O r i g i n a l P a p e r

Sex Differences in the HypertensivePopulation With Chronic IschemicHeart Disease

Vivencio Barrios, MD;1 Carlos Escobar, MD;2 Vicente Bertomeu, MD;3

Nekane Murga, MD;4 Carmen de Pablo, MD;1 Alberto Calderon, MD5

Cardiopatıa Isquemica Cronica e HipertensionArterial en la Practica Clınica en Espana(CINHTIA) was a survey designed to assess theclinical management of hypertensive outpatientswith chronic ischemic heart disease. Sex differ-ences were examined. Blood pressures (BP) wasconsidered controlled at levels of <140 ⁄ 90 or<130 ⁄ 80 mm Hg in diabetics (European Societyof Hypertension ⁄ European Society of Cardiology2003); low-density lipoprotein cholesterol(LDL-C) was considered controlled at levels<100 mg ⁄ dL (National Cholesterol EducationProgram Adult Treatment Panel III). In total,2024 patients were included in the study. Womenwere older, with a higher body mass index andan increased prevalence of atrial fibrillation.Dyslipidemia, smoking, sedentary lifestyle, andperipheral arterial disease were more frequent inmen. In contrast, diabetes, left ventricular

hypertrophy, and heart failure were more com-mon in women. BP and LDL-C control rates,although poor in both groups, were better inmen (44.9% vs 30.5%, P<.001 and 33.0% vs25.0%, P<.001, respectively). Stress testing andcoronary angiography were more frequentlyperformed in men. J Clin Hypertens (Greenwich).2008;10:779–786. ª2008 Le Jacq

Cardiovascular disease is the most importantcause of death among women.1 Moreover,

the progressive aging of the population, a seden-tary lifestyle, and the increased prevalence of dia-betes and obesity may worsen this situation inthe future.2,3 Despite that, it seems that manyphysicians and patients do not actually perceivethe coronary risk in women.4 This could beat least partially due to confidence in thewell-known cardioprotective effect of femalehormones but also to the fact that, in the pastdecades, most clinical trials included primarilymale patients. As a result, many physicians havenot realized the frequency of heart disease inwomen.2 Fortunately, in the last few years theinformation provided from different studies hasincreased the sensitivity of this issue.2,5 Moreinformation is necessary for better clinical man-agement in this population.

Treatment of hypertension markedly reduces therisk of ischemic disease.6 Current recommendationsestablish that patients with hypertension and coro-nary heart disease should be treated aggressively toattain blood pressure (BP) targets lower than those

From the Department of Cardiology, Hospital Ramon yCajal, Madrid;1 the Department of Cardiology,Hospital Infanta Sofıa, Madrid;2 the Department ofCardiology, Hospital Universitario San Juan, Alicante;3

the Department of Cardiology, Hospital de Basurto,Bilbao;4 and the Primary Care Center RosaLuxemburgo, Madrid, Spain5

Address for correspondence: Vivencio Barrios, MD,Department of Cardiology, Hospital Ramon y Cajal,Carretera De Colmenar km 9,100, 28034 Madrid,SpainE-mail: vbarriosa@meditex.esManuscript received April 23, 2008; revised July 13, 2008;accepted July 24, 2008

doi: 10.1111/j.1751-7176.2008.00020.x

VOL. 10 NO. 10 OCTOBER 2008 THE JOURNAL OF CLINICAL HYPERTENSION 779

in the general population.2,7,8 A growing interest inthe association of hypertension and ischemic heartdisease led to the recent publication of a statementfrom the American Heart Association on thistopic.8

Although some surveys devoted to patients withischemic heart disease have been developed andhave assessed the clinical profile of this popula-tion,9–12 there is only limited information specifi-cally focused on hypertensive patients withcoronary heart disease. Cardiopatıa IsquemicaCronica e Hipertension Arterial en la PracticaClınica en Espana (CINHTIA) is a cross-sectionalmulticenter survey to determine the clinical profileand management of hypertensive outpatients withchronic ischemic heart disease attended by cardiolo-gists in clinical practice in Spain. In this manuscript,the influence of sex on these issues is examined.

