CME

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JUNE 2009

Cardiovascular Disease in Women, Part 1: Identification of Women at Risk

Catherine J. McNeal, MD, PhD; Jessica Birchem, DO

Continuing Medical Education

Release date: June 2009. Termination date: June 2010. Estimated time to complete this activity: 1 hour. GOAL To describe a comprehensive approach to identifying cardiovascular disease (CVD) and diagnosing CVD in women. INTENDED AUDIENCE This CME Activity is designed for ObGyns, primary care physicians, and nurse practitioners. LEARNING OBJECTIVES To identify women at risk for CVD by using risk-scoring systems. To contrast CVD diagnosis in women versus men. To evaluate the risks of CVD in special situations (eg, pregnancy and menopause). ACCREDITATION This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Albert Einstein College of Medicine and Quadrant HealthCom Inc. Albert Einstein College of Medicine is accredited by the ACCME to provide continuing medical education for physicians. Albert Einstein College of Medicine designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity. This activity has been peer reviewed and approved by Brian Cohen, MD, Professor of Clinical ObGyn, Albert Einstein College of Medicine. Review date: April 2009. Participants who answer 70% or more of the questions correctly will obtain credit. To earn credit, see the instructions on page 47 and mail your answers according to the instructions on page 48. CONFLICT OF INTEREST STATEMENT The “Conflict of Interest Disclosure Policy” of Albert Einstein College of Medicine requires that authors participating in any CME activity disclose to the audience any relationship(s) with a pharmaceutical or equipment company. Any author whose disclosed relationships prove to create a conflict of interest, with regard to their contribution to the activity, will not be permitted to publish. The Albert Einstein College of Medicine also requires that faculty participating in any CME activity disclose to the audience when discussing any unlabeled or investigational use of any commercial product, or device, not yet approved for use in the United States. The authors report no conflict of interest and no discussion of off-label use. Dr Cohen reports no conflict of interest. The staffs of CCME of Albert Einstein College of Medicine and The Female Patient have no conflicts of interest with commercial interest related directly or indirectly to this educational activity.

In the United States, the number of deaths in women attributable to cardiovascular disease (CVD) is greater than the combined next 7 leading causes.1 While several large studies and a number of clinical practice guidelines have increased our knowledge and resulted in more effective diagnosis and treatment of CVD in the female patient, more emphasis needs to be placed on this critical disease.2-7

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Identification of Women At Risk for CVD

The American Heart Association (AHA) guidelines for stratifying CVD risk in women (Table 1) are based on identification of any major risk factor (Table 2) and a knowledge of the Framingham Risk Score (FRS) to help guide therapy.8 Age, smoking status, blood pressure, total cholesterol, and high-density lipoprotein (HDL) cholesterol are needed to calculate the FRS, which is an estimate of the risk of “hard” coronary heart disease (CHD) endpoints (myocardial infarction [MI], death from CHD) over a 10-year projection.9,10

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TABLE 1. CVD Risk Categories for Women

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TABLE 2. Defining Values of Major Risk Factors

There are multiple concerns about the utility of the FRS in women, including the fact that it does not reflect the risk for developing “soft” endpoints that are more common in women such as stroke, angina, or need for coronary revascularization. The 10-year risk projection in the FRS may also underestimate a woman’s risk for developing CHD since women tend to live longer than men, resulting in an increased lifetime risk even if 1 risk factor is left untreated. The FRS has also been criticized because it omits family history as a predictive factor, which increases a woman’s risk for CHD 2.3-fold. Finally, the FRS only predicts CHD events, but total CVD risk is more important given that other forms of atherosclerotic disease (stroke) predominate in women.11

To address these concerns, the Reynolds Risk Score (RRS)(www.reynoldsriskscore.org) has recently been introduced and may be a superior indicator of CVD risk, especially in postmenopausal women.12 This score combines the same risk factors as the FRS, but also includes family history, glycosylated hemoglobin value, and high sensitivity C-Reactive Protein (hsC-RP) levels (a biomarker associated with subclinical inflammation). Measurement of hsC-RP levels is gaining increasing attention as an additional part of the risk assessment. Many conditions (infections, allergies, inflammatory diseases) can elevate hsC-RP values for weeks; care must be exercised when ordering this test and in the interpretation if hsC-RP is elevated.

