Appendix A

Clarifications

This appendix describes several conditions that the Committee on Preventive Services for Women examined to determine if there may be gaps in preventive services necessary for women’s health and well-being that are not included in the United States Preventive Services Task Force (USPSTF) Grade A and B recommendations, Bright Futures, and Advisory Committee on Immunization Practices (ACIP) guidelines. The committee conducted a full review of the following conditions and risk factors, including those relating to cardiovascular disease, osteoporosis, breast cancer, mental health, tobacco use, and diet and physical activity. For these conditions, the committee concluded that there was insufficient evidence to develop new recommendations. At the same time, evidence supported by peer-reviewed studies, federal goals, professional clinical guidelines, and existing federal practices led the committee to suggest a clarifying statement to existing USPSTF recommendations, or led to a suggestion that specific services should be addressed within the context of the well-woman preventive care visit recommended by the committee. Several of the committee descriptions that follow serve as examples of areas in which further high-quality research is needed to understand and better address preventive services for women.

CARDIOVASCULAR DISEASE

Cardiovascular disease (CVD) is the class of diseases that involve the heart or blood vessels and includes high blood pressure, coronary heart disease (CHD), stroke, and heart failure (Bonow et al., 2011). Addressing cardiovascular disease across the life span in women, including during



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Appendix A Clarifications This appendix describes several conditions that the Committee on Preventive Services for Women examined to determine if there may be gaps in preventive services necessary for women’s health and well-being that are not included in the United States Preventive Services Task Force (USPSTF) Grade A and B recommendations, Bright Futures, and Advisory Committee on Immunization Practices (ACIP) guidelines. The committee conducted a full review of the following conditions and risk factors, including those re- lating to cardiovascular disease, osteoporosis, breast cancer, mental health, tobacco use, and diet and physical activity. For these conditions, the com- mittee concluded that there was insufficient evidence to develop new recom- mendations. At the same time, evidence supported by peer-reviewed studies, federal goals, professional clinical guidelines, and existing federal practices led the committee to suggest a clarifying statement to existing USPSTF recommendations, or led to a suggestion that specific services should be addressed within the context of the well-woman preventive care visit rec- ommended by the committee. Several of the committee descriptions that follow serve as examples of areas in which further high-quality research is needed to understand and better address preventive services for women. CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) is the class of diseases that involve the heart or blood vessels and includes high blood pressure, coronary heart disease (CHD), stroke, and heart failure (Bonow et al., 2011). Address- ing cardiovascular disease across the life span in women, including during 171

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172 CLINICAL PREVENTIVE SERVICES FOR WOMEN adolescence, the reproductive years, and maturity, is important. It has been shown that risk factors experienced during pregnancy, such as hypertension of pregnancy, gestational diabetes, and preeclampsia, place women at risk for the development of cardiovascular disease as they age. Prevalence/Burden More women die annually from heart disease than men, but overall, men have a higher burden of CVD (Roger et al., 2011). Likely because of the obesity epidemic in the United States, rates of mortality from CHD (CVD affecting the coronary arteries) in women aged 35 to 54 years have increased in recent years. CVD rates for American black females are significantly higher than those for their white counterparts (286.1/100,000 population and 205.7/100,000 population, respectively) (Mosca et al., 2011; Roger et al., 2011). The black female population also has a lower rate of awareness of heart disease than white women (Ferris et al., 2005; Kleindorfer et al., 2009; Mosca et al., 2010; Roger et al., 2011). More women die each year of stroke and stroke constitutes a higher proportion of CVD events in women, compared with a higher proportion of coronary heart disease in men. The majority of the research from which preventive care recommendations are derived is based on CHD and not stroke (Mosca et al., 2011). Evidence shows differences in the pathology of CHD by sex, with women having a higher prevalence of disease of the small coronary vessels than men (Bairey Merz et al., 2006; Jacobs, 2006). Symptoms of CHD are more likely to be atypical, including dyspnea and epigastric discom- fort (Canto et al., 2007). Lastly, premenopausal women who suffer sud- den death are more likely to have pathologic findings of plaque erosion than plaque rupture, which is more common in men and postmenopausal women (Burke et al., 1998; Oparil, 1998). Older women who suffer a myocardial infarction are more likely than men to have plaque rupture with thrombus (Kruk et al., 2007). The relevance of these findings is unclear but points to biological differences in CHD in women, the full extent of which remains unknown. Risk Factors for CVD Most modifiable risk factors for the primary prevention of CVD, such as hypertension, hyperlipidemia, diabetes mellitus, smoking, obesity, meta- bolic syndrome, and physical inactivity, are similar in women and men; but the prevalence and impact of certain risk factors may differ by sex. Risk factors in which there are sex differences in prevalence and impact or in

