Hypertension and Its Treatment in Postmenopausal Women
Baseline Data from the Women’s Health Initiative
Abstract—Little is known about the patterns of treatment and adequacy of blood pressure control in older women. The Women’s Health Initiative, a 40-center national study of risk factors and prevention of heart disease, breast and colorectal cancer, and osteoporosis in postmenopausal women, provides a unique opportunity to examine these issues in the largest, multiethnic, best-characterized such cohort. Baseline data from the initial 98 705 women, aged 50 to 79 years, enrolled were analyzed to relate prevalence, treatment, and control of hypertension to demographic, clinical, and risk-factor covariates, and logistic regression analyses were performed to estimate odds ratios after adjusting for multiple potential confounders. Overall, 37.8% of the women had hypertension, which is defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg or being on medication for high blood pressure; 64.3% were treated with drugs, and blood pressure was controlled in only 36.1% of the hypertensive women, with lower rates of control in the oldest group. After adjustment for multiple covariates, current hormone users had higher prevalence than did nonusers (odds ratio 1.25). Hypertensive women had more comorbid conditions than did nonhypertensive women, and women with comorbidities were more likely to be treated pharmacologically. Diuretics were used by 44.3% of hypertensives either as monotherapy or in combination with other drug classes. As monotherapy, calcium channel blockers were used in 16%, angiotensin-converting enzyme inhibitors in 14%, β-blockers in 9%, and diuretics in 14% of the hypertensive women. Diuretics as monotherapy were associated with better blood pressure control than any of the other drug classes as monotherapy. In conclusion, hypertension in older women is not being treated aggressively enough because a large proportion, especially those most at risk for stroke and heart disease by virtue of age, does not have sufficient blood pressure control.
Hypertension is a major risk factor for stroke and heart disease among both men and women. Although compared with men, women aged <55 years tend to have lower prevalence rates of hypertension, women aged 55 to 74 years have similar rates, and those aged >75 years have higher rates. Blacks have higher rates of hypertension than do whites for both genders1 Control of hypertension has been shown to reduce the risk of stroke or death in older as well as in younger persons and in those with stage I (or mild) hypertension.2 3 4 Nevertheless, as reported in the 6th Joint National Committee (JNC) Report in 1997, data from the National Health and Nutrition Examination Survey (NHANES), Phase II, for 1991 to 1994 indicate that only 54% of hypertensives were under treatment and that only 27% of hypertensives had their hypertension under control among those aged 18 to 74 years.5 Treatment and control rates are worse for those >75 years. However, little is known about the differences in prevalence, treatment, and control rates among postmenopausal women in various demographic and clinical subgroups. In both the 5th and the 6th JNC Reports,1 5 diuretics and β-blockers are suggested as first-line drugs in uncomplicated hypertension; calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors are also listed as first-line drugs for certain indications.1 Nevertheless, there continues to be disagreement with regard to the type of drugs to be used as initial therapy. Some data suggest that calcium channel blockers may be associated with an excess of morbidity and mortality,6 7 although a recent report indicated benefit for those aged >60 years with isolated systolic hypertension.8 The pattern of use of antihypertensive drugs is not known among older women in different race/ethnic groups, nor are the drug use patterns known in relation to comorbid conditions, such as diabetes, hypercholesterolemia, heart failure, and obesity.
The present study describes factors associated with the prevalence, treatment, and control of hypertension as well as the use of specific classes of antihypertensive drugs in older women enrolled in the 40 centers of the Women’s Health Initiative (WHI) across the United States. WHI is a multicenter study of US women aged 50 to 79 years consisting of overlapping clinical trials (CTs) and an observational study (OS). The CT component tests 3 interventions (hormone replacement therapy, a low fat diet, and calcium and vitamin D supplements) on multiple end points, including cardiovascular disease, cancer, and osteoporotic fractures. The OS, conducted in parallel, is a long-term prospective cohort study to identify and assess the impact of biological, lifestyle, biochemical, and genetic factors on the risk of heart disease, cancer, osteoporosis, and other major health events. The present report uses baseline data obtained from the initial 98 705 women enrolled (43 427 in the CTs and 55 278 in the OS) from September 1993 through the end of February 1997.