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Identification of Women with Undiagnosed Cerebral Vascular Disease and Peripheral Arterial Disease

Up to 20% of women do not exhibit classic angina but may instead complain of nonspecific symptoms that are often missed or ignored (see www.femalepatient.com, eTables 1 and 2, for conditions encompassed by CVD and CVD signs and symptoms).13 Stroke and transient ischemic event symptoms can also differ (see www.stroke.org for more information). Women are also more likely than men to have peripheral arterial disease (PAD) without experiencing the classic symptoms of intermittent claudication. Because atherosclerosis is common to CHD, carotid artery disease, and PAD, the health care professional should screen for other forms of atherosclerosis (and CVD risk factors) if one variant of CVD is present.

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eTABLE 1. What Does Cardiovascular Disease Encompass?

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eTABLE 2. Identification of Women With Undiagnosed CVD: Signs and Symptoms

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DIAGNOSIS OF CHD

Diagnosis of CHD in women is challenging. Women have less typical anginal symptoms, higher false-positive test rates, and decreased diagnostic accuracy with noninvasive imaging. This makes diagnosis difficult and necessitates a high index of suspicion by the health care professional. Compared to men, women have a different coronary artery anatomy (smaller vessels), are more likely to have single-vessel disease, and less coronary artery luminal obstruction.14 Up to 10% of women with minimal or no disease by coronary angiography (ie, those with “a normal angiogram”) who have chest pain will experience myocardial infarction (MI) within 4 years. In more than 80% of such women with a “normal” angiogram there is evidence of significant atherosclerotic plaque by intravascular ultrasound.15 Thus, there is a significant atherosclerotic plaque burden within the arterial wall, but it does not intrude on the coronary artery lumen.

Stress Testing

There are many different noninvasive tests (exercise electrocardiogram [ECG], stress echocardiography, nuclear perfusion studies, etc.) with gender-specific considerations that impact optimal testing modality selection and interpretation. Calculating the risk of CHD from standardized risk scores (FRS and RRS) helps to choose the next step in the evaluation. In asymptomatic women with a low pretest risk for CHD, the goal is prevention through maximal risk factor reduction. Because women are more likely to have false-positive tests, exercise ECG testing is less predictive in women compared to men. This is likely due to the lower pretest probability, the fact that women are less likely to achieve an adequate heart rate with exercise, and have more frequent resting ECG changes.14,16 Despite these concerns, this test remains the optimal initial test for symptomatic women with a normal baseline ECG who are capable of exercise. Imaging (echocardiography or nuclear perfusion studies) increases the sensitivity and specificity for detecting coronary artery disease. Pharmacologic stress (dobutamine, dipyridamole) is suggested for patients with an abnormal baseline ECG and/or those who cannot exercise or are unlikely to reach a targeted heart rate with exercise. For symptomatic women with an intermediate to high pretest likelihood of CHD, imaging is recommended over the exercise EKG in women.14

Noninvasive Imaging

Newer noninvasive imaging modalities to aid risk stratification of asymptomatic women are now available, including computed tomography for coronary artery calcium (CAC) scoring with or without computerized tomography angiography (CTA), cardiac magnetic resonance imaging (MRI), and carotid intima-media thickness. CAC scores are traditionally lower in women. They have a very high negative predictive value, but, if positive, CAC does provide “independent incremental information that can be applied to the traditional risk factors.”17 However, CAC testing is not currently routinely recommended to evaluate women at risk for CVD. Cardiac MRI and carotid intima-media thickness testing have been used as noninvasive tests to evaluate women at risk and with CVD, but are relatively new and there is a paucity of outcomes data in women, so none are routinely recommended.14

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Special Situations and Opportunities

Pregnancy

Low birth weight may be a harbinger of future cardiovascular disease. Multiple epidemiological studies suggest that infants born small-for-gestational age have an increased risk of developing premature CVD as adults because of intrauterine factors that affect the expression of many genes, especially those related to obesity and insulin resistance.18 It is important that such infants are identified and that their higher CVD risk status is maintained as part of their medical history.

Women with early severe preeclampsia, recurrent preeclampsia, or gestational hypertension are at increased risk of CVD later in life.19 In addition, maternal placental syndromes when combined with other CV risk factors may increase the risk for developing future CVD.20 These diagnoses are also important to maintain and carry forward in a woman’s medical history.

Menopause

Although more women than men die from CVD, this is primarily attributable to loss of the gender advantage with menopause. While the controversy surrounding hormone therapy (HT) is well known, one finding from the Heart and Estrogen/Progestin Replacement Study (HERS) that has largely been ignored is that women with elevated lipoprotein-a (Lp(a)) levels who were in the treatment arm of the study had a markedly decreased risk of CHD compared with the placebo arm.21 Some studies suggest that estrogen decreases Lp(a) levels so it would naturally follow that Lp(a) levels would increase without HT, resulting in an increased level of this risk factor.22 Although routine measurement of Lp(a) levels prior to contemplating HT is not yet advocated, it may be beneficial and provide important information to include in the decision to initiate or stop HT.