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173 APPENDIX A which there are different criteria by sex are outlined below. Diabetes mel- litus, obesity, smoking, and physical activity are addressed in other sections of this document. Lipids: Elevated levels of low-density lipoprotein (LDL) present equivalent risks to women and men but a high-density lipoprotein (HDL) level of <50 mg/dL is considered a risk in women and an HDL level of <40 mg/dL is considered a risk in men (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2002; Mosca et al., 2011). Currently, interventions to improve HDL mainly focus on lifestyle and control of traditional risk factors. No sex-specific interventions for increasing HDL levels currently exist. Metabolic Syndrome: Metabolic syndrome is a constellation of risk fac- tors that are associated with the development of CVD and type 2 diabetes mellitus. The diagnosis is made when three of the following five findings are present: (1) elevated waist circumference (≥40 in. [102 cm] in men and ≥35 in. [88 cm] in women), (2) elevated triglyceride levels (≥150 mg/dL [1.7 mmol/L]) or drug treatment for elevated triglyceride levels, (3) reduced HDL cholesterol levels (<40 mg/dL [1.03 mmol/L] in men and <50 mg/dL [1.3 mmol/L] in women or drug treatment for reduced HDL cholesterol levels, (4) elevated blood pressure (≥130 mm Hg systolic blood pressure or ≥85 mm Hg diastolic blood pressure) or antihypertensive drug treatment, and (5) elevated fasting glucose level of ≥100 mg/dL or drug treatment for elevated glucose levels (Grundy et al., 2005). The prevalence of the metabolic syndrome is increasing and varies by age in women and men, with the prevalence being higher in men up to the age of 60 years, after which the rates are higher in women (51.5 percent in men versus 54.4 percent in women) (Ervin, 2009). Importantly, the rates of meta- bolic syndrome are significantly higher in non-Hispanic black and Mexican American women than in their male counterparts (38.8 and 25.3 percent, re- spectively, for non-Hispanic black women versus men and 40.6 and 33.2 per- cent, respectively, for Mexican American women versus men) (Ervin, 2009). Meta-analyses of studies evaluating the metabolic syndrome showed an association of metabolic syndrome with an increased risk of develop- ing CVD and death from CVD (relative risk = 1.78; 95 percent confidence interval = 1.58 to 2.00), with the association between metabolic syndrome and an increased risk of CVD being stronger in women than in men in the smaller number of studies that provide data by sex (relative risk = 2.63 versus 1.98, P = 0.09) (Gami et al., 2007). Women with metabolic syndrome have a three times higher risk of dying from a heart attack or stroke than women who do not have it