The questions addressed in this report are as follows: (1) What is the prevalence of hypertension among different subgroups of postmenopausal women? (2) How is hypertension treated in older women in the late 1990s, and how does the treatment correspond to the national guidelines promulgated by the JNC on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure? (3) How adequately is blood pressure controlled in postmenopausal women?
Women aged 50 to 79 years, who gave written informed consent, were recruited into the WHI at 40 clinical centers in the United States, mostly through mass mailings to age-eligible women from large mailing lists, such as voter registration, driver’s license, and Health Care Financing Administration (HCFA) or other insurance lists. Recruitment of minorities and older women was a particular study objective. Details of the WHI design are reported elsewhere.9 Women were either specifically recruited for the OS or entered it because they were ineligible or unwilling to be randomized into the CTs. Exclusions were participation in other randomized trials, predicted survival of <3 years, alcoholism, drug dependency, mental illness, dementia, or other conditions making them unable to participate in the study. Women with systolic blood pressure (SBP) >200 mm Hg or diastolic blood pressure (DBP) >105 mm Hg were excluded from the CTs and were told to see their physician but were eligible for the OS. The results reported in the present study combine baseline data from women in all WHI components. Of the 98 705 women enrolled, 7411 were excluded from analyses because of early changes in the data collection forms so that the definition of hypertension could not be strictly applied. An additional 539 women had missing data on hypertension status. Thus, 90 755 women remained whose hypertension and treatment status could be determined.
Blood pressure was measured at the first screening clinic visit by certified staff with the use of standardized procedures and instruments; it was measured in the right arm with a conventional mercury sphygmomanometer after the participant was seated and had rested for 5 minutes before the blood was drawn or a minimum of 30 minutes after the blood was drawn. The cuff, of appropriate size based on arm measurement, was inflated to 30 mm Hg above palpated SBP. SBP was defined as the pressure level at which the first of ≥2 knocking sounds occurred in appropriate rhythm. DBP was phase V Korotkoff value (disappearance of sound). The average of 2 readings, obtained at least 30 seconds apart, was used for analysis.
Women were asked to bring all of their prescription medications, currently used over-the-counter medications, and vitamins and minerals in their original bottles to the baseline visit. The product or generic name, dosage, form, and strength of the medications were transcribed from the label into the study computer database and matched to the corresponding item in a pharmacy database: the Master Drug Data Base (Medi-Span). This database includes drug names (both brand and generic), national drug codes, and a therapeutic class code provided by the American Hospital Formulary Service for both prescription and over-the-counter products. The study-wide computer system was updated approximately every quarter with a new pharmacy database to ensure completeness of the list of available products.
Hypertensives were defined as those who reported that they were told by a doctor that they had high blood pressure and that they were currently taking medicine for their hypertension and/or they had a clinic blood pressure of SBP ≥140 mm Hg and/or DBP ≥90 mm Hg. Women who reported a diagnosis of hypertension but did not report that they were currently on blood pressure medications and did not have elevated pressures at the visit were classified as unconfirmed hypertensives and were omitted from analyses of hypertensives. Those having neither a physician diagnosis nor elevated pressures constituted the remainder and were considered normotensives. Treated hypertensives were those among the hypertensives who responded yes to the following question: Do you now take pills for high blood pressure? Controlled hypertensives were those whose clinic blood pressures were SBP <140 and DBP <90 mm Hg. Over 85% of women who reported taking drugs for hypertension provided medications at their baseline visit that fell into one of the drug class categories. Past smokers were those who had ever smoked at least 100 cigarettes but did not currently smoke. Past drinkers were those who had ever had at least 12 alcoholic beverages in their life but did not currently drink. Current drinkers were further classified by current alcohol intake, based on the sum of beer, wine, and liquor intake adjusted for portion size from a semiquantitative food frequency questionnaire. Physical activity was assessed by questions regarding the frequency and duration of walking at various intensities and 3 other types of recreational activity classified by intensity (strenuous, moderate, or light). These data were summarized into episodes per week of moderate or strenuous activity (as defined by a MET score of at least 4.0 as indicated by Ainsworth et al10 ) of at least 20-minute duration. Women reporting some recreational activity but of shorter duration and/or lesser intensity were classified as those having “some activity.”
