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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Stroke. Author manuscript; available in PMC 2010 April 1.
Published in final edited form as:
PMCID: PMC2753397
NIHMSID: NIHMS132438

Gender differences in presenting and prodromal stroke symptoms

Abstract

Background and Purpose

Prompt recognition of stroke symptoms is critical to timely treatment and women have increased delay to treatment. Women may be more likely to present with atypical symptoms, but this hypothesis has not been extensively evaluated.

Methods

We examined gender differences in the prevalence of presenting and prodromal stroke symptoms among 1,107 consecutive patients hospitalized with neurologist-confirmed acute ischemic stroke. Patient demographics, clinical variables, and stroke symptoms were abstracted from medical records by trained abstractors using standardized forms. Estimates were age standardized to the age distribution of men and women combined. Presenting symptoms occurred within 24 hrs of incident stroke admission, prodromal symptoms occurred ≥ 24 hours of admission

Results

Women were significantly older (p<.001), more likely to have cardioembolic stroke (p<.001) and less likely to receive aspirin (p=.014) or statins (p<0.001). 35% of the sample (n=389) reported prodomal symptoms. Women were more likely to have ≥ 1 somatic prodromal and presenting symptom (p=.03; p=0.008), but did not differ from men on specific somatic symptoms. Women did not differ from men in classic presenting stroke symptoms (p=.89)

Conclusion

Women did not differ significantly in the prevalence of traditional stroke symptoms, but were more likely to have somatic presenting and prodromal symptoms. We found no differences in specific prodromal symptoms, making it difficult to craft a public health message about gender differences in early warning signs of stroke. These results suggest that the focus of stroke prevention education for women should continue to emphasize traditional stroke risk factors.

Keywords: Gender, stroke, symptoms

Stroke is a leading cause of long-term morbidity and disability in the United States and there is a growing awareness of the clinical and public health importance of stroke in women. 1, 2 Although age-specific stroke incidence and mortality rates are higher in men than women, women experience a greater number of strokes per year (60,000) 1 because they live longer and at the oldest age (≥85 years) women have higher mortality rates than men.1 These gender differences in incidence, prevalence, and prognosis of stroke in women will become even more important as the population ages and the proportion of women, particularly older women, increases. 1, 3, 4

In addition to concerns about the increasing prevalence of stroke, women have been shown to be more likely than men to delay seeking treatment for stroke symptoms 5 and to have poorer outcomes after a stroke including disability and poor quality of life. 1, 3, 6 Delay in seeking treatment is a major factor limiting the timely delivery of therapeutic interventions, 6 and prompt, accurate, recognition of stroke symptoms is a critical first step in seeking treatment. 79 In general, public awareness of stroke symptoms is increasing. 10, 11 In one study across 17 states, more people could correctly identify all five symptoms of stroke (52.3%) than could identify all five symptoms of heart attack (24.4%). 10 Despite that, delay to stroke treatment is high and women have been noted to delay three times longer than men. 5

One hypothesis for why women delay longer in seeking treatment is that they may experience different symptoms than men. Gender differences in acute and prodromal symptoms have been reported for MI, 12 but little is known about possible gender differences in stroke symptoms. Despite this lack of evidence however, some public websites have posted information on the “unique symptoms” women experience with stroke and it has become part of the public’s perception of stroke symptoms. 13 If indeed there are gender differences in the symptoms women experience prior to a stroke, this is critical information as a first step in recognizing and appraising the significance of a symptom and seeking prompt treatment. If, however, there are no gender differences, misinformation about unique symptoms may contribute to unnecessary delays in seeking life-saving treatment.

The purpose of this study, therefore, is to examine gender differences in the prevalence of acute and prodromal stroke symptoms.

Subjects and Methods

Data Collection

This study was approved by the Committee on Clinical Investigations at the Beth Israel Deaconess Medical Center. We identified all patients 21 years of age or older admitted to Beth Israel Deaconess Medical Center between April 1, 1999 and December 31, 2004 with a neurologist-confirmed diagnosis of acute ischemic stroke and residing in the Boston metropolitan region. Patient’s medical records were reviewed by trained abstractors to confirm the diagnosis of acute ischemic stroke. Patients with in-hospital strokes or transient ischemic attacks were excluded from further analysis.

