Coronary artery disease (CAD) is the leading cause of death among women both nationally and internationally. One of 3 women in the United States dies of cardiovascular disease.1 Since 1984, more women than men have died of CAD, and the mortality rate among women 35 to 44 years of age has been increasing on average by 1.3% for the past 12 years.2,3 Sixty-four percent of women who die suddenly of CAD have no previous symptoms.2 Over the past decade, research studies have highlighted the differences in the presentation of CAD symptoms in women compared with men as well as the sex discrepancy in the sensitivity of typical tests used to diagnose CAD.4-6 Inferior outcomes experienced by women following a cardiac event, such as a myocardial infarction, coronary angioplasty, or surgery, are also well documented in the literature.4,5,7 More recent research has been directed at identifying distinctive risk factors such as effects of homocystine and C-reactive protein levels on women and sex differences in the development of CAD.7-9
Cardiovascular disease results from a cascade of chronic inflammation and processes within the vascular system. Cardiac disease in women involves diffuse atherosclerosis, endothelial dysfunction, and microvascular disease.10 The generalized nature of cardiovascular disease is evidenced in studies that describe atherosclerosis in more than 1 vascular area at a time. For example, studies have found a significant correlation between peripheral arterial disease (PAD) and carotid artery stenosis and between PAD and CAD.11-15 However, one of the continuing challenges in clinical practice is identifying women at risk for cardiovascular disease and diagnosing disease before an event occurs.
Many patients with PAD are asymptomatic, so they do not present with complaints of claudication or cold extremities.16,17 Yet, PAD can be diagnosed in high-risk asymptomatic patients by completing an ankle brachial index (ABI), which may be completed in an outpatient setting.18,19 An ABI is performed by using a sphygmomanometer and a handheld Doppler to determine the systolic pressure in the dorsalis pedis or the posterior tibial artery on both the left and right sides while the patient is in a supine position. Once the ankle pressure is determined, a ratio is calculated by dividing the ankle pressure by the systolic brachial pressure from the corresponding side to determine the ABI. A ratio result of less than 0.90 mm Hg is diagnostic for PAD. Researchers suggest completing an ABI as part of a comprehensive cardiovascular assessment in high-risk individuals to diagnose PAD early in the disease process and hopefully reduce long-term consequences.20-22 The outcome of this approach is unclear as far as how it could impact early diagnosis of CAD in women.
In 2004, Otah et al23 completed a research that indicated that diagnostically low ABIs (<0.90 mm Hg) were predictive of the presence of severe CAD in African American patients. The following year, researchers found a significant correlation between low ABI values and presence of CAD as evidenced by coronary calcium scores.14 Findings from several studies also indicate that people with PAD are more likely to experience a coronary event, such as a myocardial infarction.11,12,24,25 Most of this research was retrospective in design and/or did not specifically focus on women.
Despite increased knowledge regarding the pathophysiology, disease trajectory, and unique symptom presentation of CAD in women, accurate and early diagnosis remains a difficult clinical task. Many complex factors account for the difficulty of diagnosing CAD in women. Thus, there is a need to continue identifying the benefit of low-risk diagnostic tools, in an effort to identify women with CAD before an event occurs. Therefore, the current study was designed prospectively to research the correlation of ABI results and presence of CAD in women, in an effort to investigate the potential use of the ABI as a prognostic tool to predict presence of CAD in women.
A prospective descriptive correlation design was used to investigate the relationship between ABI values and the presence of CAD in women. Potential study participants were determined from a computerized list of women scheduled for a diagnostic cardiac catheterization procedure during the data collection period. This information was obtained within Health Insurance Portability and Accountability Privacy Act guidelines since every patient had been provided with the hospital's Notice of Privacy Practice, which allows medical information to be used for research recruitment purposes only. Each woman who met the inclusion criteria (≥30 years old, medically stable as determined by staff nurse caring for patient, not in a critical care unit, and English speaking) was invited to participate prior to their cardiac catheterization procedure. Women who expressed interest in the study were given an opportunity to ask questions as part of the informed consent process. Eligible women who agreed to take part in the study were assigned a participant number to protect their identity. Demographic information and cardiovascular risk factor information were obtained from the hospital record and verified with the participant.
