Cardiovascular disease (CVD) is the leading cause of death for women in the United States, killing nearly 500,000 in 2002.1 For women who die of sudden cardiac death, 64% had no previous symptoms. Within 6 years of having a recognized myocardial infarction, 46% of women will be disabled with heart failure and 35% will have another myocardial infarction.1 Since 1984, the number of deaths related to CVD for females has exceeded those for males and continues to rise.1 Research has identified gender differences in the recognition, diagnosis, treatment, and outcomes for patients with CVD.2 Despite these significant findings, adherence to practice guidelines has been suboptimal and female mortality rates have not been impacted.3 Appropriate risk assessment and preventive care are necessary to improve these statistics.
Dyslipidemia is a modifiable risk factor that has a substantial impact on the outcomes of patients with CVD, especially women. By decreasing total cholesterol levels by 10%, there may be an estimated 30% decrease in the incidence of coronary heart disease.1 Recent research has shown that women are less likely than men with similar CVD risk to achieve optimum cholesterol levels.4 This article discusses gender differences in the detection and management of dyslipidemia. By identifying the suboptimal recognition and treatment of lipid abnormalities in women, healthcare professionals can revise their practice patterns in an effort to improve the outcomes for women with CVD.
Current Recommendations for Prevention
A defining moment for women and heart disease occurred in 1999 when Mosca et al published the first evidence-based guidelines for the prevention of CVD in women.5 In 2004, these guidelines were updated to include risk assessment of women.6 The researchers describe the continuum of CVD risk as calculated by the Framingham 10-year coronary heart disease risk score. Those women with less than 10% risk are categorized as low risk, 10% to 20% are deemed intermediate risk, and greater than 20% are identified as high risk (see Table 1).6 By identifying the category of CVD risk, healthcare providers can determine the intensity of intervention.
The clinical recommendations of the researchers include lifestyle and risk factor interventions. The recommendations are classified from class I (useful and effective) to class III (not useful, may be harmful). Supportive evidence ranks as "A" (sufficient evidence from multiple trials), "B" (limited evidence from single randomized trial), or "C" (based on expert opinion or case studies). In regard to lipid management, there were four class I recommendations offered (see Table 2). First, optimal levels of low-density lipoprotein cholesterol (LDL-C) for women are less than 100 mg/dL, with a high-density lipoprotein cholesterol (HDL-C) greater than 50 mg/dL and triglycerides less than 150 mg/dL.6 Second, women of high risk or with LDL-C greater than 100 mg/dL should limit saturated fat intake to less than 7% of total energy per day and cholesterol to less than 200 mg per day in addition to limiting trans-fatty acid intake. Third, pharmacologic treatment should be initiated along with lifestyle therapy in high-risk women with LDL-C greater than or equal to 100 mg/dL and in high-risk women with LDL-C less than 100 mg/dL, unless contraindicated. Finally, for women of intermediate risk, pharmacologic therapy should be initiated if LDL-C is greater than or equal to 130 mg/dL with lifestyle modifications. Also, if HDL-C is low, niacin or fibrate therapy should be considered. In lower-risk women, the class IIa, level B recommendation is to consider pharmacotherapy when the LDL-C is greater than or equal to 190 mg/dL or greater than 160 mg/dL with multiple risk factors.6
Since the publication of these recommendations, the National Cholesterol Education Program (NCEP) released an update to their 2001 guidelines (seeTable 3). In high-risk patients, the LDL-C goal remains less than 100 mg/dL.7 If a patient is very high risk with established CVD plus multiple major risk factors (severe and poorly controlled risk factors, metabolic syndrome, or acute coronary syndrome), the revised goal is LDL-C less than 70 mg/dL. For moderately high-risk patients, an LDL-C goal less than 100 mg/dL is recommended. If lipid-lowering therapy is started for high-risk or moderately high-risk patients, the researchers recommend a 30% to 40% decrease in LDL-C. Also, therapeutic lifestyle changes are suggested for all risk categories. Low-risk patients continue to have an LDL-C goal of 160 mg/dL as defined in the Adult Treatment Panel III.8 These national guidelines provide healthcare professionals with concise goals of lipid management.
