Coronary Microvascular Dysfunction and Cardiovascular Risk in Obese Patients

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.

Keywords: bariatric surgery; body mass index; coronary microvascular dysfunction; obesity; prognosis.

FIGURE 1. Coronary Flow Reserve Is Inversely Associated With Body Mass Index in Obese Patients

An inverted J–shaped relationship between coronary flow reserve and body mass index is illustrated using a restricted cubic spline linear regression model with 95% confidence intervals (orange); patient frequency histograms are shown for body mass index (blue). Model is adjusted for demographic and clinical risk factors (age, sex, race, hypertension, diabetes, peripheral vascular disease, chronic obstructive pulmonary disease, atrial fibrillation, tobacco use, estimated glomerular filtration rate, beta-blocker use, and left ventricular ejection fraction).

FIGURE 2. Relationship Between Body Mass Index and Annualized Rate of Adverse Events

Relationship (A) adjusted for age only and (B) adjusted for demographic and clinical risk factors, including coronary flow reserve (also age, sex, race, hypertension, diabetes, peripheral vascular disease, chronic obstructive pulmonary disease, atrial fibrillation, tobacco use, estimated glomerular filtration rate, beta-blocker use and left ventricular ejection fraction). Restricted cubic spline Poisson regression models with 95% confidence intervals are shown in orange; patient frequency histograms appear in blue.

FIGURE 3. Relationship Between Coronary Flow Reserve and Annualized Rate of Adverse Events

Relationship (A) adjusted for age only and (B) adjusted for demographic and clinical risk factors, including body mass index (also age, sex, race, hypertension, diabetes, peripheral vascular disease, chronic obstructive pulmonary disease, atrial fibrillation, tobacco use, estimated glomerular filtration rate, beta-blocker use, and left ventricular ejection fraction). Restricted cubic spline Poisson regression models with 95% confidence intervals are shown in orange; patient frequency histograms appear in blue.

FIGURE 4. Adjusted Cumulative Hazard of Adverse Events in Obese Patients According to Coronary Flow Reserve

Obese patients with impaired coronary flow reserve experienced increased adjusted risk of events. Curves are adjusted for age, sex, race, hypertension, diabetes, peripheral vascular disease, chronic obstructive pulmonary disease, atrial fibrillation, tobacco use, estimated glomerular filtration rate, beta-blocker use, and left ventricular ejection fraction. BMI = body mass index; CFR = coronary flow reserve.

FIGURE 5. Adjusted Annualized Rate of Adverse Events Among Categories of Obese Patients by Coronary Flow Reserve

In obese patients, those with impaired coronary flow reserve demonstrated a higher adjusted annualized rate of adverse events (overall p = 0.002). In those without extreme obesity (BMI 30 to 39 kg/m²), this occurred irrespective of whether they met current indications for bariatric surgery. Plots are adjusted for age, sex, race, hypertension, diabetes, peripheral vascular disease, chronic obstructive pulmonary disease, atrial fibrillation, tobacco use, estimated glomerular filtration rate, beta-blocker use, and left ventricular ejection fraction. Abbreviations as in Figure 4.

CENTRAL ILLUSTRATION. Obesity, Coronary Microvascular Dysfunction, and Cardiovascular Risk

Schematic of heterogeneity of risk among obese patients, and a potential role for coronary flow reserve to better phenotype patients by identifying those with coronary microvascular dysfunction. Higher-risk obese patients may be more likely to benefit from interventions such as bariatric surgery than lower-risk obese patients.