Abstract
Hypertension is a major risk factor for cardiovascular disease, which is the leading cause of death in women. Aim. To evaluate blood pressure control, prevalence of concomitant cardiovascular risk factors, subclinical and clinical organ damage, and treatment according to gender. Methods. 11,562 patients (49% women) from the cross-sectional I-inSyst survey in primary care were included. Results. Blood pressure control in women (21.8%) and men (21.2%) was similar, despite a slightly older age (64.9 vs 63 years, p<0.0001). Women had less concomitant cardiovascular risk factors and organ damage, with the exception of diabetes, cerebrovascular and renal disease, than men. They received more antihypertensive drugs than men (1.7 ± 0.9 vs 1.5 ± 0.9, p<0.0001). Diuretics were more (45% vs 36.5%, p<0.0001), calcium-channel blockers (26% vs 29%, p<0.003) and angiotensin-converting enzyme inhibitors (20% vs 22%, p<0.02) were less commonly prescribed in women than in men. Different clinical factors (i.e. age, duration of hypertension, smoking) in women and men were associated with blood pressure control, but gender itself was not. Conclusions. In this group of treated hypertensive patients, blood pressure control in women and men was not different. Women had a lower prevalence of most cardiovascular risk factors, subclinical and clinical organ damage. Antihypertensive drug treatment varied according to gender.
Introduction
Hypertension is a major, but potentially modifiable risk factor for cardiovascular (CV) disease morbidity and mortality, both in women and in men (Citation1,Citation2). CV disease (CVD) is the leading cause of death in women worldwide (Citation3–5). Yet several studies have shown that women are less treated than men and that physicians do not actually perceive CV risk in women (Citation2,Citation6). This gender disparity is stated to contribute to the difference in CVD mortality (Citation7).
Guidelines on the management of hypertension recommend targeting at least a systolic blood pressure (SBP) <140 mmHg and a diastolic blood pressure (DBP) <90 mmHg, which will generally be attained using two or more antihypertensive agents (Citation8). Individuals with hypertension frequently cluster other CV risk factors, which not only adds to their overall CV risk (Citation9) but also influences blood pressure (BP) control rate (Citation10). Target BP and choice of the first-line antihypertensive class therefore depend on the presence of concomitant CV risk factors and comorbidity conditions present in the patient (Citation11).
In spite of the strong beneficial data of both epidemiological and intervention studies, less than 50% of hypertensive individuals are being treated to goal (Citation12,Citation13). Significant gender differences in levels of BP control have been reported, but the data on the association of gender with BP control are conflicting (Citation14).
In this study, we analysed the data from the I-inSYST survey (Citation15), a large cross-sectional survey on the management of hypertension in Belgium, to determine, among patients with treated hypertension, the gender difference in BP control, prevalence of other CV risk factors, subclinical organ damage, established CV and renal disease, treatment and factors associated with BP control.
Methods
We performed a sub-analysis of women and men who participated in the I-inSYST survey. The methodology of the I-inSyst study was described in detail in the referent manuscript (Citation15).
Study sample
From December 2003 to June 2004, 994 primary care physicians throughout Belgium enrolled 13,774 consecutive treated hypertensive patients (≥18 years old).
The following data were collected using a structured questionnaire on demographic and anthropometric data (age, sex, height, weight, duration of hypertension, BP and heart rate), CV risk factors [e.g. body mass index (BMI), waist circumference, smoking status, hypercholesterolemia, diabetes mellitus (DM), and familial history of premature CVD], subclinical organ damage [e.g. left ventricle hypertrophy (LVH), increased carotid wall thickening or plaque, further in the text referred to as IMT: intima media thickness], microalbuminuria (MAU) and slight increase in serum creatinine (115–133 µmol/l for men and 107–124 µmol/l for women), present and past CVD (e.g. cerebrovascular, coronary artery, peripheral artery and renal disease), antihypertensive drug treatment and lifestyle modifications. Whether the treatment was adjusted and the reason were also recorded. Except for the anthropometric and BP measurements, the available information of the files was used (data not older than 6 months), as I-inSYST was a non-interventional study in primary care. Patients were questioned about changes in their lifestyles on earlier recommendations from their physician. The accuracy of the information was verified in a random sample (5%).