Review of Gender Differences
The presence of gender differences in lipid management has been demonstrated in several clinical trials. In 1997, the Heart and Estrogen/Progestin Replacement Study identified the inadequate lipid management of women. A total of 2,763 postmenopausal women with coronary heart disease participated. Over 90% of enrolled women had LDL-C levels greater than target levels of 100 mg/dL. In addition, less than half of these women (47%) were taking lipid-lowering therapy.9
The correlation between achieving LDL-C goals and improved outcomes was demonstrated by the Cholesterol and Recurrent Events trial in 1998.10 The researchers evaluated the effectiveness of pravastatin therapy on 576 postmenopausal women with average cholesterol levels after a myocardial infarction. Women treated with pravastatin therapy had a substantial reduction of all cardiovascular events, with fatal or nonfatal myocardial infarction being reduced by 56%. Male participants in the trial also showed risk reduction, but to a lesser extent than women, despite having significantly less risk factors than the women.
In 2000, Miller et al studied the efficacy of lipid-lowering therapy in patients with preexisting coronary artery disease at centers in the United States and Canada. Although only 20% of the participants were women, there was a significant lower treatment rate for women. At the end of the 3-year trial, only 12% of women had been treated and attained NCEP goals for LDL-C.11 The researchers suggested that the delay in risk stratification of women may be an important determinant of the higher mortality rates in women.
The Lipid Treatment Assessment Project in 2000 evaluated 4,888 dyslipidemic patients on lipid-lowering therapy to determine if goal LDL-C was achieved. The researchers determined that only 38% of the participants reached the LDL-C target as determined by the NCEP.4 Gender was identified as a variable significantly related to achieving the LDL-C goal.
With growing evidence of gender difference in screening and detection of dyslipidemia, the Women's Atorvastatin Trial on Cholesterol trial sought to determine the effectiveness of lipid-lowering therapy in achieving LDL-C goals.12 With the maximal titration of 80 mg of atorvastatin, 80% of women with established CVD were successful in reaching target LDL-C. Despite the fact that HDL-C levels less than 35 mg/dL are a major risk factor for CVD, the researchers identified that 15% of women with HDL-C greater than 60 mg/dL had clinically evident CVD. This emphasizes that CVD risk should not be underestimated in women with normal or high levels of HDL-C in addition to high LDL-C.12
Most recently, in 2005, Mosca et al evaluated the lipid management and treatment patterns based on the evidenced-based guidelines for CVD prevention in women. Of the 8,353 high-risk women included in the study, only 12% reached LDL-C goals after 3 years of follow-up. Pharmacologic therapy was initiated in 35% of women with LDL-C greater than 100 mg/dL. In these women, the mean time between laboratory results and date of first prescription was 8± 9 months. Only 11% of women with HDL-C less than 50 mg/dL and/or a non-HDL-C greater than 130 mg/dL were prescribed niacin or fibrate therapy. The overall success in attaining combined targets for LDL-C, HDL-C, and triglycerides was 12% at 36 months. This research further emphasizes the need to reevaluate practice patterns to adhere to national guidelines and improve outcomes for women.13
Wexler and colleagues analyzed the gender differences in the treatment of coronary heart disease risk in diabetic patients. The researchers showed gender bias with women being less likely to be pharmacologically treated with lipid-lowering medication and less likely to attain goal LDL-C levels when treated.14 As with previous studies and despite increased awareness of risk and treatment guidelines to the medical profession, these recent studies show that women continue to have suboptimal care.
Implications for Practice
Whether in an outpatient or inpatient setting, healthcare providers are obligated to improve the management of dyslipidemia for women. Kim et al discuss several provider factors that contribute to suboptimal screening and treatment of dyslipidemia.15 Inappropriate perception of CVD risk is one factor that has significant impact on lipid management.