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CONCLUSION

The misconception that CVD is a man’s disease must be altered. For women younger than 65 years of age, the mortality rate after MI is twice that for men and the one-year mortality rate is 1.5 times higher. Thus, a “normal” angiogram in symptomatic women should not reduce our concern about their long-term risk for CHD.

NOTE: For additional content related to this article, visit www.femalepatient.com to see eTables, What Does Cardiovascular Disease Encompass? and Identification of Women With Undiagnosed CVD: Signs and Symptoms. Web-only content is not designated for CME credit.

DISCLAIMER
The opinions expressed herein are those of the author and do not necessarily represent the views of the ACCME accredited provider or the publisher. Please review complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings, and adverse effects before administering pharmacologic therapy to patients.

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Catherine J. McNeal, MD, PhD, is Associate Professor of Internal Medicine and Associate Professor of Pediatrics; and Jessica Birchem, DO, is Fellow, Cardiovascular Disease Fellowship Program, both in the Department of Medicine, Division of Cardiology, Scott and White Memorial Hospital and Clinic, Texas A&M University Health Science Center College of Medicine, Temple, TX.

References

1. Heron M. Deaths: Leading causes for 2004. Natl Vital Stat Rep. 2007;56(5):1–95.
2. Mosca L, Manson JE, Sutherland SE, Langer RD, Manolio T, Barrett-Connor E. Cardiovascular disease in women: a statement for healthcare professionals from the American Heart Association. Writing Group. Circulation. 1997;96(7): 2468–2482.
3. Pilote L, Dasgupta K, Guru V, et al. A comprehensive view of sex-specific issues related to cardiovascular disease. CMAJ. 2007;176(6):S1–S44.
4. Christian AH, Rosamond W, White AR, Mosca L. Nine-year trends and racial and ethnic disparities in women’s awareness of heart disease and stroke: an American Heart Association national study. J Womens Health (Larchmt). 2007; 16(1):68–81.
5. Mosca L, Linfante AH, Benjamin EJ, et al. National study of physician awareness and adherence to cardiovascular disease prevention guidelines. Circulation. 2005;111(4): 499–510.
6. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349(6):523–534.
7. Merz CN, Kelsey SF, Pepine CJ, et al. The Women’s Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report. J Am Coll Cardiol. 1999;33(6):1453–1461.
8. Mosca L, Banka CL, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007;115(11):1481–1501.
9. Raupach T, Schäfer K, Konstantinides S, Andreas S. Secondhand smoke as an acute threat for the cardiovascular system: a change in paradigm. Eur Heart J. 2006;27(4): 386–392.
10. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110(2):227–239.
11. Blumenthal RS, Michos ED, Nasir K. Further improvements in CHD risk prediction for women. JAMA. 2007; 297(6):641–643.
12. Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA. 2007;297(6):611–619.
13. DeVon HA, Ryan CJ, Ochs AL, Shapiro M. Symptoms across the continuum of acute coronary syndromes: differences between women and men. Am J Crit Care. 2008; 17(1):14–24.
14. Mieres J, Shaw LJ, Arai A, et al. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: Consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation. 2005; 111(5):682–696.
15. Pepine CJ. Ischemic heart disease in women: facts and wishful thinking. J Am Coll Cardiol. 2004;43(10):1727–1730.
16. Morise AP, Diamond GA. Comparison of the sensitivity and specificity of exercise electrocardiography in biased and unbiased populations of men and women. Am Heart J. 1995;130(4):741–747.
17. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49(18):1860–1870.
18. Godfrey KM, Barker DJ. Fetal nutrition and adult disease. Am J Clin Nutr. 2000;71(5 Suppl.):1344S–1352S.
19. Wilson BJ, Watson MS, Prescott GJ, et al. Hypertensive diseases of pregnancy and risk of hypertension and stroke later in life: results from cohort study. BMJ. 2003; 326(7394):845.
20. Ray JG, Vermeulen MJ, Schull MJ, Redelemeier DA. Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study. Lancet. 2005;366(9499):1797–1803.
21. Shlipak MG, Simon JA, Vittinghoff E, et al. Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause. JAMA. 2000; 283(14):1845–1852.
22. Taskinen MR, Puolakka J, Pyörälä T, et al. Hormone replacement therapy lowers plasma Lp(a) concentrations. Comparison of cyclic transdermal and continuous estrogen-progestin regimens. Arterioscler Thromb Vasc Biol. 1996;16(10):1215–1221.

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