Little is known about electrocardiographic (ECG) characteristics of menopausal women with or at increased risk of coronary heart disease (CHD). Data from 10,101 participants in the Raloxifene Use for The Heart (RUTH) trial were used to correlate baseline ECG abnormalities with clinical characteristics. Baseline characteristics that were statistically significantly associated (p ≤0.05) with ECG findings in univariate analyses were used to derive multivariate model selection. Of 59% normal electrocardiograms, 50% were from women with CHD and 69% from women at increased risk of CHD. In the women with CHD, 59% reported a previous myocardial infarction (MI); 43% had a normal electrocardiogram, and 49% had a definite ECG Q-wave MI. Women in the increased-risk group had not reported a previous MI, yet 11% had a definite ECG Q-wave MI. Of women reporting hypertension, 35% had ECG evidence of left ventricular hypertrophy, but 58% did not have an abnormal electrocardiogram. Significantly more women with diabetes in the increased-risk and documented CHD cohorts had abnormal electrocardiograms (p <0.01 for the 2 cohorts). Percent abnormal electrocardiograms increased with increasing age (55 to 64, 65 to 74, and ≥75 years, p <0.01) in all cohorts. Angina and coronary artery bypass graft surgery, but not percutaneous coronary intervention, predicted an abnormal electrocardiogram. In conclusion, there were high percentages of normal electrocardiograms in the increased-risk and documented CHD groups of RUTH participants, with substantial discrepancy between MI history and ECG MI documentation, and increasing age was the predominant correlate with an abnormal electrocardiogram in all 3 cohorts.
Limited information is available about electrocardiographic (ECG) characteristics of menopausal women with documented coronary heart disease (CHD) or at increased risk of CHD. The Raloxifene Use for The Heart (RUTH) study offers a database for correlation of baseline ECG abnormalities with clinical characteristics of the study population. The objective of the RUTH trial was to ascertain whether raloxifene 60 mg/day versus placebo decreased the occurrence of coronary death, nonfatal myocardial infarction (MI), hospitalization due to acute coronary syndrome, and invasive breast cancer. Study results were previously published. Briefly, raloxifene decreased the incidence of invasive breast cancer but had no significant effect on coronary events. The purpose of the present study was to ascertain the relation of baseline ECG abnormalities to coronary risk characteristics and previous coronary events, with particular attention to MI, hypertension, and age, to assess whether ECG abnormalities offer added clinical value.
Methods
The RUTH trial enrolled 10,101 women (≥55 years old) at 177 sites in 26 countries. Participants were 5,070 women with increased risk of CHD and 5,031 women with documented CHD. Characteristics of the RUTH population are presented in Table 1 and described in detail elsewhere.
| Variable | All Patients | Increased CHD Risk | Documented CHD |
|---|---|---|---|
| (n = 10,101) | (n = 5,070) | (n = 5,031) | |
| Age (years) | 67.6 ± 6.7 | 67.5 ± 6.8 | 67.6 ± 6.5 |
| Age ≥70 years | 3,931 (39%) | 2,033 (40%) | 1,898 (38%) |
| Height (cm) | 158.0 ± 6.8 | 157.6 ± 6.8 | 158.5 ± 6.8 |
| Weight (kg) | 71.9 ± 13.9 | 72.9 ± 14.7 | 70.9 ± 12.9 |
| Body mass index (kg/m 2 ) | 28.8 ± 5.1 | 29.3 ± 5.5 | 28.2 ± 4.8 |
| Body mass index ≥27 kg/m 2 | 5,994 (60%) | 3,185 (63%) | 2,809 (56%) |
| Waist circumference (cm) | 93.9 ± 13.2 | 95.5 ± 13.5 | 92.2 ± 12.6 |
| Systolic blood pressure (mm Hg) | 146 ± 21 | 147 ± 20 | 144 ± 21 |
| Diastolic blood pressure (mm Hg) | 82 ± 10 | 83 ± 10 | 81 ± 10 |
| Heart rate (beats/min) | 71 ± 10 | 73 ± 10 | 69 ± 11 |
| Ethnicity | |||
| Caucasian | 8,481 (84%) | 4,128 (81%) | 4,353 (87%) |
| Hispanic | 520 (5%) | 414 (8%) | 106 (2%) |
| East Asian | 505 (5%) | 246 (5%) | 259 (5%) |
| Afro-Caribbean | 129 (1%) | 75 (1%) | 54 (1%) |
| West Asian | 77 (1%) | 23 (<1%) | 54 (1%) |
| Other | 391 (4%) | 181 (4%) | 210 (4%) |
| Current smoker | 1,256 (12%) | 884 (17%) | 372 (7%) |
| Exposure to secondary smoke | 2,598 (26%) | 1,359 (27%) | 1,239 (25%) |
| Alcohol consumption | |||
| ≥1 drink/week | 1,746 (17%) | 770 (15%) | 976 (19%) |
| <1 drink/week | 2,581 (26%) | 1,262 (25%) | 1,319 (26%) |