PATIENTS AND METHODSA total of 112 investigators, all cardiologists, par-ticipated in this study performed during the secondquarter of 2006. Each investigator was asked toinclude consecutive patients aged 18 years or older,male or female, with an established diagnosis ofhypertension and chronic ischemic heart disease.Patients with an acute coronary syndrome withinthe previous 3 months before inclusion wereexcluded. Biodemographic data, risk factors, historyof cardiovascular disease, and the different treat-ments patients were receiving were recorded. Allpatients underwent a complete physical examina-tion and had a complete blood test (hematologyand biochemistry with a lipid profile) performedwithin the previous 6 months.

BP readings were taken following the 2003European guidelines.13 The visit BP was the averageof 2 separate measurements taken by the examiningphysician; a third measure was obtained when therewas a difference of �5 mm Hg between the 2 read-ings. Hypertension was diagnosed when patientshad a systolic BP level �140 mm Hg or a diastolicBP level �90 mm Hg (130 ⁄80 mm Hg, respec-tively, for diabetics) or a history of hypertensionand taking antihypertensive medication. AdequateBP control was defined as a systolic BP level<140 mm Hg and a diastolic BP level <90 mm Hg(<130 and <80 mm Hg for diabetics).13 Low-den-sity lipoprotein cholesterol (LDL-C) <100 mg ⁄dLwas considered under good control.14 Sedentarylifestyle was defined as physical activity less than a30-minute daily walk.

Chronic ischemic heart disease was defined byany of the following: stable angina, clinically

defined as typical chest pain with the demonstra-tion of myocardial ischemia that occurs on exertionand is relieved by rest; evidence of myocardialischemia assessed by any stress test performed>3 months before inclusion in the study; a historyof myocardial infarction; or previous revasculariza-tion more than 3 months before the trial. The pres-ence of organ damage or associated clinicalconditions was recorded from the patients’ clinicalhistory. Renal insufficiency was considered to be aserum creatinine level >1.5 mg ⁄dL in men and>1.4 mg ⁄dL in women.13 The diagnosis of left ven-tricular hypertrophy was established by electro-cardiography (Sokolow–Lyon voltage >38 mm;Cornell voltage duration product >2440 mm·ms)and ⁄or echocardiography (left ventricular massindex �125 g ⁄m2 in men and �110 g ⁄m2 inwomen).13

Statistical AnalysisChi-square testing was used to analyze the relation-ship between categorical variables. Comparison ofcontinuous variables between groups was performedusing the Student’s t-test. A logistic regression analy-sis was performed to determine which factors couldbe associated with BP control. Clinical characteristicsof study population, cardiovascular risk factors,organ damage, antihypertensive treatments, concom-itant treatments, and biochemical parameters wereincluded as independent variables in the logisticregression analysis. A P value <.05 was used as thelevel of statistical significance. Database recordingwas subjected to internal consistency rules andranges to control inconsistencies ⁄ inaccuracies in thecollection and tabulation of data (SPSS version 12.0,Data Entry, SPSS, Inc., Chicago, IL).

RESULTSIn the CINHTIA study, a total of 2024 hypertensivepatients with chronic ischemic heart disease wereincluded (31.7% female). Table I summarizes thebiodemographic data, cardiovascular risk factors,organ damage, physical examination results, andlaboratory parameters. Women were older and hada higher body mass index and an increased preva-lence of atrial fibrillation. Although angina was themost frequent clinical presentation in both sexes, itwas more common in women. By contrast, the his-tory of myocardial infarction and revascularizationwas significantly more common in men. The pres-ence of concomitant cardiovascular risk factors andorgan damage was common in both sexes. Dyslipi-demia, smoking, sedentary lifestyle, and peripheralarterial disease were more frequent in men and

THE JOURNAL OF CLINICAL HYPERTENSION VOL. 10 NO. 10 OCTOBER 2008780

diabetics; left ventricular hypertrophy and heart fail-ure were more common in women. Systolic anddiastolic BP, heart rate, total cholesterol, LDL-C,high-density lipoprotein cholesterol and serum fast-ing glucose values were higher in women, whileserum uric acid levels were higher in men.