Other cardiovascular disease risk factors included history of myocardial infarction (MI) in a first-degree relative, diabetes, obesity, and hypercholesterolemia. Women were considered overweight if their body mass index (BMI) exceeded 27.3 kg/m2. Pharmacotherapy for hyperlipidemia was defined by self-report of current use of medications for high cholesterol. Blood samples drawn at baseline were frozen and sent to a central biological repository for future nested case-control studies, and blood lipids were not analyzed at baseline. Diabetes was defined as a physician diagnosis plus self-reported use of insulin or oral medication. Other comorbid conditions (MI, stroke, and heart failure) were defined on the basis of the participant’s report of physician diagnosis.
The rates of prevalence, treatment, and control of hypertension are presented for levels of the categorical variables of interest. For bivariate analyses, women with missing values for other variables were omitted only for the corresponding variable. Because these results are primarily descriptive in nature and because the large sample size would result in statistical significance for minor associations, statistical levels of significance are not generally shown.
Logistic regression analyses, with adjustment for covariates, were conducted to describe factors related to prevalence, treatment, and control of hypertension. Unconfirmed hypertensives were excluded from these analyses. Independent variables were demographic factors, health behaviors, comorbid conditions, and other cardiovascular disease risk factors. Prevalence models were run on the entire sample (excluding unconfirmed hypertensives). Regression models to determine factors associated with treatment were run on the sample of hypertensive women, excluding those with missing data on treatment. Models to explore the factors associated with control of hypertension among the hypertensive women (excluding those with missing data on control) also included drugs used from the medication inventory.
Age, BMI, and waist-to-hip ratio were modeled as continuous variables. For BMI, a second-order term was included. Indicator variables for clinical center were included to account for site-specific variation (not shown). Missing values for categorical variables were modeled as an additional level for each variable (not shown). Participants with missing values for the continuous values were omitted from the multivariate analyses (n=962 for the prevalence model). The results are presented as odds ratios (ORs), adjusted for covariates, with 95% CIs and 2-sided probability values based on Wald statistics.11 All analyses were conducted by use of Statistical Analysis Software (SAS Institute).
Baseline characteristics of the cohort (not shown) indicate that the cohort was 84% white, 9% black, 3% Hispanic (predominantly Mexican), and 4% other. Forty percent were aged 50 to 59 years, 40% were aged 60 to 69 years, and 20% were aged 70 to 79 years. Seventy-seven percent had some education beyond high school, with 40% having a college degree or higher. Thirty-six percent had a family income of ≥$50 000. Approximately 50% never smoked, and only 7% were current smokers. Forty-two percent were current hormone users; 46% were overweight (with a BMI >27.3 kg/m2).
The overall prevalence of hypertension was 37.8% (Table 1⇓). An additional 4.0% reported that they had hypertension but were not on medication and had normal clinic blood pressures. This group of women was not included among those defined as hypertensives. Among the 34 339 hypertensives, 64.3% reported current use of antihypertensive drugs. However, only 36.1% of the hypertensives had their blood pressures controlled to the level of SBP <140 and DBP <90 mm Hg. The mean±SD blood pressures by hypertensive status, expressed as SBP/DBP, were as follows: 117±11.5/72±7.7 mm Hg for normotensives; 125±9.7/76±7.5 for unconfirmed hypertensives; 141±16.9/81±10.3 for all hypertensives; 137±17.8/78±9.7 for all treated hypertensives; and 125±9.7/75±7.9 for controlled hypertensives. At the baseline clinic examination, 17.4% had elevations of SBP at the clinic visit, with DBP <90 and with SBP predominantly between 140 and 160 mm Hg. Some of these women were on antihypertensive treatment; thus, they do not represent true isolated systolic hypertension because some may have had pretreatment elevations of DBP. They do, however, represent a group with inadequately controlled SBP in the presence of normal DBP.