BP was measured, as recommended by the guidelines, in the sitting position after 5 min of rest, using a calibrated device with an appropriate cuff. BP was measured at least twice with 1–2-min interval (Citation16). Different age groups were predefined: <50, 50–79 and ≥80 years. Overweight and obesity were defined respectively as a BMI between 25–29.9 and ≥30 kg/m². Abdominal obesity was defined as an abdominal circumference ≥102 cm for men and ≥88 cm for women. The presence of hypercholesterolemia was defined as a total cholesterol >6.5 mmol/l or LDL-C >4.0 mmol/l or HDL-C<1.0 mmol/l for men and <1.2 mmol/l for women. The definitions of the risk stratification of the 2003 European Society of Hypertension–European Society of Cardiology (ESH/ESC) guidelines were used (Citation16).
The study was approved by a central independent Ethics Committee. A signed informed consent was obtained from all patients.
Hypertension control
Hypertension was defined as a mean SBP≥140 mmHg and/or mean DBP≥90 mmHg, or current treatment for hypertension. Overall BP control was defined as a SBP<140 mmHg and a DBP<90 mmHg. A SBP≥140 mmHg and a DBP<90 mmHg was considered on-treatment isolated systolic hypertension (ISH). An SBP<140 mmHg and a DBP ≥90 mmHg were considered on-treatment isolated diastolic hypertension (IDH).
Statistical analysis
The statistical analysis was performed with SAS statistical software version 8.2 (SAS Institute Inc., Cary, NC, USA). All tests were two-sided using a significance level of 0.05. Continuous variables are described as mean values with their corresponding standard deviation (SD), and dichotomous variables are described as counts and percentages. To evaluate the differences in clinical characteristics between men and women, chi-square tests and Student's t-tests were applied as appropriate. Stepwise multiple logistic regression models were used to assess the relationship between the prevalence of controlled hypertension and clinical variables according to gender. Adjustment for age, SBP and DBP, BMI, abdominal obesity, presence of diabetes mellitus, smoking, number of antihypertensive drugs and duration of hypertension (continuous variable) was performed. Odds ratios (OR) and corresponding 95% confidence intervals (CI) are reported.
Results
Study sample
shows the gender-specific demographic characteristics of the 11,562 evaluable (patients with missing data were excluded for analysis) patients (ratio men/women: 1.03). Mean age of the 5691 women was significantly higher, because of a higher proportion of >80-year-old patients and a lower proportion of <50-year-old patients than in the male subgroup (p<0.0001). Mean BMI did not differ, but significantly less women than men presented with weight excess, defined as BMI≥25 kg/m2 (respectively 67% compared with 74%, p<0.0001).
Table I. Demographic characteristics, cardiovascular risk factors, subclinical organ damage and established cardiovascular and renal disease by gender.
Concomitant CV risk factors and disease
The prevalence of concomitant CV risk factors, subclinical organ damage and established CV and renal disease is shown in . The distribution of the number of the different CV risk factors (), subclinical organ damage and established CV and renal disease, was similar in women and men, irrespective the type of uncontrolled (ISH, IDH or combined) hypertension (data not shown), while the mean number of CV risk factors, subclinical and clinical organ damage was significantly lower in women than in men (1.4±1.1 vs 1.6±1.1, 0.3± 0.6 vs 0.2± 0.5 and 0.4±0.7 vs 0.3± 0.6 respectively; p<0.0001).
Figure 1. Distribution of the number of cardiovascular risk factors by gender.
BP and BP control
Mean SBP at the study visit was slightly but significantly higher in women than in men, whereas DBP was slightly but significantly lower. As a consequence, pulse pressure was significantly higher in women compared with men (). Only 1239 women (21.8%) and 1243 men (21.2%) had both SBP and DBP at goal (). The age-adjusted prevalence of uncontrolled BP, 78% in women and 79% in men, was not different. On-treatment ISH was significantly more prevalent in women than in men (30% vs 27%; p<0.002) (). Both women and men with on-treatment ISH were significantly older (on average 4 years) than patients with controlled or uncontrolled diastolic/systolic-diastolic hypertension. Target BP was significantly more often present in the oldest age group (p<0.009), but without any difference between gender; a BP<140/<90 mmHg was present in 20.5%, 20.8% and 24.0% (ns) in female patients and in 18.3%, 21.1% and 23.9% (p<0.05) in male patients aged respectively <50, 50–79 and ≥80 years. Overall BP control was similar in patients with and without diabetes (20.2% and 21.1%, respectively), for both gender (for female and male patients 19.9% and 20.4%, and 21.4% and 20.8%, respectively).