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174 CLINICAL PREVENTIVE SERVICES FOR WOMEN (Cleveland Clinic, 2011), and they have a significantly elevated risk for developing type 2 diabetes (Lorenzo et al., 2007). Furthermore, women diagnosed with metabolic syndrome in early pregnancy have a significantly greater risk of developing gestational diabetes mellitus. An accurate mea- surement of the waist circumference must be obtained to make a diagnosis of metabolic syndrome. Pregnancy-Related Risk Factors: Pregnancy-related risk factors such as preeclampsia, gestational hypertension, and gestational diabetes mellitus are specific to women and are risk factors for the development of CVD and CVD events in women as they age. These pregnancy-related disorders are highly prevalent, with approximately 5 percent of pregnancies complicated by preeclampsia. Gestational diabetes, which complicates 5 percent of preg- nancies, is often seen in women who also have gestational hypertension. Women who experience preeclampsia have twice the risk of heart dis- ease, stroke, and venous thromboembolism as they age and are twice as likely to die of cardiovascular disease (Bellamy et al., 2007; McDonald et al., 2008; Rich-Edwards et al., 2010). In a Canadian population, women who have preeclampsia and preterm birth (<37 weeks of gestation) have been found to have an eight-fold higher risk of mortality from CVD than women who do not have preeclampsia and who give birth at term (Irgens et al., 2001). Approximately 50 percent of the women who experience gestational diabetes mellitus will go on to develop type 2 diabetes mellitus and also experience a 70 percent increase in the risk of CVD, much of which can be attributed to the development of type 2 diabetes mellitus (Shah et al., 2008). Black women experience significantly higher rates of these pregnancy com- plications (Rich-Edwards et al., 2010). Little is currently understood about the possible vascular abnormalities caused by these disorders or the time course of the increase in risk. Simi- larly, research on the etiology of these disorders and how best to prevent them before pregnancy, during pregnancy, or between pregnancies is lack- ing. Given the association of preeclampsia, gestational hypertension, and gestational diabetes with an increased risk of CVD in women as they age, the 2011 American Heart Association (AHA) guidelines for prevention of CVD in women recommends that a history of pregnancy complications be obtained as part of the evaluation of CVD risk in women (Mosca et al., 2011).

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175 APPENDIX A Depression: Depression is more common in women than men and dis- proportionately affects the outcomes of women who have experienced a myocardial infarction. Screening for depression is recommended for women with CVD, but no evidence suggests that screening affects the outcomes for these women. Research to understand the role of depression on the development of CVD and how sex and gender influence this relationship is emerging (Mosca et al., 2011). Social Determinants of Health: Evidence shows that the risk for CVD is influenced by social determinants of health, such as socioeconomic status, geographic location, chronic stress, poverty, and racism. The intersection of race/ethnicity, gender, and economic status complicates the understand- ing of who is at risk for metabolic syndrome, but understanding this social patterning is important for the development of targeted interventions. In an analysis of data from the National Health and Nutrition Examination Survey III, economic status was found to have an impact on the incidence of metabolic syndrome for women but not for men. Women in the lowest economic group were more likely to be at risk than women in the highest economic group (Salsberry et al., 2007). Results such as these underscore the potential clinical significance of socioeconomic position, particularly for women (Loucks et al., 2007). Black women are at greater risk for CVD than white women of comparable socioeconomic status, and the age-adjusted rates of death from CVD for black women exceed those for white women (Hayes et al., 2006). Black women in the southern rural United States have among the highest rates of mortality from CVD, especially stroke (Casper et al., 2011). These studies demonstrate that social determinants may have dispro- portionate impacts on the development of CVD in women, but more high- quality evidence is needed in this area. High-Sensitivity C-Reactive Protein: High-sensitivity C-reactive protein is a nonspecific biomarker of increased risk for CVD. The role of the high- sensitivity C-reactive protein levels in the assessment of risk and in defining preventive strategies remains unclear. The Jupiter study, which is often cited as the rationale to use high-sensitivity C-reactive protein for screening, did not include women with low high-sensitivity C-reactive protein levels, and therefore, no definitive statement about the use of this biomarker to screen women in the general population can be made (Mosca et al., 2011; Ridker et al., 2010).