For each case, trained abstractors using standardized forms recorded data on patient demographics, past medical history, admission medications, and acute and prodromal symptoms from patient charts or electronic medical records. Race was categorized as White, African American, Asian, other or unknown. Presumed stroke etiology was determined according to an abbreviated TOAST classification system 14 after review of the diagnostic work-up. Acute symptoms were defined as self-reported or witness-reported symptoms occurring within 24 hours of admission to hospital. Prodromal symptoms were defined as self-reported symptoms that preceded the 24 hours of admission to hospital. A neurology nurse practitioner abstracted information on presenting and prodromal symptoms from the admission or discharge note written by the stroke service neurologists. If the patient was aphasic or had a reduced level of consciousness, the family or other witnesses often provided information on prodromal and presenting symptom; or if the patient’s condition improved and they could provide a more complete history, the information was abstracted from the discharge summary. There were not a sufficient number of these patients to assess if the characteristics differed in frequency between men and women.

Statistical Analysis

Descriptive statistics were calculated separately for men and women. We tested the null hypothesis of no difference by gender using a two-sample t-test for continuous variables and Pearson’s Chi-square test of association for categorical variables. Because the age distribution differed between men and women, variables were age-standardized using as the standard the overall age distribution among men and women combined. All hypothesis tests are 2-sided and p<0.05 was considered statistically significant. Analyses were carried out using SAS v9.1.3 (SAS Institute Inc., Cary, NC).

Results

We obtained data on 1107 consecutive patients hospitalized with neurologist-confirmed diagnosis of acute ischemic stroke. Patients were predominantly non-Hispanic white (62.7%) and female (54.9%) with a mean age of 73.0±14.5 years (mean ± SD). Women hospitalized with acute ischemic stroke tended to be older than men, and this difference was statistically significant (women: 75.8±14.5 years; men: 69.7±13.8 years; p<0.0001). No statistically significant between group differences were noted for race or ethnicity (p=0.34). Presumed stroke etiology differed by gender (Table 1). Women were more likely to have cardioembolic stroke or for the mechanism to be undetermined and men were more likely to have large or small vessel stroke. On admission to hospital there were no gender differences in blood pressure for either systolic (women: 159 mmHg±31.7: men 158 mmHg±29.1; p=0.64) or diastolic (women: 79 mmHg±19.5: men: 79 mmHg±15.8; p=0.69) blood pressure.

Table 1
Characteristics of 1107 patients hospitalized for neurologist-confirmed acute ischemic stroke, stratified by Gender.

Table 2 compares the prevalence of co-morbid conditions and admission medications by gender. Women were statistically significantly less likely to have a history of dyslipidemia, diabetes, coronary artery disease, myocardial infarction or to be current smokers. However, after adjusting for age, differences in the prevalence of dyslipidemia and current smoking were only marginally statistically significant. Women were more like than men to have a history of atrial fibrillation, but this difference was not statistically significantly different after age adjustment. Women and men were equally likely have two or more co-morbidities noted on admission (68.7% vs 73.7% respectively, p=0.18).

Table 2
Past medical history and medications on admission among 608 female and 499 male patients hospitalized for acute ischemic stroke, stratified by gender.

On admission, women were statistically significantly less likely than men to be on aspirin or statins, and this difference remained statistically significant after adjusting for age. No statistially significant differences were observed by gender for use of Coumadin, ACE inhibitors, beta blockers, or calcium channel blockers.