Figure 2. Distribution of blood pressure (a) in men; (b) in women. Systolic and diastolic blood pressure (BP) of the 11,562 treated hypertensive patients. Lines represent higher limit of the target BP range. Percentages in margin indicate the proportion of individuals falling above and below the limit. Percentages in the graph indicate the proportion of individuals in a given quadrant.
The stepwise multiple logistic regression analysis () showed that gender was not associated with BP control [OR for male vs female sex, 1.026 (95% CI 0.942–1.117)], even when adjusted for age, BP, BMI, diabetes, abdominal obesity, smoking and the number of antihypertensive drugs [OR, 1.103 (95% CI 0.872–1.396)].
Table II. Factors related to blood pressure control according to gender.
Use of antihypertensive medications – Lifestyle modifications
Women were treated with slightly but significantly more antihypertensive drugs than men (1.7± 0.9 vs 1.5± 0.9, p<0.0001). Both women and men with their BP at goal were treated with 1.7±0.8 antihypertensive drug classes, whereas women not at goal received 1.6 ±0.9 and men 1.5± 0.9 antihypertensive drugs (p<0.0001). Respectively, 46.1% and 49.2% of women and men were treated with antihypertensive monotherapy, and 34.7% of women and 32.1% of men received two antihypertensive drug classes. The remainder took three or more different antihypertensive drug classes (p=0.0009).
Beta-blockers were the most frequently prescribed antihypertensive agents both in men and in women, followed by diuretics, calcium-channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) (). This distribution was present in all age groups, except in the oldest one, in which diuretics became the most frequently prescribed drugs in both gender (53% in women and 39% in men, p<0.0001). Beta-blockers (46% and 44%, ns), and ARBs (21% and 20%, ns) were equally prescribed in women and men, whereas diuretics were significantly more (45% and 36.5%, p<0.0001) and CCB (27% and 29%, p<0.003) and ACEI (20.5% and 22.5%, p<0.02) significantly less frequently used in women than in men.
Figure 3. Antihypertensive drug classes in men and women. *p<0.0001, **p<0.003, ***p<0.02. BB, beta-blockers; Diur, diuretics; CCB, calcium-channel blockers; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor antagonists.
Approximately 59% of both women and men reported to follow a salt-restricting diet, and 36% of them had decreased fat intake following previous recommendations of their physician. Significantly more men than women had stopped smoking (35% vs 15%, p<0.0001), had lost weight (46% vs 44%, p<0.02), had decreased alcohol consumption (31% vs 10%, p<0.0001) and had increased physical activity (48% vs 42%, p<0.0001), whereas significantly more women than men had increased daily intake of fruit and vegetables (29% vs 26%, p<0.0001).
Treatment adaptation
In both women and men, antihypertensive treatment remained unchanged in 39.2% of the cases. The main reason for not intensifying treatment despite not achieving BP target was the perception of the physicians that BP was controlled (142± 9/83±7 mmHg) (24%) or almost at target (147±9/85±8 mmHg) (8%). No difference according to gender was observed. Both female and male patients who did not have their treatment changed received slightly but significantly more antihypertensive drug classes than those who did have their treatment changed (1.8±0.9 vs 1.6± 0.8 for women and 1.7±0.9 vs 1.5 ±0.8 for men, p<0.0001). Patients who remained on the same antihypertensive treatment were slightly but significantly younger (on average 2 years) and less obese (BMI 0.5–0.7 kg/m2 lower; p<0.0001) than patients who had their treatment adjusted, irrespective of gender.
Discussion
In the present sub-analysis of the I-inSyst survey, no gender difference in overall BP control (<140/<90 mmHg) among treated hypertensive patients was observed. Our results are in line with those find by others showing no gender difference in BP control (Citation17–23), but are in contrast with other reports showing that women with hypertension are more (Citation24–29) or less likely than men to meet BP control (Citation1,Citation17,Citation30–37).