Factors Associated With Varying Prevalence Rates
Prevalence rates varied by subgroups (Table 2⇓⇓. Older women (aged 70 to 79 years) had twice the prevalence rate (53.4%) of women aged 50 to 59 years (26.7%). Prevalence was higher in blacks than in whites or in Hispanics (59.3% versus 35.5% in whites and 33.4% in Hispanics) and in those with lower socioeconomic status, as indicated by lower education and income levels.
Overall, prevalence of hypertension was substantially higher (48.0%) among the overweight (BMI >27.3) than among those not overweight (29.3%), and the same relationship held within each category of smoking status. Among the nonoverweight, prevalence essentially did not vary by smoking status, although among the overweight, there was a slightly lower prevalence in current smokers than in those who had never smoked (40.3% versus 49.6%). Alcohol consumption showed a U-shaped relationship with prevalence, with 46.2% of nondrinkers having hypertension compared with 31.6% of those who reported drinking between 1 and 7 alcoholic beverages per week and 35.6% of those drinking ≥7 alcoholic beverages per week. There was a dose-response relationship between physical activity and prevalence, ranging from 45.3% among those with no moderate or strenuous activity to 31% for those with ≥4 such episodes per week. Persons with any one of the cardiovascular risk factors of family history of MI, high cholesterol, or diabetes or a history of MI, heart failure, or stroke had markedly higher rates of hypertension than did those without such risk factors.
Current hormone users had lower prevalence (34.9%) than did those who had never used hormones (40.5%) in bivariate analyses. However, because current hormone users compared with those who had never used hormones were younger (aged 60.8 versus 63.5 years) and thinner (BMI 26.9 versus 28.8), confounding may have influenced the bivariate findings. When age, BMI, and waist-to-hip ratio were included in a logistic regression analysis, which also adjusted for education, smoking, alcohol intake, physical activity, high cholesterol, diabetes, family history of MI, and comorbid conditions, current hormone use in this cross-sectional study was associated with a 25% greater likelihood of hypertension than past use or no previous use (OR for current users versus nonusers was 1.25, 95% CI 1.21 to 1.30).
The multivariate analyses generally confirmed the findings on prevalence shown in Table 2⇑, except for hormone use, as noted above. The likelihood of hypertension, after control for the multiple covariates, increased with increasing BMI (OR per unit BMI increase was 1.17, 95% CI 1.16 to 1.19). Waist-to-hip ratio was a significantly associated with prevalence even after controlling for BMI (OR per 1 SD, which is an ≈10% increase in the ratio, was 1.20; 95% CI 1.18 to 1.22). Logistic regression models were also run for the cohort excluding those who had a history of MI, stroke, or heart failure and separately for the group who did have such a history, with similar results.
Factors Associated With Varying Rates of Treatment of Hypertension
Treatment rates did not vary by age group but did vary by race/ethnicity, with black women having the highest treatment rates (75.6%) and Hispanic women having the lowest (59.4%). There was a weak inverse relationship between treatment rates and family income, ranging from 70.8% of those with income <$10 000 to 61.0% of those with income of ≥$75 000. Women whose only insurance was Medicaid had substantially and significantly higher rates of treatment (80.8%, 95% CI 75.3 to 80.3) than did those with other types of insurance, such as prepaid private insurance (65.2%, 95% CI 64.2 to 66.2), other private insurance (63.2, 95% CI 62.1 to 64.3), or Medicare only (63.9%, 95% CI 62.1 to 65.8).
Logistic regression analyses, controlling for multiple potential confounders (not shown), indicated that among the 34 339 hypertensives, the likelihood of being on drug treatment was significantly higher for blacks than for whites (OR 1.63, 95% CI 1.49 to 1.79) and for Asians than for whites (OR 1.21, 95% CI 1.10 to 1.45). Current hormone users compared with those who had never used hormones were 26% more likely to be on drug treatment (OR 71.26, 95% CI 1.18 to 1.34), supporting the inference that current hormone users are generally more health conscious as well as being younger and thinner. Those who had seen a health care provider in the past year were 3.62 times as likely to be on drug treatment (95% CI 3.36 to 3.89) as those who had not seen a provider.