Almost all patients were taking at least 4 drugs,without significant differences between sexes. How-ever, men were taking more antiplatelet agents andshowed a trend toward using more lipid-loweringdrugs. Antidiabetic medication and anticoagulantswere used more frequent in women (Figure 1). InFigure 2, the prescribed antihypertensive drugs arelisted. b-Blockers were the agents most commonlyused in both groups. Though the total number of

drugs was similar in both sexes, distribution dif-fered. Thus, the prescription of b- and a-blockerswere more common in men, and calcium channelblockers, diuretics, and angiotensin receptorblockers were more common in women.

Overall BP and LDL-C control rates (Figure 3)were better in men than in women (44.9% vs30.5%, P<.001 and 33.0% vs 25.0%, P<.001,respectively). With a BP goal <130 ⁄80 mm Hg(current guidelines recommended for hypertensivepatients with concomitant coronary heart diseaseor diabetes), BP control was also worse in women(27.2% vs 17.7%, P=.001). In a multivariate analy-sis, female sex was a predictor of poor BP control(odds ratio, 1.43; 95% confidence interval,

Table I. Clinical Characteristics of the Study Population (N=2024)

Male (n=1382; 68.3%) Female (n=642; 31.7%) P Value

Age, y 65.7±10.3 68.2±9.1 <.0001

BMI, kg ⁄ m2 28.0±3.5 28.8±4.6 .001Atrial fibrillation, % 13.3 23.8 <.0001LVEF, % 57.4±11.4 58.6±11.6 .25

Clinical manifestation of chronic ischemic heart diseasea

Angina, % 67.0 73.3 .003Myocardial infarction, % 48.7 34.3 <.0001Revascularization, % 48.5 33.8 <.0001

Evidence of ischemia, % 39.4 43.7 .042Cardiovascular risk factors

Dyslipidemia, % 80.0 75.2 .009

Current smoker, % 15.5 5.2 <.0001Ex-smoker (>1 year quit smoking), % 41.4 10.2 <.0001Diabetes, % 27.3 43.2 <.0001

Sedentary lifestyle, % 75.4 60.9 <.0001Metabolic syndrome, % 53.9 66.1 <.0001

Organ damageLeft ventricular hypertrophy, % 46.6 54.9 .001

Heart failure, % 14.5 26.8 <.0001Peripheral artery disease, % 18.5 10.3 <.0001Renal function insufficiency, % 12.4 12.7 .88

Stroke, % 7.9 9.6 .24Physical examination

SBP, mm Hg 141.1±17.8 146.3±17.5 <.0001

DBP, mm Hg 81.2±11.2 83.2±11.3 <.0001HR, beats ⁄ min 68.5±11.0 71.5±10.6 <.0001

Biochemical parametersTotal cholesterol, mg ⁄ dL 195.4±44.3 207.8±42.4 <.0001

Triglycerides, mg ⁄ dL 142.8±78.9 147.4±73.4 .24LDL-C, mg ⁄ dL 114.4±36.4 119.6±34.4 .004HDL-C, mg ⁄ dL 49.3±18.7 51.2±16.5 .04

Serum fasting glucose, mg ⁄ dL 114.6±35.7 125.8±43.5 <.0001Creatinine, mg ⁄ dL 1.24±1.3 1.18±1.2 .33Uric acid, mg ⁄ dL 7.1±6.9 6.5±5.6 .09

Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol;HR, heart rate; LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; SBP, systolic blood pressure.aA patient may have more than one diagnosis.

VOL. 10 NO. 10 OCTOBER 2008 THE JOURNAL OF CLINICAL HYPERTENSION 781

1.08–1.90). BP control rates were also analyzedaccording to the clinical manifestations of chronicischemic heart disease (Table II). In all cases

(angina, evidence of ischemia, myocardial infarc-tion, or previous revascularization), BP control rateswere higher in men. In both sexes, the history of

0

10

20

30

40

50

60

70

80

90

100

≥4 Drugs AntihypertensiveDrugs

Antiplatelets Lipid-LoweringDrugs

Antidiabetic Drugs

Anticoagulants

88.9% 89.4%

99.7% 99.5%

91.8%

80.6%76.0%

72.5%

23.0%

38.6%

10.7%

21.1%

P=NS

P=.055

P<.001

P<.001

P<.001

P=NS

MaleFemale

Figure 1. Treatment of the study population.