In line with the results of other surveys, women had a lower mean DBP than men and a higher SBP, which is a stronger predictor of CV and renal disease than DBP (Citation18,Citation19,Citation30,Citation37–39). Sex-specific hemodynamic characteristics and the influence of sex hormones have been suggested to account for some of the differences between women and men, increasing e.g. the incidence of ISH and augmenting pulse pressure in elderly women (Citation40–43). The latter may explain why CVDs have become the major cause of death in women after menopause.
Although the majority of our patients had uncontrolled BP, half of them, more women than men, were treated with antihypertensive monotherapy. Despite being well established that the majority of the hypertensive population need combination therapy to achieve goal BP, 44% of English patients on treatment for hypertension were, at the same time of our survey, also on only one agent (Citation11,Citation44). The type of antihypertensive drug class varied significantly according to gender. Diuretics, in monotherapy as well as in combination therapy, were significantly more frequently prescribed in women than in men, whereas CCB and ACEI were significantly less used. This finding is in line with previous data (Citation1,Citation18,Citation30,Citation34,Citation36,Citation37,Citation45–47) and may partly be explained as a consequence of daily practicing following local authorities’ guidelines, promoting diuretics as the first-line drug. On the other hand, the different prescription pattern of antihypertensive drugs may in part reflect the coexistence of other conditions that are considered “compelling indications” (Citation11), e.g. more women than men suffer from chronic oedema of the legs of venous origin, which is a relative contra-indication for using CCBs. While the Blood Pressure Lowering Treatment Trialists’ Cooperation has found that all classical BP lowering regimens provide broadly similar protection against major CV events in both men and women (Citation48), ACEI have been reported to be less effective and induce more side-effects in women than in men (Citation38,Citation39). When ACEI and ARB were considered one class, i.e. agents that block the renin–angiotensin–aldosterone system, they became, like in other countries, the most frequently prescribed drug class (Citation21).
The present study also emphasized a significant difference in clinical profile following gender. In line with the findings of Banegas et al. (Citation18), but in contrast with those of Ong et al. (Citation19), treated hypertensive women in Belgium tended, despite their older age, to have less CV risk factors than men, with the exception of diabetes. The higher prevalence of diabetes in these women might be a consequence of the greater use of the combination diuretic-beta blocker. Indeed more incident patients with diabetes have been diagnosed in clinical trials with diuretics and/or beta-blockers (Citation49). The higher prevalence of diabetes in women may have important consequences, as patients with diabetes have a higher risk of all-cause and CVD mortality than those without diabetes (Citation50). The high prevalence of weight excess and abdominal obesity in the studied patients is alarming, as both are well known risk factors for hypertension and for excess CV morbidity and mortality (Citation14). Moreover, in the Epic-Norfolk study, women with high central obesity were 20% more likely to develop coronary heart disease compared with their male counterparts (Citation51).
Different clinical factors in women than in men were associated with BP control. Age and duration of hypertension were positively associated with BP control in men, but not in women. At least at older age, aging has been reported to be a risk factor for uncontrolled BP, especially in women (Citation1,Citation33,Citation34,Citation52). In contrast with the results of Ong et al. (Citation19), but in line with the results of Banegas et al. (Citation18), smoking was associated with less BP control in men only. Gender differences in BP values associated with smoking have also been observed in epidemiological surveys, and may be explained in part by differential confounding effects of BMI and alcohol intake (Citation53). The presence of LVH and peripheral artery disease was associated with less BP control in women, while a history of cerebrovascular disease in men and of coronary artery disease in both women and men was associated with more BP control. Although the presence of subclinical organ damage and established CVD are likely to be the consequence rather than the cause of differences in BP control, their presence may influence physicians’ decision making and consequently BP control. The number of antihypertensive drugs was associated with better BP control in both genders, emphasizing the need for combination therapy.
In spite of poor BP control, the physicians did not intensify treatment in 39% of cases, irrespective of gender, and mainly because they were satisfied with a near-normal BP. Therapeutic inertia is indeed a recognized barrier to effective care (Citation54). A comparable prevalence rate of therapeutic inertia was recently reported by Gil-Guillén et al. (Citation55), and no gender difference in initiation of new therapy for patients with uncontrolled hypertension was also found by Keyhani et al. (Citation34).