The prevalence of specific presenting symptoms did not differ by gender (Table 3). After age-standardization women were as likely as men to report symptoms of: weakness, clumsiness, numbness, seizure, difficulty speaking, difficulty walking, headache, change in behavior, difficulty understanding, nausea, change in vision, feeling “funny”, fatigue, malaise or a variety of non-specific complaints (other). Women and men were also equally likely to report at least one of the classic symptoms that are included in public education about stroke (numbness, weakness, difficulty speaking, change in vision, difficulty walking, headache, clumsiness, or difficulty understanding). However, women were more likely to report at least one non-specific or somatic symptom (p=0.008).

Table 3
Prevalence of presenting symptoms among 608 female and 499 male patients hospitalized for acute ischemic stroke, stratified by gender.

Prodromal symptoms were identified in 35.1% of patients and the prevalence of reported prodromal symptoms did not differ significantly by gender (p=0.64). Women were less likely to report prodromal symptoms of weakness and clumsiness as compared to men, even after age-standardization (Table 1). Numbness was also noted more frequently in men than women, but this difference was not statistically significant in age-standardized estimates. Headache was more commonly reported by women as a prodromal symptom, but this difference was only marginally statistically significant (p=0.051) when age-standardized estimates were considered. When clustered into a single variable, women were more likely to report at least one somatic prodromal symptom.

Discussion

Prior research seeking to understand gender differences in stroke has centered on incidence rates, knowledge of stroke risk factors, clinical presentation, delay to treatment, medical care and outcomes. 2, 5, 6, 15 Although recognition of symptoms is critical to timely treatment, 1, 6, 10, 12,16 and gender-related differences in women’s symptoms with acute myocardial infarction has been observed, 12 little is known about potential differences in stroke symptoms experienced by women. We are aware of only one published study on the prevalence of symptoms among incidence strokes stratified by gender 15 and none that reported on prodromal symptoms.

In this analysis of 1,107 consecutive patients hospitalized for confirmed acute ischemic strokes we found some differences in somatic stroke symptoms for women, but the importance is unclear. Over one third of patients experienced prodromal symptoms, and women were more likely to report having at least one somatic prodromal symptom compared to men. There were no differences between men and women in the prevalence of specific somatic prodromal symptoms, so it is difficult to identify specific symptoms that women should be educated about. Similarly, women were more likely to self-report somatic presenting symptoms, but again there were no statistically significant differences in the specific symptoms reported. Thus, we are not able to identify unique early warning signs of stroke in women. However, it is reassuring to note that more than 97% of both men and women report at least one classic symptom in the twenty-four hours prior to hospital admission.

We did observe that men were more likely to experience the prodrome of weakness, clumsiness and numbness, but after adjusting for age, numbness was not statistically significant. These data are similar to the gender differences noted in the ARIC study where they found that for the most part women did not significantly differ from men in the prevalence of classic symptoms although men were more likely than women to experience gait disturbance (6.7% vs 14.4%; p=0.007). 15 Since these symptoms are included in the classic symptoms disseminated in public health information, the data fit with current practice and do not necessitate any tailoring of the message.

Recommendations from the NIH National Institute of Neurological Disorders and Stroke (NINDS) multidisciplinary working group on Advancing the Study of Stroke in Women, state that research is needed that is focused on gender differences in the perception of risk and prevention for stroke compared with, and independent of, heart disease. 2 They also conclude that there is a need for better education regarding stroke symptoms for women and their care providers. Our data suggest that we should continue to focus on classic or traditional signs and symptoms of stroke for women and perhaps introduce, but not emphasize, less specific, somatic symptoms.

Age standardization added an important dimension to the understanding of presenting and prodromal symptoms. Women who experience stroke tend to be older and some of the co-morbidities and symptoms observed are likely influenced by age. For example, when we adjusted for age, the gender differences noted for the prevalence of atrial fibrillation were attenuated as might be expected since atrial fibrillation is more prevalent in older populations. Other than one symptom (clumsiness) and one prodromal symptom (prodromal numbness) we did not observe material differences in the crude and age-standardized analyses, leading to the conclusion that the gender differences we observed for symptoms were not materially confounded by age; an important consideration as women hospitalized with ischemic strokes tend to be older.

