Expert Review: Coronary Heart Disease

Association between coronary vascular dysfunction and cardiac mortality in patients with and without diabetes mellitus.

Background
Patients with diabetes mellitus are considered a high risk group for of adverse cardiac events even in the absence of overt myocardial ischemia or scar compared with patients without diabetes mellitus. Impaired coronary vascular function is an early manifestation of coronary artery disease (CAD) and is associated with adverse prognosis. Noninvasive measures of coronary vasodilator reserve integrate the hemodynamic effects of focal epicardial coronary stenosis, the fluid dynamic effects of diffuse atherosclerosis, and the presence of coronary microvascular dysfunction. Particularly, CFR is a quantitative measure of coronary vascular dysfunction and can be measured noninvasively with PET.

Knowledge Gap
The relationship between diabetes mellitus and cardiac risk reported in the literature is not consistent1-3. The identification of impaired coronary blood flow could help identify additional high-risk populations for therapy who are missed by current risk stratification methods.

Aim of the Study
The aim of the study was to assess if the presence of impaired coronary vasodilator function helps explain the observed excess risk of cardiac mortality among patients with diabetes mellitus and to compare the strength of this association with nondiabetics.

Methods
This is a single-center, prospective, longitudinal study including all consecutive patients referred for rest/stress cardiac PET and followed during a mean period of 1.4 years. The primary outcome was death resulting from any cardiac cause. Mortality resulting from any cause was used as a secondary end point

Results
The authors found that impaired CFR is associated with increased rates of cardiac mortality among both diabetics and nondiabetics and that the identification of coronary vasodilatador reserve results in similar improvement in risk discrimination and reclassification for both cohorts. Of note, CFR was consistently associated with higher rates of cardiac mortality regardless of the level of ischemia, scar extent, or left ventricular ejection fraction. The improvement in risk stratification was observed in 1 o 3 patients studied and was beyond comprehensive clinical assessment, LV systolic function, and semiquantitative measures of myocardial ischemia and scar. Importantly, diabetic patients without known CAD with impaired coronary vascular function experienced a rate of cardiac death (2.8%/year) comparable to and possibly higher than that for nondiabetic patients with known CAD (2.0%/year). Conversely, the rate of cardiac death in diabetic patients without known CAD was very low in the presence of relatively preserved coronary vascular function (0.3%/y). These findings may account in part for the inconsistent relationship between diabetes mellitus and cardiac risk reported in the literature1-3.

Conclusion
Coronary vasodilator dysfunction is a powerful, independent correlate of cardiac mortality among both diabetics and nondiabetics and provides meaningful incremental risk stratification. Among diabetic patients without CAD, those with impaired CFR have event rates comparable to those of patients with prior CAD, whereas those with preserved CFR have event rates comparable to those of nondiabetics.

Clinical Impact:
This finding reported on coronary vasodilator dysfunction could have implications for the classification of diabetes mellitus as a coronary disease risk equivalent. Specifically, only among diabetics with impaired vascular function is prognosis comparable to that of nondiabetic patients with known CAD.
The therapeutic implications of the observation that diabetics with impaired CFR have CAD-equivalent rates of cardiac death whereas those diabetics with preserved CFR have extremely favorable prognosis are uncertain and deserve further investigation. Specifically, whether impaired CFR can identify diabetics who will benefit from aspirin or other medical interventions with conflicting evidence among diabetics may warrant further exploration

Corresponding author from original paper
Marcelo F. Di Carli, MD, Brigham and Women’s Hospital, ASB-L1 037C, 75 Francis St, Boston, MA 02115.
E-mail mdicarli@partners.org

Citation: Circulation 2012; 126:1858

References:
1. Schramm TK, Gislason GH, Køber L, Rasmussen S, Rasmussen JN, Abildstrøm SZ, Hansen ML, Folke F, Buch P, Madsen M, Vaag A, Torp-Pedersen C. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk. Circulation. 2008;117:1945–1954.

2. Bulugahapitiya U, Siyambalapitiya S, Sithole J, Idris I. Is diabetes a coronary risk equivalent? Systematic review and meta-analysis. Diabet Med. 2009;26:142–148.

3. Wannamethee SG, Shaper AG, Whincup PH, Lennon L, Sattar N. Impact of diabetes on cardiovascular disease risk and all cause mortality in older men: influence of age at onset, diabetes duration, and established and novel risk factors. Arch Intern Med. 2011;171:404 – 410.

Citation: Circulation 2012; 126:1858

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