The limitations of the present study are those inherent to observational studies involving voluntary participating physicians. However, we believe that this does not affect the main objective of this sub-analysis, i.e. the evaluation of BP control according to gender. Unfortunately, we do not have data on contraceptive pill use, menopausal state and the use of hormonal substitution therapy, because the survey was not intended to record these. The strength of this survey is that it includes a large number of unselected and consecutively enrolled patients across all ages and both sexes from a large number of general physicians throughout Belgium, providing a realistic estimate of BP control, and treatment of the hypertensive population in general practice.
In conclusion, the present study showed that there was no difference in overall BP control between treated hypertensive women and men. However, BP control was associated with different clinical characteristics according to gender. An increased knowledge of the gender-specific risk for uncontrolled BP and hence for CVD should lead to improved management of hypertension. This is of utmost importance, since elderly women represent a growing subset of the population with a higher prevalence of hypertension and a high risk of hypertension-related CVD. As almost half of the women were treated with monotherapy, there is room for improvement using more combinations of well-tolerated antihypertensive drugs. Furthermore, successful treatment of hypertension also implies adherence of physicians to the guidelines targeting for optimal SBP and DBP control, while patients should comply with antihypertensive treatment and adhere to lifestyle modifications.
Acknowledgement
The survey was supported by Bristol-Myers Squibb and Sanofi-Aventis. The authors gratefully acknowledge the dedicated collaboration of the many general physicians and Mrs Nadia Fenners for the secretarial assistance.
Declaration of interest: No conflict of interest.
References
- Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum. Current outcomes and control in the community. JAMA. 2005;294:466–472.
- Banks AD. Women and heart disease: Missed opportunities. J Midwifery Women's Health. 2008;53:430–439.
- Rayner M, Allender S, Scarborough P for the British Heart Foundation Health Promotion Research Group. Cardiovascular disease in Europe. Eur J Cardiovasc Prev Rehabil. 2009;16 Suppl 2:S43–S47.
- Hayes SN. Preventing cardiovascular disease in women. Am Fam Physician. 2006;74:1331–1340.
- He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, . Major causes of death among men and women in China. N Engl J Med. 2005;353:1124–1134.
- Mosca L, Linfante AH, Benjamin EJ, Berra K, Hayes SN, Walsh BW, . National study of physician awareness and adherence to cardiovascular disease prevention guidelines. Circulation. 2005;111:499–510.
- Ezzati M, Oza S, Danaei G, Murray CJL. Trends and cardiovascular mortality effects of state-level blood pressure and uncontrolled hypertension in the United States. Circulation. 2008;117:905–914.
- Mancia G, Laurent S, Agabati-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, . Reappraisal of European guidelines on hypertension management: A European Society of Hypertension Task force document. J Hypertens. 2009;27:2121–2158.
- Kuulasmaa K, Turnstall-Pedoe H, Dobson A, Fortmann S, Sans S, Tolonen H, . Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations. Lancet. 2000;355:675–687.
- Arcucci O, de Simone G, Izzo R, Rozza F, Chinali M, Rao MA, . Association of suboptimal blood pressure control with body size and metabolic abnormalities. J Hypertens. 2007;25:2296–2300.
- Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, . 2007 Guidelines for the management of arterial hypertension. The task force for the management of arterial hypertension of the European Society of Hypertension and of the European society of cardiology. J Hypertens. 2007;25:1105–1187.
- Erdine S, Aran SN. Current status of hypertension control around the world. Clin Exp Hypertens. 2004;26:731–738.
- Van der Niepen P, Dupont A. Improved blood pressure control in elderly hypertensives in Belgium: Results of the PAPY-65 survey. Drugs & Aging 2010;27:573–588.
- Wang TJ, Vasan RS. Epidemiology of uncontrolled hypertension in the United States. Circulation. 2005;112: 1651–1662.
- Van der Niepen P, Giot C, van de Borne P. Prevalence of isolated uncontrolled systolic blood pressure among treated hypertensive patients in primary care in Belgium: Results of the I-insyst survey. J Hypertens. 2008;26:2057–2063.