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176 CLINICAL PREVENTIVE SERVICES FOR WOMEN Existing Guidelines and Recommendations USPSTF Recommendations The USPSTF recommends the use of aspirin for women aged 55 to 79 years when the potential benefit of a reduction in ischemic strokes outweighs the poten- tial harm of an increase in gastrointestinal hemorrhage. Grade A recommendation (USPSTF, 2009a). The USPSTF recommends screening for high blood pressure in adults aged 18 and older. Grade A recommendation (USPSTF, 2007a). The USPSTF strongly recommends screening women aged 45 and older for lipid disorders if they are at increased risk for coronary heart disease. Grade A recom- mendation (USPSTF, 2008). The USPSTF recommends screening women aged 20 to 45 for lipid disorders if they are at increased risk for coronary heart disease. Grade B recommendation (USPSTF, 2008). The USPSTF makes no recommendation for or against routine screening for lipid disorders in men aged 20 to 35 or in women aged 20 and older who are not at increased risk for CHD. Grade C recommendation (USPSTF, 2008). The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for lipid disorders in infants, children, adolescents, or young adults (up to age 20). Grade I statement (USPSTF, 2007b). The USPSTF recommends that clinicians ask all adults about tobacco use and provide tobacco cessation interventions for those who use tobacco products. Grade A recommendation (USPSTF, 2009b). The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for tobacco use or interventions to prevent and treat tobacco use and dependence among children or adolescents. Grade I statement (USPSTF, 2003c). Bright Futures recommends screening for high blood pressure through- out adolescence and annual screening for dyslipidemia. Otherwise, Bright Futures provides only anticipatory guidance on this subject (AAP, 2008). Numerous organizations such as the AHA provide a wealth of ex- pansive and specific guidelines for preventing CVD in women. The AHA alone recently published an updated list of more than 20 guidelines. These recommendations are commonly in agreement with those of the USPSTF.

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177 APPENDIX A The Adult Treatment Panel III from the National Cholesterol Education Program recommends that lipids be treated according to the risk stratifica- tion obtained by use of the Framingham risk score. This system stratifies patients into three basic categories by 10-year risk (the percentage prob- ability of experiencing an event in the next 10 years): >20 percent, 10 to 20 percent, and <10 percent. However, these recommendations do not differ by sex. Effective Interventions A large body of evidence has been amassed to support prevention strat- egies for CVD in women and men. Even though CVD-related conditions are often grouped together, most evidence is based on trials that do not include stroke as the primary outcome, which is particularly important, given that stroke is more prevalent in women than men (Mosca et al., 2011). CVD is primarily prevented through adequate treatment of modifiable risk factors, including hypertension, diabetes mellitus, hyperlipidemia, and obesity, and achievement of a healthy lifestyle, including smoking cessation, physical activity, a healthy diet, and maintaining a healthy weight. Metabolic syndrome is a significant risk factor for CVD in women, and the major focus is on preventing or treating the underlying modifi- able risk factors, such as central obesity, hypertension, increased LDL and triglyceride levels, and diabetes mellitus. Lifestyle modification, including weight loss, physical activity, and a healthy diet, decreases all of the meta- bolic risk factors (Grundy et al., 2005). Although good data that link the modification of each risk factor that comprises metabolic syndrome to a decrease in cardiovascular risk are available, the data on preventing or treating metabolic syndrome are lacking. No data directly link screening for metabolic syndrome and prevention of CVD, although the syndrome must be recognized to accurately define women’s risk. Few data are available on effective interventions to prevent the compli- cations of pregnancy, such as gestational hypertension and preeclampsia, which are risk factors for CVD. Achieving a healthy weight before preg- nancy has been linked with decreased rates of these complications (IOM, 2009). Much remains to be learned about the mechanisms underlying these disorders, in particular, preeclampsia. Knowledge of these mechanisms might lead to effective preventive strategies (Rich-Edwards et al., 2010). Finally, identification of these disorders when a woman’s medical history is obtained is important and will help to more accurately define overall risk for CVD.