Similar to prior studies 1719 we found that women were less likely than men to be on aspirin or statins at the time of admission even after adjusting for age, This finding is concerning given existing evidence that these treatments might be helpful in preventing stroke in women and the finding in our study that women were more likely to experience cardiembolic stroke.. Several recent studies have demonstrated that aspirin reduced the risk of ischemic stroke in women, but not men, even for those at low risk for cardiovascular disease. 20, 21 Also of interest, inflammation has been associated with the risk of incident and recurrent cardiac events, and probably stroke. 2224 The NINDS working group to advance the study of stroke in women identified the role of various therapies (ie, statins) that have been shown to lower inflammatory markers in women at risk as a priority research area. 2 Thus the finding in the present study that women were less likely to be on Aspirin or statins, could have implications for adequate prevention of stroke in women.

This study has some potentially important limitations. First, the data were obtained through medical record review which presents the potential for misclassification or missing data particularly in regard to presenting and prodromal symptoms. During the time period of the study however, there were a limited number of attending neurologists who reviewed all admission and discharge notes. This increased the consistency and completeness of the notes. Second, early warning or prodromal symptoms were abstracted without knowledge of whether these symptoms appeared or changed in intensity or frequency before the incident stroke and disappeared or returned to previous levels of intensity or frequency afterward. Some have suggested that individuals need time after an incident event to reflect on and accurately identify prodromal symptoms. 12 Finally, our sample was largely white, precluding subanalysis by race or ethnicity and potentially limiting the generalizability of these findings.

Other studies have found a similar distribution of age, co-morbidity and presumed stroke etiology to what we found in the present study. It has been previously noted that women who suffer a stroke tend to be older, and more likely to have atrial fibrillation and hypertension whereas men were more likely to have a history of diabetes, dyslipidemia, tobacco use, cardiovascular disease and myocardial infarction. 3, 2530 In several studies, women have been found to be at increased risk of cardioembolic stroke, likely related to the increased prevalence of atrial fibrillation in older women. 3, 27, 31 Thus, given that the characteristics of our sample are comparable to other published reports, the results of the present study are plausibly generalizable beyond the Boston metropolitan area to other parts of the United States.

In conclusion, after adjusting for age, we did not find evidence that women were less likely then men to experience classic stroke symptoms in the twenty-four hours preceding hospital admission. They were however, more likely to report non-specific or somatic symptoms, although the specific somatic symptoms remain unclear. Some have hypothesized that failure to experience classic stroke symptoms may be one reason that women delay three times longer than men in seeking treatment for acute stroke, but in the present study we did not find this difference in classic symptoms. Others have hypothesized that women were more likely to experience somatic prodromal symptoms and this could lead to confusion and delay in seeking treatment. Although we found that they were more likely to experience at least one somatic symptom, we were not able to identify specific symptoms and the mechanism is unclear and warrants further study. Also of note, we found that women were less likely to receive Aspirin and statins.

Given the retrospective nature of this study, our findings are primarily intended for hypothesis generation. However, until more information is available about the importance of gender differences in somatic symptoms, we suggest that the focus of stroke prevention education for women should continue to emphasize traditional risk factors. Somatic symptoms should be introduced and discussed in conjunction with traditional risk factors, but the message has to be carefully balanced so that women do not fail to recognize traditional stroke symptoms. In addition, providers should be encouraged to adhere to established guidelines for secondary prevention of cardiovascular disease, which recommend Aspirin for women with identified risk factors. 32

Table 4
Prevalence of prodromal symptoms among 210 female and 179 male patients with ≥1 prodromal symptom.

Acknowledgments

None

Funding

We gratefully acknowledge the following grant support; NIH/P01 ES009825-06 (PI Gold/Mittleman), NIH T32 HLO7374-23 (PI Morgan), NIH K99 ES015774 (PI Wellenius), University of Massachusetts Boston Faculty Research Incentive Grant (PI Stuart-Shor). The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NHLBI, or NIH.