Protocol for ABI Measurement
An ABI measurement was performed on both legs prior to the cardiac catheterization procedure using the following protocol. Have participant in supine position for a minimum of 5 minutes prior to obtaining a measurement reading. Place sphygmomanometer around the arm just above the brachial artery; palpate artery; place diaphragm of stethoscope over brachial artery; inflate cuff to 200 mm Hg; deflate slowly; and record the pressure reading where the signal resumes. Place an appropriate-size sphygmomanometer around the lead just above the posterior tibial artery; apply conduction gel over the dorsalis pedis artery and listen with a Doppler to the pulse signal (may use tibial artery if necessary); inflate the cuff until the signal is no longer audible; and slowly deflate cuff and note the pressure when the signal becomes audible. Divide the ankle pressure by the brachial pressure to determine the ratio and record the ABI value. Repeat procedure on both legs.
Cardiac Catheterization Results
Written cardiac catheterization results were obtained following the procedure and dictation of results by each cardiologist. Catheterization results were then classified according to coronary disease found: no disease, 1-vessel disease, or multivessel disease. Catheterization results were then coupled with each woman's recorded ABI values and risk factors for analysis.
Data Analysis Plan
First, descriptive frequencies were determined for age and medical history indicative of cardiovascular risk: smoking, hypertension, hypercholesterolemia, diabetes mellitus, obesity, previous myocardial infarction, and stroke. Ankle brachial index results were categorized for frequency of normal (>0.90 mm Hg) or abnormal (<0.90 mm Hg) indicating presence of PAD. Cardiac catheterization results were categorized for frequency of no CAD, 1-vessel CAD, or multivessel CAD. Statistical t tests were run to analyze relationships between the identified cardiovascular risks and the presence and degree of CAD and the presence of PAD. Finally, an analysis of variance and χ2 tests were used to analyze the correlation of ABI values and the presence of CAD in these participants.
Thirty white women who met the inclusion criteria made up the sample. Mean age of the women in the sample was 65 ± 10.07 years, representing women aged 42 to 83 years undergoing a diagnostic cardiac catheterization procedure. A third of the women (33%) in this sample had a positive smoking history, and a third (33%) had been diagnosed with diabetes. Most women had hypertension (83.3%) and hypercholesterolemia (70%); yet, less than half of the women (40%) were obese. A little more than a quarter (26.7%) had already experienced a myocardial infarction, and a fifth of these women (20%) had had a stroke in the past.
Abnormal ABI values, diagnostic of PAD (<0.90 mm Hg), were found in 13.3% of women in the study. A significant correlation between age and ABI values was noted; the low ABI values were found in women of older age than normal ABI values (t = −2.30, P =.029). The older the woman, the lower the ABI measured, showing a significant negative correlation between age and ABI values, left (r = −0.39, P =.036) and right (r = −0.48, P =.009). Seventy-five percent of the abnormal ABIs were found in women 65 years or older.
Coronary Catheterization Results
Coronary artery disease, diagnosed by cardiac catheterization, was found in 82.1% of the women, whereas 17.9% were reported to have no disease. Of the women with CAD, more than half (57.1%) were diagnosed with multivessel CAD. There was no statistical difference in the presence of CAD in women younger than 65 years compared with women 65 years or older (χ2 =.451, P =.50). Older women were significantly more likely to have multivessel CAD rather than no disease on the cardiac catheterization (F = 3.86, P =.035).
Correlation of ABI and CAD Diagnosed by Catheterization
The main question of interest was the relationship between ABI and CAD based on catheterization results. No significant differences were found between the means of the actual ABI values for women with no CAD, 1-vessel CAD, or with multivessel CAD using analysis of variances (left: F = 2.39, P =.113; right: F = 2.81, P =.08).
