Study Participants

The Heart and Soul Study is a prospective cohort study with the objective of evaluating psychosocial factors and health outcomes in patients with coronary disease. Methods and objectives have been described. We used administrative databases to identify outpatients with documented coronary artery disease (CAD) at 2 Department of Veterans Affairs Medical Centers (San Francisco Veterans Affairs Medical Center and the Veterans Affairs Palo Alto Health Care System, California), 1 university medical center (University of California, San Francisco), and 9 public health clinics in the Community Health Network of San Francisco. Patients were eligible to participate if they had at least 1 of the following: a history of myocardial infarction, angiographic evidence of at least 50% stenosis in 1 or more coronary vessels, prior evidence of exercise-induced ischemia by treadmill or nuclear testing, a history of coronary revascularization, or a diagnosis of CAD by an internist or cardiologist.

A total of 15,438 eligible patients were mailed an invitation to participate, and 2,495 responded that they would be interested. Of the 2,495 patients whom we attempted to contact by telephone to schedule a study appointment, 505 could not be reached and 596 declined to participate. An additional 370 patients were excluded because they had a history of myocardial infarction in the prior 6 months, deemed themselves unable to walk 1 block, or were planning to move out of the local area within 3 years.

Between September 2000 and December 2002, a total of 1024 participants enrolled, including 549 (54%) with a history of myocardial infarction, 237 (23%) with a history of revascularization but not myocardial infarction, and 238 (23%) with a diagnosis of CAD that was documented by their physician (based on a positive angiogram or treadmill test in > 98% of cases).

This protocol was approved by the following institutional review boards: the Committee on Human Research at the University of California, San Francisco; the Research and Development Committee at the San Francisco Veterans Affairs Medical Center; the Medical Human Subjects Committee at Stanford University; the Human Subjects Committee at the Veterans Affairs Palo Alto Health Care System; and the Data Governance Board of the Community Health Network of San Francisco. All participants provided written informed consent.

Data Collection

Each participant completed a detailed interview and questionnaire regarding age, gender, race, medical history, current smoking, and level of alcohol consumption. Echocardiographic studies were performed in the standard left lateral recumbent and supine positions with a commercially available ultrasound system with harmonic imaging (Acuson Sequoia, Siemens Corporation, Mountain View, CA). A single cardiologist (NBS), blinded to clinical and laboratory information, evaluated each comprehensive resting echocardiogram. ESV and LA volume were calculated using the biplane method of discs in the apical 4- and 2-chamber views at end systole, as recommended by the American Society of Echocardiography. LV mass was calculated from 2-dimensional wall thickness using the truncated ellipse method, using the semi-major and minor axis radius of the left ventricle.

Cardiovascular Outcomes

We conducted telephone follow-up interviews and questioned participants or their proxies regarding hospitalizations and mortality. Medical records, death certificates, and coroner’s reports were retrieved. Two blinded adjudicators reviewed each event, and if there was agreement the outcome classification was binding. If there was disagreement, a third blinded adjudicator reviewed the event and determined the outcome classification. All-cause mortality results were complete for at least 1 year of follow-up for 1,018 of 1,024 individuals. Five individuals were completely lost to follow-up, and 1 individual declined to participate further in the study.

Hospitalization for HF was defined as a clinical syndrome requiring a minimum one-night hospital stay and involving at least 2 of the following: paroxysmal nocturnal dyspnea, orthopnea, elevated jugular venous pressure, pulmonary rales, a third heart sound, cardiomegaly on chest radiography, or pulmonary edema on chest radiography. These clinical signs and symptoms must have represented a clear change from the normal clinical state of the patient and must have been accompanied by either failing cardiac output as determined by peripheral hypoperfusion (in the absence of other causes, eg, sepsis or dehydration) or peripheral or pulmonary edema treated with intravenous diuretics, inotropes, or vasodilators.

Mortality adjudications were based on hospital records, death certificates, and autopsy results. Death was considered due to cardiovascular (CV) causes if the death certificate listed acute myocardial infarction, congestive HF, or arrhythmia as the primary cause of death. Sudden death also was considered CV if it was unexpected, otherwise unexplained, and occurred within 1 hour of the onset of terminal symptoms.

Statistical Analysis

Baseline characteristics are reported as the mean plus or minus standard deviation for continuous variables and as percentages for categoric variables. Given the limitation of differentiating among risk factors by comparisons of hazard ratios (HRs) or c-statistic alone, we made calculations for both HR and c-statistic for each variable indexed to different parameters of body size. We used Cox proportional hazards (survival) models to calculate HR. To further explore our hypothesis that BSA is as useful as other methods of indexing for body size, we directly compared parameters indexed to basic values (BSA, height, BW, and BMI) with raw measurements using Pearson correlation coefficients. If excellent correlation was identified, less variation in predictive ability of indexing methods would be expected.

The c-statistics and HR are reported in radial plots, where the further distance from the center indicates higher c-statistics or HR. Figure 1 shows a sample radial plot for various echocardiographic variables measured among our population for the outcome of HF hospitalization. A symmetric circle would indicate equivalence among the different indexing parameters. Asymmetry of the image identifies variables with higher predictive ability as being further from the center. Analyses were performed using software (Statistical Analysis, Version 9.2, SAS Institute Inc, Cary, NC). Outcome events were counted once for each individual (eg, recurrent HF hospitalizations in the same participant were not counted). Predefined end points were HF hospitalization and all-cause mortality.

Radial plot of c-statistics, or area under the receiver operating characteristic curve, for standard echocardiographic variables in predicting HF hospitalization. Further distance from the center of the plot indicates higher predictive ability. LVEF , Left ventricular ejection fraction (%); LV ESV , left ventricular end-systolic volume (mL); EDV , end-diastolic volume (mL); LAV , left atrial volume (mL); RAV , right atrial volume (mL); EDPRv , end-diastolic pulmonary regurgitation velocity (m/s); TRv , TR velocity (m/s); MRv , mitral regurgitation velocity (m/s); PV s/d VTI , pulmonary vein systolic to diastolic flow ratio by velocity time integral (dimensionless ratio); IVRT , isovolumic relaxation time (ms).