Most hypertensives were treated with only 1 class of drugs (57.6%). Two drug classes were used in 31.8% of those treated, and ≥3 classes were used in 6.4%. As monotherapy, the most commonly used drug class was calcium channel blockers, with 16.4% of treated hypertensives taking calcium channel blockers either as monotherapy and 33.5% when including combinations with another drug class, compared with 14.4% using a diuretic as monotherapy and 44.3% on diruetics overall, including combination therapy. Table 3⇑ shows use of these drug classes as monotherapy and use of multiple drug classes in different subgroups of participants. ACE inhibitors as monotherapy were more likely to be used in the younger age group of treated hypertensives than in the oldest group (16.3% versus 12.2%, respectively); monotherapy use of the other drug classes was similar across the 3 age groups. Calcium channel blockers were more likely to be used by Asians (29.9%), blacks (19.9%), and Hispanics (23.3%) than by whites (14.9%). The type of insurance did not appear to be strongly related to the type of drug class used as monotherapy, except that those on Medicaid had slightly higher rates of use of calcium channel blockers both as monotherapy and in combination with other drugs, but this may be confounded by race. Those with comorbid conditions (diabetes, history of stroke, MI, or heart failure) were substantially more likely to be treated with multiple drug classes than those without such conditions. Diabetic status was not related to the use of calcium channel blockers as monotherapy, but use of calcium channel blockers in combination with other drugs (not shown) was higher in diabetics than in nondiabetics (45.4% of insulin-dependent treated diabetics and 37.8% of non–insulin-dependent diabetics versus 32.5% of nondiabetics). β-Blocker use as monotherapy was fairly similar among those with a history of MI (11.1%) and those without such history (9.1%); however, β-blockers in combination with other drugs were more likely to be used by those with a history of MI (37.5%) than by those with no prior MI (22.8%).
Factors Associated With Varying Rates of Control of Hypertension
As shown in Table 2⇑, although older hypertensive women (aged 70 to 79 years) were as likely to be on treatment (63.2%) as the younger women (64.2%), a substantially smaller percentage of them had their blood pressures under control (29.3% versus 41.3% for the older versus younger women, respectively). These older women are most at risk for stroke and other complications of hypertension, but even among those who were on pharmacological treatment, less than half (46.4%) had their blood pressures under control compared with 64.2% of women aged 50 to 59 years on treatment (not shown), suggesting that older women may be more difficult to control and/or may not be treated as aggressively as younger postmenopausal women. In bivariate analyses, black hypertensive women had the highest rates of control. Control rates among hypertensives on Medicaid only were similar to those with prepaid or private insurance, although they were significantly higher (43.9%, 95% CI 37.0 to 50.8) than for those on Medicare only (31.6%, 95% CI 29.8 to 33.4) or for those with no insurance (30.0%, 95% CI 27.4 to 32.7). The higher rate of control among Medicaid-covered women than among Medicare-covered women may reflect age differences between these 2 groups but may also be due to the fact that Medicaid covers drugs but Medicare does not. Eighty-one percent of the Medicaid-insured hypertensive women were being pharmacologically treated compared with 64% of the Medicare-insured women (Table 2⇑).
Among those 22 096 hypertensives who were treated pharmacologically, after adjustment for multiple covariates, those less likely to have their hypertension under control were older women and all nonwhite groups (Table 4⇑). Current smokers were more likely than those who had never smoked to have their blood pressures under control (OR 1.37, 95% CI 1.21 to 1.56). Women who were heavier were more likely to be treated (not shown, OR 1.06 per unit increase in BMI), and of those treated, they were slightly more likely to be controlled (OR 1.01 per unit increase in BMI). Possibly, this implies more aggressive treatment of hypertension among the obese. Educational level, alcohol intake, activity level, having seen a heathcare provider in the past year, hyperlipidemia requiring drug treatment, hormone use, and comorbid conditions (except for diabetes) were not related to the control of hypertension among those being treated after adjustment for covariates. Of particular interest is that those who were on a β-blocker, ACE inhibitor, or calcium channel blocker as monotherapy were less likely to have their blood pressures controlled than were those on a diuretic alone, after adjustment for multiple covariates that might be related to choice of therapy. (Unadjusted control rates, not shown, were 63% of those on monotherapy with diuretics, 57% of those on monotherapy with β-blockers, 56% on ACE inhibitors, and 50% of those on calcium channel blockers.) Hypertension control was not related to the number of drug classes. Of those treated with 1 drug class, 56% had their hypertension under control; of those treated with 2 drug classes, 58% had their hypertension under control, and of those treated with ≥3 drug classes, 52% had their hypertension under control.