A χ2 test failed to reveal any significant differences between presence or absence of PAD based on ABI results and the diagnosis of no CAD, 1-vessel CAD, or multivessel CAD. The interesting finding was that all of the women with ABI of less than 0.90 mm Hg had CAD based on the cardiac catheterization report; however, all of the women with CAD did not have abnormal ABI results, explaining the lack of a statistically significant correlation between ABI results and CAD diagnosis in this study.
The unexpected finding of a lack of a statistically significant correlation between ABI values and diagnosis of CAD by cardiac catheterization raised several questions. Was it too early in the trajectory of the vascular disease process to detect PAD? Or were some of these women experiencing nonobstructive CAD, which was not identifiable using a traditional cardiac catheterization? Is there a protective female hormone at work affecting the ABI values at younger ages? Was the sample size too small?
As noted earlier, previous research has documented a significant correlation between PAD and CAD, but either has been retrospective or did not focus primarily on women. Findings from this study contradict results from similar research conducted on a group of African American men and women who had comparable percentages of comorbidities and risk factors.23 Otah and colleagues23 found a significant correlation between ABI values and multivessel CAD, but not 1-vessel CAD in their study. An initial power analysis used to determine the ideal sample size for this study was based on this previous research; however, post hoc power analysis indicated the need for sample size of between 130 and 160. Thus, unexpected lack of a significant correlation between ABI values and presence of CAD in this study may be a consequence of the small sample size, which also limits the use of some statistical tests. Inclusion of women at younger ages in this study may contribute to the lack of consistency in the results of the current study with some earlier research. There is a very large variation of age of women in the sample, from 42 to 83 years old. Also, the inclusion of women with previous myocardial infarction may have influenced the results.
Cardiac catheterization procedures using traditional techniques, such as that used in this study, only reveal coronary artery occlusive disease as opposed to nonobstructive coronary disease that may be present but remains undetected by the traditional methods. Researchers are now suggesting a new paradigm for understanding cardiac disease in women and continuing to build knowledge of sex differences in all cardiovascular diseases. Some researchers suggest a clustering of risk factors such as C-reactive protein and homocystine levels, metabolic syndrome, and PAD, in an effort to assess CAD risk in women. Others are focusing on new diagnostic procedures that may improve the early diagnosis of CAD in women. For example, Bairey-Mertz and colleagues26,27 have developed a unique cardiac catheterization procedure for women that identifies coronary artery dysfunction by injecting vasoactive medication into the arteries during the procedure.5,9,28 Because women tend to develop more diffuse CAD, typical narrowing of the coronary artery in one particular area often is not evident on traditional cardiac catheterization. Yet, diffuse coronary disease and decreased flow may be visualized using this new technique. Thus, the term nonobstructive coronary artery disease has been used to describe "atypical" cardiac catheterization findings in the setting of women with cardiac abnormalities noted on nuclear imaging tests.5 As noted above, this phenomenon may have impacted the results of the current study, which focused solely on women undergoing a traditional cardiac catheterization.
Women continue to have a risk of developing and dying of all types of cardiovascular diseases. Research over the past decade provides evidence of the need for sex-specific studies of the pathophysiology and manifestation of cardiac disease. This study failed to show the expected correlation between low ABI values and CAD, but did show a significant influence of age and presence of both PAD and CAD. Future research should focus on continuing to investigate the predictive use of the ABI, focusing on women who are noted to be at risk for cardiac disease based on both traditional and newly defined risk factors such as C-reactive protein and homocystine. In addition, CAD should be diagnosed using innovative tests to detect not only obstructive but also nonobstructive CAD in women.
The author thanks the following individuals, who were instrumental in conduction of this study: Twilla Walker, FNP; Denise Highsmith, RN; Joellen Edwards, PhD; and Debi Pfortmiller, Statistician.
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