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178 CLINICAL PREVENTIVE SERVICES FOR WOMEN Identified Gaps The primary gaps in preventive services not already addressed by the provisions set forth in the ACA are (1) there is no comprehensive mecha- nism for the prevention or screening of metabolic syndrome in all women, and (2) there is no comprehensive mechanism in place to collect pregnancy complication histories to better predict the risk level of a woman for devel- oping cardiovascular disease in the future. The committee found insufficient evidence to support a new recom- mendation; instead, evidence supported by professional clinical guidelines led to committee support for the reasonableness of including screening for metabolic syndrome in women and obtaining a history of pregnancy com- plications within the context of the well-woman preventive visit. BONE/SKELETAL DISEASE The USPSTF recommends screening for osteoporosis using bone densi- tometry testing for women aged 65 years and older and in younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors (USPSTF Grade B recommenda- tion). This recommendation was based on the age and personal risk factors of average-risk women with no previous fragility fractures and does not explicitly address women with secondary causes of osteoporosis or previous fractures (USPSTF, 2011d). Osteoporosis is a systemic skeletal condition associated with aging that is characterized by low bone density and deterioration of bone tissue that weakens bones and leads to fractures (USDHS, 2004). Osteoporosis- related fragility fractures result from forces that would not normally cause fractures, such as hip or wrist fractures from falling from standing height or a spine fracture resulting from compression of the vertebra from grav- ity alone. Although some types of fractures are more commonly related to osteoporosis (e.g., spine, hip, and wrist fractures), osteoporotic fractures can occur at nearly all sites. In the absence of a fracture, osteoporosis can also be diagnosed by measuring bone density, or the thickness of bone. Results are expressed as the T-score, which is the difference between an individual’s bone den- sity measurement and normal values. The World Health Organization developed definitions for levels of bone density based on T-scores (Kanis, 1994). T-scores identify only one aspect of the condition, however. Other important components, such as rate of bone loss and quality of bone, are not currently measured in clinical practice. Women with previous osteoporosis-related fractures are at high risk

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179 APPENDIX A for subsequent fractures. Although most women can accurately recall hav- ing had a previous fracture that required medical attention and fractures are usually well documented in medical records, tracking of women for follow-up care is usually difficult. As a result, evaluations for osteoporosis are often missed, drug treatments are not prescribed, and rates of subse- quent fractures are high. Fractures that do not require immediate medical attention are often not recognized, such as spine fractures with mild or no symptoms. Nonetheless, asymptomatic spine fractures are also important in establishing the diagnosis of osteoporosis and determining needs for drug therapy. Osteoporosis may occur without a known cause (primary osteoporo- sis) or occur as the result of another condition (secondary osteoporosis). Common secondary causes include dietary deficiencies in calcium or vitamin D; use of certain medications (aluminum antacids, anticoagulants, anticonvulsants, aromatize inhibitors, barbiturates, cancer chemotherapeutic drugs, depo-medroxyprogesterone, glucocorticoids, gonadotropin-releasing hormone agonists, lithium, and others); and the presence of health condi- tions (rheumatoid arthritis, diabetes, hyperparathyroidism, gastric bypass and other gastrointestinal surgery, malabsorption, inflammatory bowel disease, hemophilia, lupus, rheumatoid arthritis, kidney disease, depression, multiple sclerosis, emphysema, and others). Several additional risk factors for osteoporosis and fractures have been determined from large population studies. Risk factors that cannot be mod- ified include age, menopause, low body mass index, and a family history of osteoporosis and fractures. Modifiable risk factors include immobility, falls, tobacco use, and excessive alcohol intake (three or more drinks daily). Prevalence/Burden Low bone density, osteoporosis, and related fragility fractures are com- mon in older adults. Estimates indicate that as many as 50 percent of Americans over age 50 years, or 14 million individuals by 2020, will be at risk for osteoporotic fractures during their lifetimes (USDHS, 2004). Fracture rates are higher and ages of incidence are younger for women than for men. Rates are highest in whites than in other racial groups, although osteoporosis is common in all groups (George et al., 2003; Looker et al., 1997; Nelson et al., 1995). Older individuals have much higher fracture rates than younger individuals with the same bone density because of in- creasing risks from other important contributors, such as falling (Heaney, 1998). All types of fractures are associated with higher rates of death (Bliuc et al., 2009; Center et al., 1999; Leibson et al., 2002). Nonfatal fractures at any site can impair function and quality of life, cause chronic pain and

