Coronary Microvascular Dysfunction and Cardiovascular Risk in Obese Patients
Key result
Lower CFR is linked to a ~95% increase in major adverse cardiovascular events.
- HR 1.95
- 95% CI 1.41-2.69
- P<0.001
- n=827
Why the study?
Additional discriminators of cardiovascular risk beyond BMI are needed in obese patients, and this study investigated the relationship among obesity, coronary microvascular dysfunction, and adverse outcomes.
Does coronary microvascular dysfunction (impaired CFR) predict adverse cardiovascular events independently of BMI in patients with suspected CAD and normal perfusion?
Key Points
- To investigate the relationship among obesity, coronary microvascular dysfunction, and adverse cardiovascular outcomes.
- Consecutive patients (N = 827) undergoing evaluation for coronary artery disease with stress positron emission tomography showing normal perfusion were followed for a median of 5.6 years.
- Blinded expert committee review adjudicated the primary composite endpoint of death or hospitalization for nonfatal myocardial infarction or heart failure.
- In adjusted analyses, a 1-U decrease in CFR remained independently associated with adverse events (adjusted hazard ratio: 1.95; 95% confidence interval: 1.41 to 2.69; p < 0.001), whereas a 10-U increase in BMI was not (adjusted hazard ratio: 1.20; 95% confidence interval: 0.95 to 1.50; p = 0.125), improving model discrimination (C-index 0.71 to 0.74).
- Obese patients with impaired CFR demonstrated a higher adjusted rate of events than those with preserved CFR (5.7% vs. 2.6%; p = 0.002), including those not meeting indications for bariatric surgery (6.4% vs. 2.6%; p = 0.04).
- An inverted independent J-shaped relationship linked BMI and CFR, with CFR decreasing linearly with increasing BMI in obese individuals (adjusted p < 0.0001).
Study Design
Type
Cohort (n=827)
Multicenter
No
Structured PICO
Does coronary microvascular dysfunction (impaired CFR) predict adverse cardiovascular events independently of BMI in patients with suspected CAD and normal perfusion?
P
Population
827 patients with suspected coronary artery disease and normal perfusion on cardiac stress PET, followed for a median of 5.6 years.
E
Exposure
Coronary microvascular dysfunction (CMD) assessed by impaired coronary flow reserve (CFR) via cardiac stress positron emission tomography (PET)
C
Comparator
Normal coronary flow reserve (CFR ≥1.7) or higher CFR values (evaluated continuously)
O
Outcome
Composite of death or hospitalization for nonfatal myocardial infarction or heart failurecomposite
Main Result
Hazard Ratio: 1.95 (95% CI 1.41–2.69)
p-value: p=<0.001
Coronary microvascular dysfunction, measured by impaired coronary flow reserve, is a stronger independent predictor of adverse cardiovascular events than BMI in obese patients with suspected CAD.
Limitations
- Single-center observational design
- Patients were clinically referred for PET myocardial perfusion imaging, introducing potential selection bias
- Did not address the impact of obesity-related noncardiac comorbidities
- Cohort size limited extensive subgroup analysis
- Residual confounding may persist despite adjustment for baseline differences
- single-center observational design
- referral bias (patients clinically referred for PET)
- potential for unmeasured confounding
- cohort size limited extensive subgroup analysis
- did not address impact of obesity-related noncardiac comorbidities
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“It's very useful information when you're trying to figure out whether someone referred for cardiac stress testing for chest pain is having pain due to epicardial disease or microvascular dysfunction, or some combination of the two.”
“Obesity is now one of the biggest global threats to cardiovascular health, yet body mass index — our main metric for defining obesity and thresholds for intervention — remains a controversial and flawed marker of cardiovascular prognosis. This is especially true in women, where high body mass index may reflect more 'benign' types of fat.”
Implication
CFR may refine event prediction beyond BMI in obese patients with suspected CAD; hypothesis-generating for microvascular-targeted strategies.
Abstract
BACKGROUND Besides body mass index (BMI), other discriminators of cardiovascular risk are needed in obese patients, who may or may not undergo consideration for bariatric surgery. Coronary microvascular dysfunction (CMD), defined as impaired coronary flow reserve (CFR) in the absence of flow-limiting coronary artery disease, identifies patients at risk for adverse events independently of traditional risk factors. OBJECTIVES The study sought to investigate the relationship among obesity, CMD, and adverse outcomes. METHODS Consecutive patients undergoing evaluation for coronary artery disease with cardiac stress positron emission tomography demonstrating normal perfusion (N = 827) were followed for median 5.6 years for events, including death and hospitalization for myocardial infarction or heart failure. RESULTS An inverted independent J-shaped relationship was observed between BMI and CFR, such that in obese patients CFR decreased linearly with increasing BMI (adjusted p < 0.0001). In adjusted analyses, CFR but not BMI remained independently associated with events (for a 1-U decrease in CFR, adjusted hazard ratio: 1.95; 95% confidence interval: 1.41 to 2.69; p < 0.001; for a 10-U increase in BMI, adjusted hazard ratio: 1.20; 95% confidence interval: 0.95 to 1.50; p = 0.125) and improved model discrimination (C-index 0.71 to 0.74). In obese patients, individuals with impaired CFR demonstrated a higher adjusted rate of events (5.7% vs. 2.6%; p = 0.002), even in those not currently meeting indications for bariatric surgery (6.4% vs. 2.6%; p = 0.04). CONCLUSIONS In patients referred for testing, CMD was independently associated with elevated BMI and adverse outcomes, and was a better discriminator of risk than BMI and traditional risk factors. CFR may facilitate management of obese patients beyond currently used markers of risk.
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Cite This Study
Bajaj et al. (2018) conducted a cohort in Suspected coronary artery disease (n=827). Coronary microvascular dysfunction (impaired coronary flow reserve) vs. Normal coronary flow reserve was evaluated on Composite of death or hospitalization for nonfatal myocardial infarction or heart failure (HR 1.95, 95% CI 1.41-2.69, p=<0.001). A 1-unit decrease in coronary flow reserve was independently associated with an increased risk of adverse cardiovascular events (HR 1.95) and improved risk discrimination over BMI.