Obesity Paradox Prevails for PCI in Women

Patrice Wendling

January 15, 2018

NEW YORK CITY — Adjusted analyses from the largest study so far examining the effects of body mass index (BMI) in women undergoing PCI with a drug-eluting stent (DES) show that BMI had no effect on adverse cardiac events, that being overweight or mildly obese conferred a survival benefit, and being underweight increased the risk for all-cause and cardiac death more than twofold.[1]

At 3 years, all-cause mortality was 28% lower in overweight women and 24% lower in obese women compared with normal-weight women but trended up 20% in the severely obese.

The findings are consistent with those observed in men undergoing PCI but also call attention to the higher risks known to exist for underweight women, senior author, Dr Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, NY), told theheart.org | Medscape Cardiology.

"The fact that we didn't show more MIs, more recurrent revascularizations, and other end points is not as significantly important as us understanding that the all-cause mortality, when you correct for everything after PCI in these small, frail ladies, is much higher," Mehran said. "We need to pay special attention to these patients, understand what their follow-up is, and how to care for them."

The J-shaped relationship between mortality and BMI after PCI has been shown in mixed-sex cohorts, but evidence of an obesity paradox in female patients undergoing contemporary PCI is very limited. Further, it's been suggested that mortality after PCI may be higher in overweight and obese female patients than in their male counterparts, note the investigators, led by Dr Michela Faggioni (Mount Sinai Hospital and University Hospital of Pisa, Italy).

The study, published in the January 8 issue of JACC Cardiovascular Interventions, provides a unique opportunity to examine the obesity paradox concept, with pooled patient-level data from 9420 women with CAD treated with a DES in 26 randomized PCI trials. On the basis of BMI, 1% were underweight (<18.5 kg/m2), 29% normal weight (18.5 to 24.9 kg/m2), 36% overweight (25 to 29.9 kg/m2), 20% obese (30 to 34.9 kg/m2), and 13% morbidly obese (≥35 kg/m2).

During the 3-year follow-up, 1285 major adverse cardiovascular events (MACE)—a composite of death, MI, target lesion revascularization (TLR), or definite or probable stent thrombosis—and 440 deaths occurred.

Unadjusted risks for MACE, all-cause mortality, and cardiac death were significantly higher in underweight patients than normal-weight patients, while the risks were lower in overweight, obese, and severely obese women.

After multivariate adjustment, however, rates of CV events were similar across BMI groups, while the risk for death remained higher in the underweight.

Table. Adjusted Risks (95% Confidence Intervals) of 3-Year Adverse Outcomes by BMI Group

Variable <18.5 kg/m2 18.5–24.9 kg/m2 25–29.9 kg/m2 30-34.9 kg/m2 ≥35 kg/m2
MACE 1.35 (0.88–2.07) 1.0 (reference) 0.88 (0.75–1.03) 0.91 (0.75–1.09) 0.84 (0.67–1.06)
Death 2.20 (1.31–3.71) 1.0 (reference) 0.72 (0.55–0.94) 0.76 (0.55–1.05) 1.20 (0.83–1.75)
Cardiac death 2.18 (1.07–4.44) 1.0 (reference) 0.82 (0.57–1.17) 0.89 (0.58–1.37) 1.22 (0.73–2.04)
MI 1.06 (0.25–4.43) 1.0 (reference) 0.99 (0.64–1.52) 1.23 (0.77–1.98) 1.03 (0.58–1.81)
TLR 1.22 (0.56–2.63) 1.0 (reference) 1.23 (0.96–1.57) 1.00 (0.74–1.33) 0.86 (0.61–1.21)
Definite/probable stent thrombosis 2.00 (0.47–8.54) 1.0 (reference) 1.11 (0.64–1.90) 1.47 (0.83–2.62) 0.83 (0.39–1.77)


"Number one, we need to look at frailty as an important indicator that is not usually collected," Mehran said. "It comes back again to the quality of life and important issues that we have to be able to collect in our case report forms and in patient demographics, especially in the female patient population."

The small number of underweight patients, at just 139, is a limitation, but Mehran said the study reveals important insights into these patients. At presentation, underweight patients were older and more likely to be current or past smokers, have more type B2/C lesions, and require longer stent lengths. Underweight as well as normal-weight and overweight women were also more likely to undergo PCI for higher-risk acute coronary syndromes than obese and severely obese women.

Obese women had a lower prevalence of multivessel disease but had more cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes, and family history of CAD. Notably, severely obese and underweight patients were both more likely to be treated with an early-generation DES.

In a related editorial,[2] Drs Michael P Savage and David L Fischman (both from Thomas Jefferson University Hospital, Philadelphia, PA) observe that being overweight or modestly obese may confer a protective effect through as-yet undetermined mechanisms, but they question whether big is indeed better and whether current attitudes and guidelines on secondary prevention should be revised.

"This question is the elephant in the room rarely addressed in publications on the obesity paradox. In our opinion, it is far too premature to change clinical practice especially since there are alternative explanations for the apparent paradox," they write.

Savage and Fischman point out that angiographic resolution can be significantly reduced in larger patients, which may make operators averse to attempting higher-risk procedures. Another confounding factor is the higher use of radial access in obese patients, which is associated with less bleeding and lower mortality in selected patients undergoing PCI. Finally, studies have shown that obese patients are treated more aggressively with guideline-directed intensive medical therapies than nonobese patients, which could contribute to the favorable outcomes in these patients.

"Nevertheless, it's hard to refute that at least for the short term, overweight and mildly obese patients seem to fare better after PCI. Longer-term studies are needed to determine whether higher BMI patients demonstrate a clinical catch-up during later follow-up due to excess cardiovascular risk factors," the editorialists write.

Mehran reports receiving institutional research grant support from Eli Lilly/Daiichi-Sankyo, Bristol-Myers Squibb, AstraZeneca, The Medicines Company, OrbusNeich, Bayer, Abbott, Watermark Research Partners, Novartis, Medtronic, and AUM Cardiovascular; serving on the executive committee of and receiving fees from Janssen Pharmaceuticals and Osprey Medical; and receiving consulting fees from Medscape, The Medicines Company, Boston Scientific, Merck, Cardiovascular Systems, Sanofi, Shanghai BraccoSine Pharmaceuticals, and AstraZeneca. Faggioni has disclosed no relevant financial relationships; other coauthor disclosures are listed in the paper. Savage and Fischman have disclosed no relevant financial relationships.

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