The incidence of diabetes mellitus (DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide.A close link exists between DM and cardiovascular disease (CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients.Cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events.In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients.Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease.This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions.

Introduction: The traditional focus of cardiac care on obstructive (>70% stenosis) CAD potentially distracts from the risks inherent in non-obstructive CAD. However, surprisingly little is known about non-obstructive CAD outcomes. Therefore, we determined the association between non-obstructive CAD and cardiovascular outcomes. Methods: Using the national VA CART program, we studied all veterans undergoing elective coronary angiography for angina between October 2007 and September 2012. Patients were categorized by CAD extent (none (no stenosis >20%), non-obstructive (no stenosis >=70%), obstructive (any stenosis >=70%)) and distribution (1, 2, or 3 vessel), and assessed for major adverse cardiac events (MACE), defined as all-cause mortality and MI. We adjusted for demographic, clinical, and treatment factors using Cox proportional hazards modeling. Secondary analyses sub-divided non-obstructive CAD into mild (20-49% stenosis) and moderate (50-69% stenosis) disease. Results: During the study period, 40,872 veterans underwent catheterization. Of these, 8411 (20.6%) had no CAD, 5219 (17.7%) had 1V non-obstructive CAD, 3034 (10.3%) had 2V non-obstructive CAD, 1388 (4.7%) had 3V non-obstructive CAD, 8588 (29.1%) had 1V obstructive, 5227 (17.7%) had 2V obstructive, and 6017 (20.4%) had 3V/LM obstructive CAD. MACE rates progressively increased with increasing CAD severity (Figure). This association persisted after risk adjustment (HR 1.28 (1.08, 1.51) for 1V non-obstructive, 1.29 (1.08, 1.52) 2V non-obstructive, 1.44 (1.12, 1.86) 3V non-obstructive, 1.93 (1.64, 2.28) 1V obstructive, 2.73 (2.28, 3.27) 2V obstructive, and 2.98 (2.52, 3.53) 3V/LM obstructive CAD)). A trend toward higher MACE in moderate 3V non-obstructive compared to 1V obstructive CAD (HR 1.34 (0.71, 2.52)) was noted. Conclusions: Non-obstructive CAD, relative to no CAD, is associated with 28-44% higher odds of MACE. MACE risk progressively increases by CAD extent, rather than abruptly increasing between non-obstructive and obstructive CAD. The risks of adverse events were similar for 3V non-obstructive CAD and 1V obstructive CAD, highlighting the limitations of a dichotomous characterization of angiographic CAD and a need to recognize the risks inherent in non-obstructive CAD.

IMPORTANCE:Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD).OBJECTIVE:To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort.DESIGN, SETTING, AND PARTICIPANTS:Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded.EXPOSURES:Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ≥1 stenosis ≥20% but no stenosis ≥70%; obstructive CAD: any stenosis ≥70% or left main [LM] stenosis ≥50%) and distribution (1, 2, or 3 vessel).MAIN OUTCOMES AND MEASURES:The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality.RESULTS:Among 37,674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome.CONCLUSIONS AND RELEVANCE:In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients.