Angiography for female patients who have presented with symptoms of cardiac distress appear to be not effective in determining the possible extent of coronary artery disease that may actually exist, according to new research. Therefore, new ways of diagnosing women need to be developed or perfected, according to a series of studies resulting from the Women’s Ischemia Syndrome Evaluation (WISE) study sponsored by the National Heart, Lung and Blood Institute (Bethesda, Maryland) and published in a supplement to the Feb. 7 issue of the Journal of the American College of Cardiology. The researchers concluded that “about one-half of the women referred to a cardiology practice for suspected ischemia do not have obstructive coronary disease, yet their prognosis is not benign in terms of future events and persistent symptoms,” according to the introduction to the series.

In an article in the Los Angeles Times in early March, Dr. C. Noel Bairey Merz of Cedars-Sinai Medical Center (Los Angeles) said, “One of the biggest take-home messages from this study is that we must stop falsely reassuring women when their arteries are open.” Instead of large blockages, postmenopausal women are more prone to a condition that leads to a narrowing of the microvasculature throughout the coronary artery system, rather than a large clump of plaque in one artery that can easily be seen with angiography. “The WISE study has further demonstrated that microvascular ischemia is frequently associated with the signs and symptoms of this large cohort of women with nonobstructive coronary arteries,” the researchers said.

Specifically, according to the State-of-the-Art portion of the series, the Duke Activity Status Index (DASI), a 12-question self-report, “provides valid information predictive of adverse cardiovascular outcomes.” According to the study introduction: “Perhaps this instrument, if validated in other female populations, should be administered in the office as a part of our diagnostic evaluation,” according to the study introduction.

The study also suggested that exercise testing on a treadmill to increase heart rate, often called “stress testing,” may be questionable when it comes to its ability to predict adverse events in women. The study said that because SPECT perfusion techniques measure deficits based upon “differences in regional distribution of blood flow that is comparatively assessed . . . across the myocardium,” it is possible that “in the setting of global coronary vascular dysfunction (endothelial or microvascular dysfunction), the SPECT study could show no regional differences in the distribution of flow and appear normal,” even when there was cause for concern.

Dutch study finds many undiagnosed MIs

Dutch researchers who analyzed more than 4,000 men and women over 55 to see how many heart attacks went undiagnosed at the time they occurred, found that the figure was more than four in 10. The results come from an analysis of a large proportion of the men and women involved in the Rotterdam Study, a prospective population study investigating chronic disabling diseases. A total of 5,148 participants with no evidence of prevalent myocardial infarction (MI) were enrolled from 1990 to 1993.

The report was published in the Feb. 14 edition of European Heart Journal, the journal of the European Society of Cardiology (Sophia Antipolis, France). The authors, who are from the department of epidemiology and biostatistics at Erasmus Medical Center (Rotterdam, the Netherlands), say their findings suggest that the role of ECGs in existing cardiovascular prevention programs should be evaluated.

The patients assessed by the researchers underwent a baseline ECG and examination. Data from clinically recognized MIs (i.e., heart attacks that were formally diagnosed) over the years that followed were analyzed. The 4,187 of the total who had at least one repeat ECG during two rounds of follow-up assessment between 1993-96 and 1997-99, were analyzed for clinically unrecognized MI.

Senior author Dr. Jacqueline Witteman, associate professor of epidemiology, said, “Over our median follow-up time of more than six years, we found an incidence rate of nine heart attacks per 1,000 person-years. There were around 12 heart attacks per 1,000 person-years in men (8.4 recognized and 4.2 unrecognized) and around seven per 1,000 person-years in women (3.1 recognized and 3.6 unrecognized). Additionally, in men as well as in women, there was one sudden death per 1,000 person-years.”

Overall, she said, 43% of the total heart attacks had been clinically unrecognized – one-third of the male heart attacks and more than a half of the female heart attacks.

Witteman said that in each of the age bands between 55 and 80, men had a higher incidence of recognized MIs than women and a similar incidence of unrecognized MIs. This provided the evidence that heart attacks are less often recognized in women, she said, irrespective of characteristics that have previously been associated with MI.

