Ten-Year Mortality in the WISE Study (Women’s Ischemia Syndrome Evaluation)

Abstract

Background The Women’s Ischemia Syndrome Evaluation (WISE) was a prospective cohort study of 936 clinically stable symptomatic women who underwent coronary angiography to evaluate symptoms and signs of ischemia. Long-term mortality data for such women are limited. Methods and Results Obstructive coronary artery disease (CAD) was defined as ≥50% stenosis on angiography by core lab. We conducted a National Death Index search to assess the mortality of women who were alive at their final WISE contact date. Death certificates were obtained. All deaths were adjudicated as cardiovascular (CV) or non-CV by a panel of WISE cardiologists masked to angiographic data. Multivariate Cox proportional hazards regression was used to identify significant independent predictors of mortality. At baseline, mean age was 58±12 years; 176 (19%) were non-white, primarily African American; 25% had a history of diabetes, 59% hypertension, 55% dyslipidemia, and 59% had a body mass index (BMI) ≥30. Over a median follow-up of 9.5 years (range 0.2 to 11.5 years) a total of 184 (20%) died. Of these, 115 (62%) were CV deaths; 31% of all CV deaths occurred in women without obstructive CAD (<50% stenosis). Independent predictors of mortality were obstructive CAD, age, baseline systolic blood pressure, history of diabetes, history of smoking, elevated triglycerides and estimated glomerular filtration rate. Conclusions Among women referred for coronary angiography for signs and symptoms of ischemia one in five died from predominantly cardiac etiologies within 9 years of angiographic evaluation. A majority of the factors contributing to the risk of death appear to be modifiable by existing therapies. Of note, one in three of the deaths in this cohort occurred in women without obstructive CAD, a condition often considered benign and without guideline-recommend treatments. Clinical trials are needed to provide treatment guidance for the group without obstructive CAD.

Ischemia and No Obstructive Coronary Artery Disease (INOCA): What Is the Risk?

“…Longer‐term follow‐up data from the WISE project confirmed a worse prognosis than previously thought for stable INOCA women where 10‐year all‐cause death and cardiac death rates were 17% and 11%, respectively, in women with nonobstructive CAD, and 10% and 6%, respectively, in women with normal coronary arteries 40. Furthermore, a recent meta‐analysis of 48 studies including patients presenting with stable symptoms undergoing either invasive or noninvasive coronary angiography demonstrated odds ratios of 1.57 to 1.7 for MACE defined as cardiac death, nonfatal MI, hospitalization for unstable angina, or revascularization in patients with NOCAD compared with their counterparts with normal coronary arteries.…”

“…Documented MACE rates in stable INOCA patients are summarized in Table 1 4, 10, 15, 26, 35, 36, 37, 38, 39, 40, 41. Additionally, many of these patients have an adverse quality of life, functional status, and exercise capacity with relatively frequent visits to healthcare providers for persistent or recurring disabling symptoms 42.…”

“…Comparison of primary, secondary prevention risk versus observed risk in an example of stable INOCA patient is presented in Figure 2 40, 47, 56, 63, 65, 66, 67, 68, 69, 70, 71. The primary prevention scores, developed in asymptomatic populations, predicted that risks vary between 1% and ≈5% and underestimate the observed INOCA risk.…”

Sex differences in heart failure

“…The 10‐year follow‐up from the WISE study demonstrated a 20% mortality rate in women referred for invasive angiography for symptoms of ischemia. In those who did not have obstructive disease, the 10‐year mortality was 13%, significantly greater than asymptomatic age‐matched controls (2.8%) …”

“…However, despite the lack of obstructive CAD, women who present with symptoms of angina have a higher mortality than asymptomatic females. The WISE (Women's Ischemic Syndrome Evaluation) study demonstrated that women experience symptoms of obstructive CAD differently than men, with older women more likely to present in a typical pattern . During their event, women may present with symptoms of shortness of breath (58%), weakness (55%), unusual fatigue (43%), diaphoresis (39%), and dizziness (39%) .…”