- Guidelines Committee. 2003 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003; 21:1011–1053.
- Mancia G, Parati G, Borghi C, Ghironzi G, Andriani E, Marinelli, . Hypertension prevalence, awareness, control and association with metabolic abnormalities in the San Marino population: The Smooth study. J Hypertens. 2006; 24:837–843.
- Banegas JR, Segura J, de la Sierra A, Corostidi M, Rodriguez-Artalejo F, Sobrino J, . Gender differences in office and ambulatory control of hypertension. Am J Med. 2008; 121:1078–1084.
- Ong KL, Tso AWK, Lam KSL, Cheung BMY. Gender difference in blood pressure control and cardiovascular risk factors in Americans with diagnosed hypertension. Hypertension. 2008;51:1142–1148.
- Efstratopoulos AD, Voyaki SM, Baltas AA, Vratsistas FA, Kirlas DE, Kontoyannis JT, . Prevalence, awareness, treatment and control of hypertension in Hellas, Greece: The Hypertension Study in General Practice in Hellas (HYPERTENSHELL) national study. Am J Hypertens. 2006;19:53–60.
- Falaschetti E, Chaudhury M, Mindell J, Poulter N. Continued improvement in hypertension management in England. Results from the Health Survey for England 2006. Hypertension. 2009;53:480–486.
- Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment and control of hypertension in the United States, 1988–2000. JAMA. 2003;290:199–206.
- Knight EL, Bohn RL, Wang PS, Glynn RJ, Mogun H, Avorn J. Predictors of uncontrolled hypertension in ambulatory patients. Hypertension. 2001;38:809–814.
- Hyman DJ, Pavlik VN. Characteristics of patients with uncontrolled hypertension in the United States. N Engl J Med. 2001;345:479–486.
- Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, . Prevalence of hypertension in the US adult population: Results from the third National Health and Nutrition Examination Survey, 1988–1991. Hypertension. 1995;25:305–313.
- Marques-Vidal P, Arveiler D, Amouyel P, Bingham A, Ferrières J. Sex differences in awareness and control of hypertension. J Hypertens. 1997;15:1205–1210.
- Ornstein SM, Nietert PJ, Dickerson LM. Hypertension management and control in primary care: A study of 20 practices in 14 states. Pharmacotherapy. 2004;24:500–507.
- Pereira M, Lunet N, Azevedo A, Barros H. Differences in prevalence, awareness, treatment and control of hypertension between developing and developed countries. J Hypertens. 2009;27:963–975.
- Stockwell DH, Madhaven S, Cohen H, Gibson G, Alderman MH. The determinants of hypertension awareness, treatment, and control in an insured population. Am J Public Health. 1994;84:1768–1774.
- Journath G, Hellenius ML, Petersson U, Theobald H, Nilsson PM; Hyper-Q Study Group Sweden. Sex differences in risk factor control of treated hypertensives: A national primary healthcare-based study in Sweden. Eur J Cardiovasc Prev Rehabil. 2008;15:258–262.
- Alexander M, Tekawa I, Hunkeler E, Fireman B, Rowell R, Selby JV, . Evaluating hypertension control in a managed care setting. Arch Intern Med. 1999;159:2673–2677.
- Majernick TG, Zacker C, Madden NA, Belletti DA, Arcona S. Correlates of hypertension control in a primary care setting. Am J Hypertens. 2004;17:915–920.
- Ostchega Y, Dillon CF, Hughes JP, Carroll M, Yoon S. Trends in hypertension prevalence, awareness, treatment and control in older U.S. adults: Data from the National Health and Nutrition Examination Survey 1988 to 2004. J Am Geriatr Soc. 2007;55:1056–1065.
- Keyhani S, Scobie JV, Hebert PL, McLaughlin MA. Gender disparities in blood pressure control and cardiovascular care in a national sample of ambulatory care visits. Hypertension. 2008;51:1149–1155.
- Barrios V, Escobar C, Bertomeu V, Murga N, de Pablo C, Calderón A. Sex differences in the hypertensive population with chronic ischemic heart disease. J Clin Hypertens. 2008;10;779–786.