Report assesses arterial ‘stiffness’ testing

A research team at the Mayo Clinic (Rochester, Minnesota) used a noninvasive tool, called an arterial tonometer, to discover an association between stiffness in arteries and the presence and amount of coronary artery calcium, which the clinic said could lead to the accurate assessment of heart disease risk in adults with no symptoms. Iftikhar Kullo, MD, of the Mayo Clinic and lead author of the study, said that the test is for people determined to be at intermediate risk based on risk factors outlined by the guidelines published by the National Cholesterol Education Project and assessed a score based on the Framingham Risk Score.

“About 40% of the American public is considered to be at moderate risk for heart disease,” said Kullo in a statement. “Nearly half the heart attacks come without warning, which means we need to do a better job of screening people. This test has that potential.”

The study was published in Hypertension, a publication of the American Heart Association (AHA; Dallas). The test, which is called aortic pulse wave velocity (aPWV), measures how fast the pulse wave travels down the aorta, or the major artery arising from the heart. Mayo said it is a potential screening tool because it is quick, taking only 10 to 15 minutes, painless and likely to be less expensive compared with other cardiac screening tests. In use, he patient lies on a bed and a tonometer is placed on the skin over the carotid artery in the neck and then the femoral artery, which is located in the upper thigh. The tonometer measures the pressure wave inside the artery, and the information is fed into a computer for calculation of aPWV.

Kullo said a slower pulse means the artery is more elastic and healthier, while a faster wave means the artery is stiffer and less healthy. “If you have an electrocardiogram running [simultaneously] . . . then you can tell from when the heart pumps blood [where] it is at a particular phase in the electrocardiogram when the actual pressure wave reaches a particular artery,” Kullo told Cardiovascular Device Update. To get a measurement, one measures the onset of the time of the blood in the heart to cycle to the waveform, he said.

“So if you subtract that time delay, that’s the time portion of this equation, and then the distance is simply measured by a measuring tape from the heart to the groin; [and] then we have time, we have distance, so we calculate the velocity, and that’s the aortic pulse wave velocity,” Kullo said.

Researchers tested 401 patients, including 213 men and 188 women, between the ages of 32 and 84 – none of whom had a history of heart attack or stroke – for the research conducted between 2002 and 2004. The median age was 60. The study used a device called the SphygmoCor System by AtCor (West Ryde, Australia).

The research found that study participants with stiffer arteries had a greater amount of calcium in the coronary arteries, an indicator of atherosclerosis. “Previous research showed an APWV predicts cardiovascular disease in older adults, but the association of aPWV and the amount of coronary artery calcium (CAC) in the general population had been “unknown,” Kullo said. Kullo also said the association between artery stiffness and CAC “strengthens the case for using aPWV as a screening tool,” such as in adults with moderate risk, those with a family history of heart disease, patients with high blood pressure and those with kidney disease.

‘Gum inflammation’ a cardio risk

New research is reinforcing the longstanding belief that a connection exists between periodontal disease, or severe gum inflammation, and cardiovascular disease. According to Moise Desvarieux, MD, PhD, infectious disease epidemiologist in the department of epidemiology at the Mailman School of Public Health, Columbia University (New York), the precise relationship is unclear and patients cannot rely only on good oral hygiene as a way to reduce their risk for heart disease. They must manage other risk factors for the disease as well.

“It appears a relationship exists, but we don’t know exactly what it is, and if it is a causal relationship. Therefore, we can’t make recommendations for people with periodontal disease in respect to cardiovascular disease,” said Desvarieux, whose team studies periodontal disease in relation to atherosclerosis, or hardening of the arteries. “To reduce their risk for cardiovascular disease, patients must manage all their risk factors, including smoking, diabetes and weight.”

Desvarieux, who coordinates the INVEST study in Manhattan funded by the National Institutes of Health, as well as the international network investigating the oral health/cardiovascular disease relationship, spoke at a media briefing in New York on “Oral and Systemic Health: Exploring the Connection,” sponsored by the American Medical Association and American Dental Association.

“Our research brings in the microbiological factors that may connect the two diseases,” he said. “We analyzed bacterial samples from the oral cavity, three of which are specifically associated with periodontal disease. We found that those patients with one or any combination of these three bacteria also had atherosclerosis.”

Desvarieux hypothesizes that the atherosclerosis may be a result of bacteria from gum infection entering the bloodstream, creating inflammation in other parts of the body. However, he cautions, “Because both pieces of the puzzle were being measured simultaneously, we don’t know which came first and we can’t say whether the relationship is causal.”