0

10

20

30

40

50

60

70

80

90

100

β-Blockers CalciumChannelBlockers

ACEi Diuretics ARB α-Blockers

70.1%

60.8%

41.6%

50.2%

43.1% 44.0%

29.8%

47.0%

30.6%

38.1%

4.9% 2.9%

P<.001

P<.001P=NS

P=.001

P=.03

P<.001

Others

1.6% 1.7%

P=NS

MaleFemale

Figure 2. Antihypertensive medication in the study. ACEi indicates angiotensin-converting enzyme inhibitors; ARB,angiotensin receptor blockers.

THE JOURNAL OF CLINICAL HYPERTENSION VOL. 10 NO. 10 OCTOBER 2008782

revascularization was associated with better BPcontrol rates.

Finally, the diagnostic methods used in this pop-ulation according to sex were examined. Exercisetests and cardiac catheterization tests were morecommonly performed in men, and radioisotopicexaminations were performed more in women,without differences in the frequency of electrocardi-ography, echocardiography, or stress echocardio-graphy (Figure 4).

DISCUSSIONEpidemiologic studies have established a strongassociation between hypertension and coronaryheart disease. Indeed, about 10% of hypertensivepatients who are seen in primary care settings and>20% seen in cardiologist clinics have ischemicheart disease.15 On the other hand, more thanthree-quarters of patients with coronary arterydisease have a clinical history of hypertension.16

Despite that coronary heart disease has been tradi-tionally considered a male illness, data show thatthis is one of the most important causes of mortal-ity in women.1 Moreover, recent studies havereported that women with acute coronary syn-dromes have a similar number of17,18 or even moremorbid events than do men.19

Several studies in the past few years haveassessed the differences between sexes in clinicalfindings and management of coronary heart disease.There is little information about these differen-ces in the hypertensive population.9–12,17,18 TheCINHTIA survey may provide relevant informationabout sex differences.

Because patients included in randomized clinicaltrials are selected and may not always represent the‘‘real world’’ of daily practice, the development ofthis type of survey may be of clinical interest.20

The results clearly show that there are significantdifferences between sexes in the clinical profile;women are older and more obese. The presence ofconcomitant cardiovascular risk factors and organdamage was common in both sexes. But while dysl-ipidemia, smoking, sedentary lifestyle, and peri-pheral arterial disease were more frequent in men,diabetes, left ventricular hypertrophy, and heartfailure were more common in women. These differ-ences observed between sexes are similar to thoserecently published from research in patients withacute coronary syndromes.18 The presence of morecases of left ventricular hypertrophy and heart fail-ure in women is consistent with the well-knownimpact of diabetes on the development of cardiachypertensive complications.21,22 It is likely that

sex differences in chemokine ⁄cytokine markers ofatherosclerosis may explain these differences.23

Although previous studies have shown similar clini-cal profile differences between sexes, the slower rateof decline in smoking over the past decade inwomen may modify the risk profile of femalepatients in the future.2,7–9,12,24

BP control is crucial to improve prognosis inpatients with coronary heart disease. Although BPcontrol is still far from optimal in Spain, in recentyears it has markedly improved, from <20% toabout 40%, not only in the primary care settingbut in secondary care centers as well.24 Notably,BP control has improved not only in the hyper-tensive general population but also in patients withcoronary heart disease.10,25,26 This improvement isdue to many factors, the most important of whichmay be an increasing concern about the need foradequate BP control. In this survey, almost allpatients were taking several antihypertensive drugs;b-blockers were the most commonly prescribeddrugs. However, as in the general hypertensive pop-ulation, BP in men with hypertension and coronaryheart disease was better controlled than inwomen.27 The classes of antihypertensive agentssignificantly differed between sexes. It is likely thatthis dissimilar distribution in the antihypertensive

0

20

40

60

80

100

Blood Pressure LDL-C

44.9%

30.5% 33.0%25.0%

P<.001

P=.001

MaleFemale

Figure 3. Blood pressure and low-density lipoproteincholesterol (LDL-C) control rates.