WHI provided an opportunity to examine factors associated with prevalence, treatment, and control of hypertension in different subgroups of a multiethnic cohort of nearly 100 000 postmenopausal women across the United States. The overall prevalence rate of hypertension was 38%, with a prevalence of 59% for black women and 36% for white women. Despite the fact that the WHI cohort is composed of volunteers who are in relatively good health, the prevalence rates are fairly close to the prevalence for this age group in NHANES III.12 13 NHANES is a national probability sample and so may be more representative of American women, but the NHANES data are based on only ≈1740 women in this age group. This WHI report is based on nearly 100 000 women ages 50 to 79 years and is the largest and best-characterized cohort of postmenopausal women, with data on the current patterns of hypertension treatment and control.
Women who were current hormone users had a higher prevalence of hypertension when controlling for age, BMI, and waist-to-hip ratio. The univariate protective effect of hormone use is confounded by these 3 variables because hypertensive hormone users were “healthier” in the sense that they were thinner and younger. After accounting for age and weight-related variables, current hormone use was associated with a greater odds of being hypertensive. This cross-sectional result differs from the effect of hormone use on hypertension found in the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial,14 which reported no significant differences from placebo in SBP or DBP change in women treated with hormones over a 3-year period. The PEPI cohort, however, was considerably younger, with ages ranging from 45 to 64 years (average age 56 years) than the WHI cohort, with ages ranging from 50 to 79 years (average age 62 years). The Hormone Therapy Replacement Clinical Trial component of WHI, to be completed in the year 2005, will address the question of the effect of hormones on the development of hypertension prospectively in these older women.
The second issue addressed in the present report concerned the patterns of treatment common in the mid and late 1990s and their correspondence to national guidelines for the treatment of hypertension. In the WHI, 64% of hypertensives were treated pharmacologically; that rate was similar to the treatment rates found in NHANES,13 with little difference by age group. Black women and those on Medicaid had higher rates of treatment. Although the numbers of women on Medicaid were small in this cohort, it should be noted that the treatment rate in this subgroup was the highest of all insurance categories (81% compared with ≈63% to 65% for those with private insurance or Medicare), suggesting that insurance coverage of drugs has a substantial impact on the percent being treated.
It is noteworthy that actual treatment patterns differ from the JNC guidelines for the treatment of uncomplicated hypertension. The JNC V1 and JNC VI5 guidelines recommend the use of diuretics and β-blockers in uncomplicated hypertensive patients. The data from WHI suggest that these guidelines are not uniformly followed for postmenopausal women, in view of the fact that the most common drug class used as monotherapy was calcium channel blockers, in 16% of treated hypertensives and the least common drug class was β-blockers in 9%. Diuretics and ACE inhibitors were used in ≈14.5% of treated hypertensives. Others have also reported the lack of effect of JNC V recommendations with regard to the drug used.15 There are several possible explanations for this discrepancy. Because only 2% of this group had a history of MI, 1% had a history of stroke, and 5% had a history of diabetes, the possibility that a large number of women in this cohort who are on monotherapy may actually have complicated hypertension seems unlikely. Another possibility is that physicians are not appropriately following guidelines, possibly because of insufficient or ineffective dissemination of these guidelines or because of countervailing influences, such as the marketing efforts of pharmaceutical companies. Finally, physicians may not be strictly adhering to guidelines for appropriate reasons, which are based on their clinical judgment about individual patients. The answer to the question of which monotherapy has most beneficial effects on heart disease outcomes awaits the results of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT),16 a randomized double-blind trial comparing 3 different antihypertensive drug classes with diuretic therapy that is being conducted among 40 000 high-risk hypertensive patients and is to be completed in the year 2002.
