Association Between Coronary Vascular Dysfunction and Cardiac Mortality in Patients With and Without Diabetes Mellitus

Abstract

Background Diabetes increases the risk of adverse cardiac outcomes and is considered a coronary artery disease (CAD) equivalent. We examined whether coronary vascular dysfunction, an early manifestation of CAD, accounts for increased risk among patients with diabetes compared to non-diabetics. Methods and Results 2783 consecutive patients (1172 diabetics and 1611 non-diabetics) underwent quantification of coronary flow reserve (CFR=stress divided by rest myocardial blood flow) by PET and were followed for a median of 1.4 years (Q1–Q3: 0.7–3.2). The primary endpoint was cardiac death. Impaired CFR (below the median) was associated with an adjusted 3.2 and 4.9-fold increase in the rate of cardiac death for diabetics and non-diabetics, respectively (p=0.0004). Addition of CFR to clinical and imaging risk models improved risk discrimination both diabetics and non-diabetics (c-index: 0.77 to 0.79, p=0.04, and 0.82 to 0.85, p=0.03, respectively). Diabetic patients without known CAD with impaired CFR experienced a rate of cardiac death comparable to that for non-diabetic patients with known CAD (2.8 vs 2.0%/year, P=0.33). Conversely, diabetics without known CAD and preserved CFR had very low annualized cardiac mortality, which was similar to patients without known CAD or diabetes and normal stress perfusion and systolic function (0.3 vs. 0.5%/year, P=0.65). Conclusions Coronary vasodilator dysfunction is a powerful, independent correlate of cardiac mortality among both diabetics and non-diabetics and provides meaningful incremental risk stratification. Among diabetic patients without CAD, those with impaired CFR have event rates comparable to patients with prior CAD while those with preserved CFR have event rates comparable to non-diabetics.

Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC

“…In a large series of 1172 patients with diabetes compared with 1611 patients without diabetes, incorporation of MFR into PET assessment allowed identification of the 40% of diabetic patients who were at high risk (at equivalent risk to those with clinically recognized CAD) compared with the remainder, who experienced event rates comparable to individuals without diabetes. 102 Given the important limitations of relative MPI among diabetic patients, PET with quantification of blood flow is preferable to SPECT among patients with diabetes mellitus. Chronic Kidney Disease.…”

“…51,52,91 • A severely reduced global hyperemic MBF and MFR identify patients at high risk for major adverse cardiovascular events, including death. Although thresholds may vary in different labs using different software, in general an MFR of less than 1.5 should be considered a high-risk feature on MPI PET 46,49,50,53,92,94,98,102 and is associated with an Figure 8. Relationship between MFR and risk of cardiac death.…”

Cardiac 82Rb PET/CT for fast and non-invasive assessment of microvascular function and structure in asymptomatic patients with type 2 diabetes

“…Impaired CFR has previously been described as a powerful, independent correlate of cardiac mortality among patients with diabetes [8]. That study concluded that diabetic patients without known CAD and with impaired CFR experienced a rate of cardiac death comparable with that for non-diabetic patients with known CAD.…”

“…Among individuals without indications of CAD, microvascular dysfunction is associated with cardiovascular risk factors, including hypercholesterolaemia, diabetes, hypertension and smoking [7]. Moreover, it is a predictor of cardiac mortality [8]. Most patients with type 2 diabetes have associated hypertension, dyslipidaemia and obesity, all of which can contribute to coronary microvascular damage.…”

Prevalence and Clinical Significance of Discordant Changes in Fractional and Coronary Flow Reserve After Elective Percutaneous Coronary Intervention

“…Mehta et al reported that lower FFR values among acute coronary syndrome patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events 23. The principle of CFR has been vigorously applied to a number of diagnostic tests, although its sensitivity toward resting hemodynamic relevance has been considered an important limitation in its use to consider myocardial flow impairment, despite reported evidence of powerful efficacy to stratify the risk of adverse cardiac events 7, 16, 24, 25. Our results indicated that CFR decrease after successful PCI was not uncommon, and CFR decrease was associated with pre‐PCI physiological indices including high CFR, high FFR, low IMR, and no significant coronary flow increase after successful PCI.…”