Table II. Blood Pressure (BP) Control Rates According

to the Different Clinical Manifestations of ChronicIschemic Heart Disease

Clinical Manifestation

of Chronic Ischemic

Heart Disease

BP Control

Rates (%)

P ValueMale Female

Angina 42.4 28.6 <.001Evidence of ischemia 43.8 33.2 <.001Myocardial infarction 48.3 31.2 <.001Revascularization 47.7 37.0 <.001

VOL. 10 NO. 10 OCTOBER 2008 THE JOURNAL OF CLINICAL HYPERTENSION 783

drugs may, at least in part, play a role in degree ofBP control.7,28

Recent guidelines have also established a BPobjective <130 ⁄80 mm Hg in hypertensive patientswith diabetes and coronary heart disease. Thus, weanalyzed the sample with this lower BP target. Ourdata again showed worse BP control in womendespite that diabetes is more common in this popu-lation. In the multivariate analysis, sex was a pre-dictor of poor BP control independently of thepresence of diabetes.

Several studies have analyzed the lipid (LDL-C)control rate in patients with coronary heart disease.These surveys have shown that not only in primarycare but also in cardiology practices control is stillfar from optimal.9,10,29,30 Our data show thatalthough the majority of patients are taking lipid-lowering drugs, fewer than a third of dyslipidemicpatients have their LDL-C controlled to goal levels.This situation is even worse in women and seemsto be clearly related to less use of lipid-loweringdrugs in women.12

Of interest, the prevalence of atrial fibrillationwas more frequent in women; this may explain thehigher use of anticoagulants in this population.However, since some patients with coronary heartdisease and atrial fibrillation may benefit from dual

treatment with antiplatelet agents and anticoagu-lants, the observed underuse of antiplatelets inwomen could be clinically relevant for cardiovascu-lar outcomes.2

To treat patients with ischemic heart diseaseadequately, it is necessary to use a correct diagnos-tic approach. Although the sensitivity and specific-ity of the different cardiac diagnostic methods arewell defined in men, they are less well establishedin women.8,31 In fact, women may have false-posi-tive results on exercise tests more frequently thanmen, and by contrast, negative electrocardiographyresults in women do not exclude ischemic heart dis-ease.8 Despite that women have a similar or slightlyhigher prevalence of angina,32 this survey indicatedthat men were more likely to undergo stress testsand coronary angiography. As a result, coronaryheart disease in hypertensive women may be under-diagnosed.17,18 This might have relevant prognosisimplications.

LimitationsThe cross-sectional design of the study was chosento best represent the ‘‘real world’’ of clinical prac-tice. Consequently, a large population of hyperten-sive patients recruited by consecutive sampling wasincluded in the trial. This methodology has its

0

10

20

30

40

50

60

70

80

90

100

RadioisotopicExamination

Exercise TestEchocardiographyElectrocardiography StressEchocardiography

CardiacCatheterization

100% 99.7%

81.7% 79.7%

62.9%

45.6%

22.0%

27.1%

5.3% 4.5%

63.4%

49.8%

P=NS

P=.019

P<.001

P=NS

P<.001

P=NS

MaleFemale

Figure 4. Diagnostic procedures according to sex.

THE JOURNAL OF CLINICAL HYPERTENSION VOL. 10 NO. 10 OCTOBER 2008784

limitations, since it reduces the level of control thatcan be exercised to reduce variation and bias.However, the large number of patients includedand the nature of the end points measured, with nocomparators under review, minimizes this theoreti-cal limitation. Because our study was carried out ina population attended by cardiologists in Spain, thedata could probably only be generalized to thosecountries with the same health care delivery andcardiovascular risk profile. Finally, menopause isone of the main conditions that raise the risk ofdeveloping ischemic heart disease in womenthrough different mechanisms, such as an increasein systolic BP. The use of hormone replacementtherapy in postmenopausal women could also havean influence on the results of the study; the preva-lence of premenopausal women was only 6.5%.