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180 CLINICAL PREVENTIVE SERVICES FOR WOMEN disability, and result in high costs for health care and lost productivity (HHS, 2004). Bone densitometry measures the mass of bone and can be used to pre- dict the risk of future fractures, although it is an imperfect measure. Among bone measurement tests at various sites, the result of dual-energy X-ray absorptiometry (DXA) of the hip is the strongest predictor of hip fracture (Marshall et al., 1996). Several peripheral bone measurement tests have also been developed, including quantitative ultrasound (QUS) of the calcaneus (heel), which can predict fractures, as well as DXA, although variation exists across studies (Nelson et al., 2010b). QUS measures bone qualities differently from DXA, and correlates only modestly. Therefore, it is not clear how the results of QUS can be used clinically to select individuals who should receive drug therapies that were proven effective in clinical trials on the basis of DXA criteria. Measurement of the bone density of appropriate candidates is essential before initiation of drug therapy because all of the drugs approved by the Food and Drug Administration (FDA) to treat low bone density and osteo- porosis work by increasing bone density. Obtaining a bone density measure before therapy also provides an opportunity to monitor a response to the drug, if needed. Identification of secondary causes and modifiable risk factors can lead to decisions to treat the underlying cause or risk factor specifically; to moni- tor bone density and treat osteoporosis if bone density is low or a fracture occurs; or to treat osteoporosis, in addition to the secondary cause or risk factor. Actual management depends on the secondary cause or risk factor, the severity of osteoporosis, additional health considerations, and patient preferences. Existing Guidelines and Recommendations USPSTF Recommendations The USPSTF recommends screening for osteoporosis in women aged 65 years or older and in younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors. Grade B recommendation (USPSTF, 2011c). Clinical guidelines from the National Osteoporosis Foundation recom- mend bone density testing for individuals with osteoporosis-related fractures

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181 APPENDIX A or secondary causes of osteoporosis, all women aged 65 years and older, and younger postmenopausal women with key risk factors (NOF, 2010). Despite the increased awareness of osteoporosis and recommenda- tions for screening and treatment from multiple groups, osteoporosis is underdetected and inappropriately treated in the United States (Kiebzak, 2002; Wilkins and Goldfeder, 2004). The reasons for this are unclear, although the different recommendations for identifying candidates for test- ing and treatment and confusion in interpreting the results of testing may be contributors (Morris et al., 2004). In addition, current medical practice in the United States is commonly fragmented for individuals experiencing osteoporosis-related fractures. The fracture itself is usually treated by an acute care team in hospital emergency departments and orthopedic ser- vices, whereas screening, prevention, and treatment are addressed in other contexts. Effective Interventions Primary prevention of osteoporosis and fractures begins early in life, while bone undergoes development. Attainment of peak bone mass and its maintenance require optimal nutrition and physical activity throughout the life span and avoidance of tobacco, alcohol, and other exposures that contribute to osteoporosis. All women require adequate calcium (1,200 mg daily) and vitamin D (800 to 1,000 international units daily) intake to avoid deficiencies and prevent osteoporosis and fractures (Standing Committee, 1997). Those with secondary causes of osteoporosis may require treatment of their specific underlying conditions to reduce their risks for osteoporosis and fractures. Women using medications causing osteoporosis may require adjustments in their medications and serial measures of bone densitometry to monitor effects on their bones. The FDA has approved several drugs for prevention or treatment of osteoporosis (FDA, 2011) that reduce the risk for osteoporosis-related fractures by increasing bone density. Women with the lowest levels of bone density or with previous osteoporosis-related fractures are the most likely to benefit (Cummings et al., 1998). These drugs differ by their mechanisms of action, effectiveness in reducing fractures, routes of administration, and adverse effects. Drugs for prevention are intended for individuals who have no previ- ous fractures and whose bone density levels are not in the osteoporotic range (i.e., T-score ≥–2.5). For women, these include four bisphosphonate drugs, alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel, Actonel with calcium), and zoledronic acid (Reclast); several forms of estrogen with or without a progestin hormone; and raloxifene (Evista). For