| None | 5,329 (57%) | 3,034 (60%) | 2,295 (54%) |
| Physical activity at work/leisure | |||
| High | 808 (8%) | 403 (8%) | 405 (8%) |
| Moderate | 5,350 (53%) | 2,615 (52%) | 2,735 (55%) |
| Minimum | 3,937 (39%) | 2,013 (40%) | 1,924 (38%) |
| Vigorous activity >2 times/week | 2,477 (25%) | 1,092 (22%) | 1,385 (28%) |
| History of cardiac rehabilitation | 1,462 (14%) | 136 (3%) | 1,326 (26%) |
| Number of years postmenopausal | 19.4 ± 8.8 | 19.1 ± 9.0 | 19.7 ± 8.6 |
| Hysterectomy | 2,319 (23%) | 1,180 (23%) | 1,139 (23%) |
| Previous use | |||
| Estrogen replacement therapy | 1,399 (14%) | 603 (12%) | 796 (16%) |
| Estrogen/progestin replacement therapy | 605 (6%) | 301 (6%) | 304 (6%) |
| Oral contraceptives | 1,930 (19%) | 777 (15%) | 1,153 (23%) |
| Number of years using estrogen or estrogen/progestin | 4.1 ± 5.4 | 3.9 ± 4.9 | 4.3 ± 5.7 |
| Diabetes mellitus | 4,607 (46%) | 3,265 (64%) | 1,342 (27%) |
| Systemic hypertension | 7,863 (78%) | 4,310 (85%) | 3,553 (71%) |
| Previous myocardial infarction | 2,950 (29%) | 0 (0%) | 2,950 (59%) |
| Previous coronary bypass graft | 1,654 (16%) | 0 (0%) | 1,654 (33%) |
| Previous percutaneous intervention | 1,690 (17%) | 0 (0%) | 1,690 (34%) |
| Previous angina pectoris ⁎ | 3,341 (33%) | 0 (0%) | 3,341 (66%) |
| Lower extremity arterial disease | 1,083 (11%) | 683 (13%) | 400 (8%) |
| Abnormal electrocardiogram † | 7,448 (41%) | 4,978 (31%) | 2,470 (50%) |
| Electrocardiographic Q-wave myocardial infarction | 1,116 (11%) | 170 (3%) | 946 (19%) |
| Total cholesterol (mg/dl) | 218.7 ± 44.5 | 224.5 ± 44.0 | 212.8 ± 44.2 |
| Low-density lipoprotein cholesterol (mg/dl) | 121.9 ± 37.3 | 125.4 ± 37.1 | 118.4 ± 37.1 |
| High-density lipoprotein cholesterol (mg/dl) | 52.4 ± 14.3 | 53.0 ± 15.0 | 51.9 ± 13.6 |
| Triglycerides (mg/dl) | 159.0 ± 110.8 | 163.7 ± 114.4 | 154.2 ± 106.8 |
| Fasting glucose (mmol/L) | 7.7 ± 3.5 | 8.4 ± 3.8 | 6.9 ± 3.0 |
| Hemoglobin A 1c ‡ | 7.2 ± 1.6 | 7.5 ± 1.8 | 6.8 ± 1.4 |
| Fibrinogen (mg/L) § | 355.3 ± 81.1 | 353.3 ± 80.8 | 358.0 ± 81.7 |
⁎ With angiographically confirmed coronary heart disease.
† Definite Q-wave myocardial infarction; pathologic ST-T depression; conduction disturbances excluding first-degree atrioventricular block, atrial fibrillation or flutter; or ventricular hypertrophy.
‡ n = 9,795, 4,910, and 4,885 for overall, increased risk for coronary heart disease, and documented coronary heart disease, respectively.
§ n = 520, 302, and 218 for overall, increased coronary heart disease risk, and documented coronary heart disease, respectively.
Documented CHD required evidence of MI, myocardial revascularization, or angina with ≥50% angiographic obstruction of a major coronary artery. Increased CHD risk status required 4 points using a predefined scale that encompassed older age, diabetes mellitus, hypertension, hyperlipidemia, and current cigarette smoking ( Table 2 ).
| Points for coronary heart disease † | |
| Myocardial infarction 3–36 months before randomization | 4 |
| Angina pectoris with coronary disease documented by angiogram | 4 |
| Catheter-based coronary revascularization 6–36 months before randomization | 4 |
| Coronary artery bypass grafting 3–36 months before randomization | 4 |
| Myocardial infarction >36 months before randomization | 2 |
| Catheter-based coronary revascularization >36 months before randomization | 2 |
| Coronary artery bypass grafting >36 months before randomization | 2 |
| Points for coronary heart disease risk factors | |
| Lower extremity arterial disease documented by symptoms, ankle/brachial index <0.9, revascularization, or nontraumatic amputation | 4 |
| Current smoker + systemic hypertension + hyperlipidemia ‡ | 4 |
| Diabetes mellitus § | 3 |
| Age ≥70 years | 1 |
| Age ≥65–<70 years | 1 |
| Hyperlipidemia | 1 |
| Current smoker by self-report ∥ | 1 |
| Systemic hypertension ¶ | 1 |
⁎ At least 4 risk points required for enrollment.
† Can be additive to points for coronary heart disease risk factors.
‡ Low-density lipoprotein cholesterol >160 mg/dl or high-density lipoprotein cholesterol <45 mg/dl with triglycerides >250 mg/dl or on medication.
§ Fasting plasma glucose >140 mg/dl or on medication.
∥ At least 10 cigarettes/day for 6 months before enrollment.
¶ Systolic blood pressure >160 mm Hg or diastolic blood pressure >95 mm Hg or on medication.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