CONCLUSIONSThe clinical profile of a hypertensive populationwith coronary heart disease treated by cardio-logists differed between sexes. Coronary heart dis-ease in women appeared to be undertreated andunderdiagnosed, which may in part explain thepoorer BP and LDL-C control rates observed inthis population. These results highlight the needfor ongoing medical education to improve the rec-ognition and management of coronary heart dis-ease in women, with the goal of reducingcardiovascular risk.

Acknowledgments: The authors wish to express their gratitudeto all investigators who actively participated in this study. Thepresent study was supported by an unrestricted grant providedby Recordati Espana S.L. All data have been recorded andanalyzed independently to prevent bias.

REFERENCES

1 Fox CS, Evans JC, Larson MG, et al. Temporal trends incoronary heart disease mortality and sudden cardiac deathfrom 1950 to 1999. The Framingham Heart Study. Circu-lation. 2004;110:522–527.

2 Mosca L, Banka CL, Benjamin EJ, et al. Evidence-basedguidelines for cardiovascular disease prevention inwomen: 2007 update. Circulation. 2007;115:1481–1501.

3 Li TY, Rana JS, Manson JE, et al. Obesity as comparedwith physical activity in predicting risk of coronary heartdisease in women. Circulation. 2006;113:499–506.

4 Mosca L, Linfante AH, Benjamin EJ, et al. National studyof physician awareness and adherence to cardiovasculardisease prevention guidelines in the United States. Circula-tion. 2005;111:499–510.

5 Mosca L, Appel LJ, Benjamin EJ, et al. Evidence-basedguidelines for cardiovascular disease prevention inwomen. J Am Coll Cardiol. 2004;43:900–921.

6 Anguita M, Rodriguez M, Ojeda S, et al. Clinical out-come and reversibility of systolic dysfunction in patientswith dilated cardiomyopathy due to hypertension andchronic heart failure. Rev Esp Cardiol. 2004;57:834–841.

7 Mancia G, De Backer G, Dominiczak A, et al. 2007Guidelines for the Management of Arterial Hypertension:The Task Force for the Management of Arterial Hyper-tension of the European Society of Hypertension (ESH)and of the European Society of Cardiology (ESC).J Hypertens. 2007;25:1105–1187.

8 Rosendorff C, Black HR, Cannon CP, et al. Treatment ofhypertension in the prevention and management of ische-mic heart disease: a scientific statement from the Ameri-can Heart Association Council for High Blood PressureResearch and the Councils on Clinical Cardiology andEpidemiology and Prevention. Circulation. 2007;115:2761–2788.

9 EUROASPIRE Study Group. EUROASPIRE. A EuropeanSociety of Cardiology survey of secondary prevention ofcoronary heart disease: principal results. Eur Heart J.1997;18:1569–1582.

10 EUROASPIRE II Study Group. Lifestyle and risk factormanagement and use of drug therapies in coronarypatients from 15 countries. Principle results fromEUROASPIRE II Euro Heart Survey Programme. EurHeart J. 2001;22:554–572.

11 Boersma E, Keil U, De Bacquer D, et al. Blood pressure isinsufficiently controlled in European patients with estab-lished coronary heart disease. J Hypertens. 2003;21:1831–1840.

12 Hippisley-Cox J, Pringle M, Crown N, et al. Sex inequali-ties in ischaemic heart disease in general practice: crosssectional survey. BMJ. 2001;322:832–836.

13 European Society of Hypertension-European Society ofCardiology Guidelines Committee. 2003 European Societyof Hypertension – European Society of Cardiology guide-lines for the management of arterial hypertension. JHypertens. 2003;21:1011–1053.

14 National Cholesterol Education Program (NCEP) ExpertPanel on Detection, Evaluation, and Treatment of HighBlood Cholesterol in Adults (Adult Treatment Panel III).Third Report of the National Cholesterol Education Pro-gram (NCEP) Expert Panel on Detection, Evaluation, andTreatment of High Blood Cholesterol in Adults (AdultTreatment Panel III) final report. Circulation. 2002;106:3143–21.

