. Four of the studies had to be excluded due to patients not being anticoagulated, and those that were included did not agree on novel oral anticoagulants dosage.

Study investigators concluded that this meta-analysis of, “the controversial ‘obesity paradox’ demonstrated lower thromboembolic and mortality risks with increasing BMI in anticoagulated AF patients. However, as this paradox was driven by results from randomized studies, while subsequent observational studies rendered more conflicting results, these seemingly protective effects should still be interpreted with caution.”


Grymonprez M, Capiau A, De Backer TL, Steurbaut S, Boussery K, Lahousse L. The impact of underweight and obesity on outcomes in anticoagulated patients with atrial fibrillation: A systematic review and meta-analysis on the obesity paradox [published online March 26, 2021]. Clin Cardiol. doi: 10.1002/clc.23593