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207 APPENDIX A Gail, M. H., L. A. Brinton, D. P. Byar, D. K. Corle, S. B. Green, C. Schairer, and J. J. Mulvihill. 1989. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. Journal of the National Cancer Institute 81(24):1879–1886. Gami, A. S., B. J. Witt, D. E. Howard, P. J. Erwin, L. A. Gami, V. K. Somers, and V. M. Montori. 2007. Metabolic syndrome and risk of incident cardiovascular events and death: A systematic review and meta-analysis of longitudinal studies. Journal of the American College of Cardiology 49(4):403–414. Garber, J. E., and K. Offit. 2005. Hereditary cancer predisposition syndromes. Journal of Clinical Oncology 23:276–292. Garrett, B. E., S. R. Dube, A. Trosclair, R. S. Caraballo, T. F. Pechacek, National Cen- ter for Chronic Disease Prevention and Health Promotion, CDC. 2011. Cigarette smoking—United States, 1965-2008. MMWR Morbidity and Mortality Weekly Report 60 (1):109–113. Gaynes, B. N., S. L. West, C. Ford, P. Frame, J. D. Klein, and K. N. Lohr. 2004. Screening for suicide risk: A systematic evidence review for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality. George, A., J. K. Tracy, W. A. Meyer, R. H. Flores, P. D. Wilson, and M. C. Hochberg. 2003. Racial differences in bone mineral density in older men. Journal of Bone Mineral Re- search 18(12):2238–2244. Gostin, L. O., P. S. Arno, and A. M. Brandt. 1997. FDA regulation of tobacco advertising and youth smoking—historical, social, and constitutional perspectives. Journal of the American Medical Association 277(5):410–418. Grimshaw, G. M., and A. Stanton. 2006. Tobacco cessation interventions for young people. Cochrane Database of Systematic Reviews (4):1–58. Grundy, S. M., J. I. Cleeman, S. R. Daniels, K. A. Donato, R. H. Eckel, B. A. Franklin, D. J. Gordon, R. M. Krauss, P. J. Savage, S. C. Smith, Jr., J. A. Spertus, and F. Costa. 2005. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112(17):2735–2752. Gui, G. P., R. K. Hogben, G. Walsh, R. A’Hern, and R. Eeles. 2001. The incidence of breast can- cer from screening women according to predicted family history risk: Does annual clinical examination add to mammography? European Journal of Cancer 37(13):1668–1673. Hayes, D. K., C. H. Denny, N. L. Keenan, J. B. Croft, A. A. Sundaram, and K. J. Greenlund. 2006. Racial/ethnic and socioeconomic differences in multiple risk factors for heart dis- ease and stroke in women: Behavioral Risk Factor Surveillance System, 2003. Journal of Women’s Health (Larchmont) 15(9):1000–1008. Heaney, R. P. 1998. Bone mass, bone loss and osteoporosis prophylaxis. Annals of Internal Medicine 128:313–314. Henriksson, M. M., H. M. Aro, M. J. Marttunen, M. E. Heikkinen, E. T. Isometsa, K. I. Kuoppasalmi, and J. K. Lonnqvist. 1993. Mental-disorders and comorbidity in suicide. American Journal of Psychiatry 150(6):935–940. HHS (U.S. Department of Health and Human Services). 1999. The Surgeon General’s call to action to prevent suicide. Washington, DC: U.S. Public Health Service. HHS. 2001. Women and smoking: A report of the Surgeon General. Washington, DC: U.S. Department of Health and Human Services. HHS. 2004. Bone health and osteoporosis: A report of the Surgeon General. Washington, DC: Office of the Surgeon General, U.S. Public Health Service, U.S. Department of Health and Human Services.

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