Footnotes

Author Disclosures

Eileen M Stuart-Shor: No disclosures

Gregory A Wellenius: No disclosures

Donna Dello Iacono: No disclosures

Murray A Mittleman: No disclosures

Conflicts of Interest Disclosures

None

Contributor Information

Eileen M. Stuart-Shor, University of Massachusetts Boston, Cardiovascular Epidemiology Research Unit, Department of Medicine, Beth Israel, Deaconess Medical Center.

Gregory A. Wellenius, Instructor, Harvard Medical School, Cardiovascular Epidemiology Research Unit, Department of Medicine, Beth Israel, Deaconess Medical Center.

Donna Dello Iacono, University of Massachusetts Boston, Brigham and Woman’s Hospital.

Murray A. Mittleman, Associate Professor Medicine, Harvard Medical School, Associate Professor of Public Health, Harvard School of Public Health, Cardiovascular Epidemiology Research Unit, Department of Medicine, Beth Israel, Deaconess Medical Center.

References

1. American Heart Association. Heart Disease and Stroke Statistics - 2008 Update . http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.187998.
2. Bushnell CD, Hurn P, Colton C, Miller VM, del Zoppo G, Elkind MS, Stern B, Herrington D, Ford-Lynch G, Gorelick P, James A, Brown CM, Choi E, Bray P, Newby LK, Goldstein LB, Simpkins J. Advancing the study of stroke in women: summary and recommendations for future research from an NINDS-Sponsored Multidisciplinary Working Group. Stroke. 2006 Sep;37(9):2387–2399. [PubMed]
3. Reeves MJ, Bushnell CD, Howard G, Gargano JW, Duncan PW, Lynch G, Khatiwoda A, Lisabeth L. Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. Lancet Neurol. 2008 Oct;7(10):915–926. [PMC free article] [PubMed]
4. Carandang R, Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Kannel WB, Wolf PA. Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years. JAMA. 2006 Dec 27;296(24):2939–2946. [PubMed]
5. Mandelzweig L, Goldbourt U, Boyko V, Tanne D. Perceptual, social, and behavioral factors associated with delays in seeking medical care in patients with symptoms of acute stroke. Stroke. 2006 May;37(5):1248–1253. [PubMed]
6. Moser DK, Kimble LP, Alberts MJ, Alonzo A, Croft JB, Dracup K, Evenson KR, Go AS, Hand MM, Kothari RU, Mensah GA, Morris DL, Pancioli AM, Riegel B, Zerwic JJ. Reducing delay in seeking treatment by patients with acute coronary syndrome and stroke: a scientific statement from the American Heart Association Council on cardiovascular nursing and stroke council. Circulation. 2006 Jul 11;114(2):168–182. [PubMed]
7. Williams JE, Rosamond WD, Morris DL. Stroke symptom attribution and time to emergency department arrival: the delay in accessing stroke healthcare study. Acad Emerg Med. 2000 Jan;7(1):93–96. [PubMed]
8. Williams LS, Bruno A, Rouch D, Marriott DJ. Stroke patients’ knowledge of stroke. Influence on time to presentation. Stroke. 1997 May;28(5):912–915. [PubMed]
9. Kothari R, Sauerbeck L, Jauch E, Broderick J, Brott T, Khoury J, Liu T. Patients’ awareness of stroke signs, symptoms, and risk factors. Stroke. 1997 Oct;28(10):1871–1875. [PubMed]
10. Awareness of stroke warning signs--17 states and the U.S. Virgin Islands, 2001. MMWR Morb Mortal Wkly Rep. 2004 May 7;53(17):359–362. [PubMed]
11. Schneider AT, Pancioli AM, Khoury JC, Rademacher E, Tuchfarber A, Miller R, Woo D, Kissela B, Broderick JP. Trends in community knowledge of the warning signs and risk factors for stroke. JAMA. 2003 Jan 15;289(3):343–346. [PubMed]
12. McSweeney JC, Cody M, O’Sullivan P, Elberson K, Moser DK, Garvin BJ. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003 Nov 25;108(21):2619–2623. [PubMed]