Proper identification of CVD risk is vital to the prevention and treatment of hyperlipidemia. Mosca et al surveyed 500 physicians to evaluate adherence to current CVD prevention guidelines. The researchers found that despite similar risk profiles, men were more likely than women to be assigned to a higher risk category by physicians. By being assigned a lower risk category, women were less likely to be counseled on diet, physical activity, and supplemental therapy.3
The importance of educational efforts of healthcare workers is evident in the research. Mosca et al found that of the 500 physicians participating in the research, only 8% of primary care physicians, 13% of obstetrical physicians, and 17% of cardiologists were aware that more women die each year of heart disease than men.3 Educational efforts must be targeted at nurses, physicians, advanced practice providers, medical schools, and nursing schools. The American Heart Association has launched its "Go Red for Women" campaign to increase awareness of women and heart disease.16 Providers must continue to be educated on current guidelines and practices as well as educating patients of these recommendations.
Future research must continue to address the need to evaluate the effectiveness of and adherence to evidence-based guidelines. Mosca et al suggest future research that focuses on strategies to improve physician and patient adherence to guidelines.3 In addition, major clinical trials must include representation of women to reduce bias and increase clinical relevance for women. Finally, future research should focus on female-specific risk factors. Ridker and associates studied 28,263 postmenopausal women and found that high-sensitivity C-reactive protein was the most significant predictor of cardiovascular events in women. Screening with C-reactive protein identified women as high or low risk, despite normal LDL-C levels.17 Such research must be included as guidelines for CVD prevention in women are revised.
As discussed, adherence to current guidelines is a critical element of dyslipidemia management. It is equally important for providers to recognize the variety of other issues that impact the success of dyslipidemia management in women. Factors such as age, attitude about hyperlipidemia, adverse reactions to medication therapy, and cost of medications may all affect patient compliance.
Research has identified that women of a younger age are less likely to remain compliant with lipid-lowering therapy.18-20 Public education efforts need to target these younger age groups to promote awareness of CVD in women. Foley and colleagues summarized that patient attitudes and beliefs about hyperlipidemia impact patient adherence. The quality of communication between providers and patients and their attitudes about the effectiveness of medications are correlated with medication compliance.21 Kim et al identified adverse reactions as an important factor of medication adherence.18 Many patients are unable to tolerate statin therapy because of the reported myopathy side effects. However, research has shown that the actual incidence of myopathy is less than 0.1% for most statins.22 It is important for providers to choose appropriate lipid-lowering agents at proper dosages in those patients at higher risk for myopathies.23 Finally, the cost of lipid-lowering therapy is a crucial factor in compliance of dyslipidemia management. Schultz et al found that as the mean co-payment of statins increased, the likelihood of compliance decreased.19 For women with no insurance and on a fixed income, the decision to purchase a lipid-lowering medication is often outweighed by the need to obtain the basic necessities of living. Prescriptive assistance is available but time-consuming and cumbersome for patients to complete. There is an obligation of prescription drug manufacturers to reduce medication costs and simplify assistance programs in an effort to improve compliance.
It is important for providers to be aware of these barriers to adherence in order to target specific populations or explore alternative treatments. Providers are not the only solution to improving outcomes for women, but they are the vital link to successful dyslipidemia management and follow-up.
Gender differences in the care of patients with CVD are evident across the continuum from detection and screening through treatment and outcomes. This article specifically focuses on the suboptimal management of dyslipidemia in women. Research has demonstrated significant differences in risk assessment, screening, pharmacologic intervention, lifestyle recommendations, and goal attainment of optimal lipid levels in women. Despite the guidelines for CVD prevention in women along with the NCEP's release of the Adult Treatment Panel III, little, if any, progress has been made in improving the management of dyslipidemia in women. Healthcare providers must be aware of these differences, be educated of current guidelines, be knowledgeable of barriers to compliance, and be aggressive in risk stratification and lipid management for women. Without refining our aim at the target of appropriate lipid levels, we will continue with missed opportunities at improving the outcomes of women with CVD.
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