15 Barrios V, Escobar C, Calderon A, et al. Cardiovascularrisk profile and risk stratification of the hypertensive pop-ulation attended by general practitioners and specialists inSpain. The CONTROLRISK study. J Hum Hypertens.2007;21:479–485.

16 Bhatt DL, Steg PG, Ohman EM, et al. International prev-alence, recognition, and treatment of cardiovascular riskfactors in outpatients with atherothrombosis. JAMA.2006;295:180–189.

17 19Radovanovic D, Erne P, Urban P, et al. Gender dif-ferences in management and outcomes in patients withacute coronary syndromes: results on 20,290 patientsfrom the AMIS Plus Registry. Heart. 2007;93:1369–1375.

18 Alfredsson J, Stenestrand U, Wallentin L, et al. Genderdifferences in management and outcome in non-ST-eleva-tion acute coronary syndrome. Heart. 2007;93:1357–1362.

19 Ferrer-Hita JJ, Domınguez-Rodrıguez A, Garcıa-GonzalezMJ, et al. Female gender is an independent predictor ofin-hospital mortality in patients with ST segment eleva-tion acute myocardial infarction treated with primaryangioplasty. Med Intensiva. 2008;32:110–114.

20 Steg PG, Lopez-Sendon J, Lopez de Sa E, et al. Externalvalidity of clinical trials in acute myocardial infarction.Arch Intern Med. 2007;167:68–73.

21 Conen D, Ridker PM, Mora S, et al. Blood pressure andrisk of developing type 2 diabetes mellitus: the Women’sHealth Study. Eur Heart J. 2007;28:2937–2943.

VOL. 10 NO. 10 OCTOBER 2008 THE JOURNAL OF CLINICAL HYPERTENSION 785

22 Schillaci G, Pirro M, Pucci G, et al. Different impact ofthe metabolic syndrome on left ventricular structure andfunction in hypertensive men and women. Hypertension.2006;47:881–886.

23 Leung J, Jayachandran M, Kendall-Thomas J, et al. Pilotstudy of sex differences in chemokine ⁄ cytokine markersof atherosclerosis in humans. Gend Med. 2008;5:44–52.

24 Schnoll RA, Patterson F, Lerman C. Treating tobaccodependence in women. J Womens Health (Larchmt).2007;16:1211–1218.

25 Barrios V, Banegas JR, Ruilope LM, et al. Evolution ofblood pressure control in Spain. J Hypertens. 2007;25:1975–1977.

26 Tranche S, Lopez I, Mostaza JM, et al. Control of coro-nary risk factors in secondary prevention: PRESENAPstudy. Med Clin. 2006;127:765–769.

27 Keyhani S, Scobie JV, Hebert PL, et al. Gender disparitiesin blood pressure control and cardiovascular care in anational sample of ambulatory care visits. Hypertension.2008;51:1149–1155.

28 Ho PM, Magid DJ, Shetterly SM, et al. Medication non-adherence is associated with a broad range of adverseoutcomes in patients with coronary artery disease. AmHeart J. 2008;155:772–779.

29 De Velasco JA, Cosin J, Lopez-Sendon JL, et al. New dataon secondary prevention of myocardial infarction inSpain. Results of the PREVESE II study. Rev Esp Cardiol.2002;55:601–609.

30 Qureshi AI, Suri MF, Guterman LR, et al. Ineffective sec-ondary prevention in survivors of cardiovascular events inthe US population. Arch Intern Med. 2001;161:1621–1628.

31 Metz LD, Beattie M, Hom R, et al. The prognostic valueof normal exercise myocardial perfusion imaging andexercise echocardiography: a meta-analysis. J Am CollCardiol. 2007;49:227–237.

32 Hemingway H, Langenberg C, Damant J, et al. Prevalenceof angina in women versus men: a systematic review andmeta-analysis of international variations across 31 coun-tries. Circulation. 2008;117:1526–1536.

THE JOURNAL OF CLINICAL HYPERTENSION VOL. 10 NO. 10 OCTOBER 2008786