13. National Stroke Association. Women and Stroke; Unique Symptoms in Women. http://www.stroke.org/site/PageServer?pagename=WOMSYMP.
14. Adams HP, Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE., 3rd Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 Jan;24(1):35–41. [PubMed]
15. Rathore SS, Hinn AR, Cooper LS, Tyroler HA, Rosamond WD. Characterization of incident stroke signs and symptoms: findings from the atherosclerosis risk in communities study. Stroke. 2002 Nov;33(11):2718–2721. [PubMed]
16. Zerwic J, Hwang SY, Tucco L. Interpretation of symptoms and delay in seeking treatment by patients who have had a stroke: exploratory study. Heart and Lung. 2007 Jan–Feb;36(1):25–34. [PubMed]
17. Glader EL, Stegmayr B, Norrving B, Terent A, Hulter-Asberg K, Wester PO, Asplund K. Sex differences in management and outcome after stroke: a Swedish national perspective. Stroke. 2003 Aug;34(8):1970–1975. [PubMed]
18. Simpson CR, Wilson C, Hannaford PC, Williams D. Evidence for age and sex differences in the secondary prevention of stroke in Scottish primary care. Stroke. 2005 Aug;36(8):1771–1775. [PubMed]
19. McInnes C, McAlpine C, Walters M. Effect of gender on stroke management in Glasgow. Age Ageing. 2008 Mar;37(2):220–222. [PubMed]
20. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005 Mar 31;352(13):1293–1304. [PubMed]
21. Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA. 2006 Jan 18;295(3):306–313. [PubMed]
22. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115–126. [PubMed]
23. Rost NS, Wolf PA, Kase CS, Kelly-Hayes M, Silbershatz H, Massaro JM, D’Agostino RB, Franzblau C, Wilson PW. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke. 2001 Nov;32(11):2575–2579. [PubMed]
24. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557–1565. [PubMed]
25. Gargano JW, Wehner S, Reeves M. Sex differences in acute stroke care in a statewide stroke registry. Stroke. 2008 Jan;39(1):24–29. [PubMed]
26. Holroyd-Leduc JM, Kapral MK, Austin PC, Tu JV. Sex differences and similarities in the management and outcome of stroke patients. Stroke. 2000 Aug;31(8):1833–1837. [PubMed]
27. Roquer J, Campello AR, Gomis M. Sex differences in first-ever acute stroke. Stroke. 2003 Jul;34(7):1581–1585. [PubMed]
28. Kapral MK, Fang J, Hill MD, Silver F, Richards J, Jaigobin C, Cheung AM. Sex differences in stroke care and outcomes: results from the Registry of the Canadian Stroke Network. Stroke. 2005 Apr;36(4):809–814. [PubMed]
29. Di Carlo A, Lamassa M, Baldereschi M, Pracucci G, Basile AM, Wolfe CD, Giroud M, Rudd A, Ghetti A, Inzitari D. Sex differences in the clinical presentation, resource use, and 3-month outcome of acute stroke in Europe: data from a multicenter multinational hospital-based registry. Stroke. 2003 May;34(5):1114–1119. [PubMed]
30. Niewada M, Kobayashi A, Sandercock PA, Kaminski B, Czlonkowska A. Influence of gender on baseline features and clinical outcomes among 17,370 patients with confirmed ischaemic stroke in the international stroke trial. Neuroepidemiology. 2005;24(3):123–128. [PubMed]
31. Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke. 2001 Dec 1;32(12):2735–2740. [PubMed]
32. Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, Ganiats TG, Gomes AS, Gornik HL, Gracia C, Gulati M, Haan CK, Judelson DR, Keenan N, Kelepouris E, Michos ED, Newby LK, Oparil S, Ouyang P, Oz MC, Petitti D, Pinn VW, Redberg RF, Scott R, Sherif K, Smith SC, Jr, Sopko G, Steinhorn RH, Stone NJ, Taubert KA, Todd BA, Urbina E, Wenger NK. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481–1501. [PubMed]