- Gu Q, Burt VL, , Paulose-RamDillon CF. Gender differences in hypertension treatment, drug utilization patterns, and blood pressure control among US adults with hypertension: Data from the National Health and Nutrition Examination Survey 1999–2004. Am J Hypertens. 2008;21:789–798.
- Thoenes M, Neuberger HR, Volpe M, Khan BV, Kirch W, Böhm M. Antihypertensive drug therapy and blood pressure control in men and women: An international perspective. J Hum Hypertens. 2010;24:336–344.
- Regitz-Zagrosek V. Therapeutic implications of the gender-specific aspects of cardiovascular disease. Nat Rev Drug Discov. 2006;5:425–438.
- Samad Z, Wang TY, Frazier CG, Shah SH, Dolor RJ, Newby LK. Closing the gap: Treating hypertension in women. Cardiol Rev. 2008;16:305–313.
- Arain FA, Kuniyoshi FH, Abdalrhim AD, Miller VM. Sex/gender Medicine – The biological basis for personalized care in cardiovascular medicine. Circ J. 2009;73:1774–1782.
- Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age specific relevance of usual blood pressure to vascular mortality: A meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–1913.
- Staessen J, Gasowski J, Wang J, Thijs L, Hond E, Boissel J, . Risks of untreated and treated isolated systolic hypertension in the elderly: Meta-analysis of outcome trials. Lancet. 2000;355:865–872.
- Fu Q, Levine BJ. Hypertension and antihypertensive therapy in elderly women: How much do we really know? Hypertension. 2006;47:323–324.
- Primatesta P, Poulter NR. Improvement in hypertension management in England: Results from the Health Survey for England 2003. J Hypertens. 2006;24:1187–1192.
- Klungel OH, de Boer A, Paes AH, Seidell JC, Bakker A. Sex differences in antihypertensive drug use: Determinants of the choice of medication for hypertension. J Hypertens. 1998;16:1545–1553.
- Nilsson PM, Journath G, Palm K, Viigimaa M. Risk factor control in treated hypertensives from Estonia and Sweden. Why the difference? Blood Press. 2007;16:301–304.
- Nieburg I, Kahan T. Cardiovascular risk factors are not treated to target in hypertensive patients in primary care. Blood Press. 2010;19:176–181.
- Turnbull F, Woodward M, Neal B, Barzi F, Ninomiya T, Chalmers J, . Do men and women respond differently to blood pressure-lowering treatment? Results of prospectively designed overviews of randomized trials. Eur Heart J. 2008;29:2669–2680.
- Lam SK, Owen A. Incident diabetes in clinical trials of antihypertensive drugs. Lancet. 2007;369:1513–1514.
- Preis SR, Hwang S-J, Coady S, Pencina MJ, D'Agostino RB, Savage PJ, . Trends in all-cause and cardiovascular disease mortality among women and men with and without diabetes mellitus in the Framingham Heart Study, 1950 to 2005. Circulation. 2009;119:1728–1735.
- Canoy D, Boekholdt SM, Wareham N, Luben R, Welch A, Bingham S, . Body fat distribution and risk of coronary heart disease in men and women in the European Prospective Investigation Into Cancer and Nutrition in Norfolk cohort: A population-based prospective study. Circulation. 2007; 116:2933–2943.
- Cutler JA, Sorlie PD, Wolz M, Thom T, Fields LE, Roccella EJ. Trends in hypertension prevalence, awareness, treatment and control rates in United States adults between 1988–1994 and 1999–2004. Hypertension. 2008;52:818–827.
- Primatesta P, Falaschetti E, Gupta S, Marmot MG, Poulter NR. Association between smoking and blood pressure. Evidence from the Health Survey for England. Hypertension. 2001;37:187–193.
- Okonofua EC, Simpson KN, Jesri A, Rehman SU, Durkalski VL, Egan BM. Therapeutic inertia is an impediment to achieving the healthy people 2010 blood pressure control goals. Hypertension. 2006;47:345–51.
- Gil-Guillén V, Orozco-Beltran D, Pérez RP, Alfonso JL, Rédon J, Pertusa-Martínez S, . Clinical inertia in diagnosis and treatment of hypertension in primary care: Quantification and associated factors. Blood Press. 2010;19:3–10.