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Comparative Study
. 2014 Nov 5;312(17):1754-63.
doi: 10.1001/jama.2014.14681.

Nonobstructive coronary artery disease and risk of myocardial infarction

Thomas M Maddox  1 , Maggie A Stanislawski  2 , Gary K Grunwald  3 , Steven M Bradley  1 , P Michael Ho  1 , Thomas T Tsai  4 , Manesh R Patel  5 , Amneet Sandhu  6 , Javier Valle  6 , David J Magid  7 , Benjamin Leon  6 , Deepak L Bhatt  8 , Stephan D Fihn  9 , John S Rumsfeld  1
Affiliations
Comparative Study

Nonobstructive coronary artery disease and risk of myocardial infarction

Thomas M Maddox et al. JAMA. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Patel reported having received grants from the National Heart, Lung, and Blood Institute–PROMISE Trial, Johnson and Johnson, and the Agency for Healthcare Research and Quality. Dr Bhatt reported having served on an advisory board for Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; on the board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; as a chair for the American Heart Association Get With The Guidelines Steering Committee; and on data monitoring committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; having received honoraria from the American College of Cardiology (Editor, Clinical Trials, Cardiosource), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), and WebMD (CME steering committees); having served as editor for Clinical Cardiology (Associate Editor) and the Journal of the American College of Cardiology (Section Editor, Pharmacology); having received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, sanofi-aventis, and The Medicines Company; and having performed unfunded research for FlowCo, PLx Pharma, and Takeda. No other disclosures were reported.

Figures

Figure 1
Figure 1. Time-to-Event Plots for 1-Year Myocardial Infarction, Mortality, and Combined Myocardial Infarction and Mortality,by CAD Extent
CAD indicates coronary artery disease; LM, left main.
Figure 2
Figure 2. Adjusted Cox Model Results for 1-Year Myocardial Infarction, Mortality, and Combined Myocardial Infarction and Mortality by CAD Extent, Relative to No Apparent CAD
CAD indicates coronary artery disease; HR, hazard ratio.
See this image and copyright information in PMC

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