In hypertensive patients with diabetes, the JNC VI guidelines recommend the use of diuretics for type 2 diabetics and ACE inhibitors for type 1 diabetics.5 Diuretics were used in hypertensive patients with diabetes in 11% as monotherapy and in a total of 43% when including combination therapy. Although ACE inhibitors were commonly used in these WHI participants (16% as monotherapy and 48% and 38% including combination therapy in type 1 and 2 diabetics, respectively), so were calcium channel blockers (14% as monotherapy and 45% and 38% including combination therapy in type 1 and 2 diabetics, respectively). Several recent CTs have directly compared diuretics or ACE inhibitors with calcium channel blockers in hypertensive patients with diabetes.17 18 19 20 The Appropriate Blood Pressure Control in Diabetes (ABCD) trial,17 for instance, was stopped early because of an increased risk of cardiovascular events in hypertensive diabetic patients randomized to calcium channel blockers compared with those randomized to the ACE inhibitors (risk ratio 5.5, 95% CI 2.1 to 14.6). Another trial of the ACE inhibitor ramipril versus placebo was also stopped early with data released before the publication date because of significant and marked reductions of cardiovascular events in a broad range of high-risk patients with the use of ramipril.21 Given the results of these recent comparative trials, it is likely that ACE inhibitor use will increase.
The final issue examined was the adequacy of control of hypertension in older women. Although overall, 64% of the WHI hypertensive women were treated, only about a third were controlled. In NHANES III (1988 to 1991), data indicate that 81% of hypertensive women aged 18 to 74 years are aware of their condition, 65% are under treatment, and 38% have their hypertension under control.13 This is more than double the percentage under control in NHANES II, when only 15% of hypertensive women had blood pressures <140/90 mm Hg. Concomitantly, with the increase in control of hypertension over the last several decades, there has been a marked decrease of deaths from heart disease by ≈50% and of deaths from strokes by ≈57%. A recent report from the Framingham Heart Study22 indicated that use of antihypertensive medication increased substantially between 1950 and 1989 as well as from the 1970s to the 1980s, with a concomitant decline in left ventricular hypertrophy. Thus, there has been an improvement in the public health related to hypertension treatment and control in general, but this may not apply to older people. Although treatment and control rates among WHI women are similar to those found in NHANES III, nevertheless, two thirds of all the WHI hypertensive women had blood pressures >140/90 mm Hg, and in particular, 71% of those aged 70 to 79 years had clinic blood pressures above those levels. Even among those women who were on drug treatment, only 56% had controlled hypertension, indicating that the goal of an SBP <140 mm Hg and a DBP <90 mm Hg is not being met in half of the hypertensive older women being treated with drugs. In fact, hypertensive women who had seen a healthcare provider in the past year were 3.6 times more likely to be on drug treatment, but those treated were not significantly more likely to be controlled than those who had not seen a provider, after adjusting for multiple covariates. Inadequate control of blood pressure has also been recently reported in a population of older men who were receiving regular medical care at Veterans Affairs sites and who made frequent visits for health care.23 Fewer than 25% of these patients had blood pressures <140/90 mm Hg. The authors conclude that poor blood pressure control could not be explained by lack of access to medical care but that physicians were not treating high blood pressure sufficiently aggressively. In the JNC recommendations, target blood pressure levels are the same regardless of age, although there is some inconsistent evidence on the optimum blood pressure levels for older people.
In the WHI, monotherapy with diuretics was more strongly associated with good control of blood pressure than was monotherapy with β-blockers, calcium channel blockers, ACE inhibitors, or the use of multiple drugs. In the absence of information on pretreatment levels of blood pressure, it is possible that part of the association of diuretics with good control may represent confounding by the severity of hypertension and that those who were put on other classes of drugs were initially resistant to diuretics. Nonetheless, diuretics are known from CTs to be effective in lowering blood pressure and in preventing complications such as MI, stroke, and congestive heart failure in men and women.3 4 24 25
In conclusion, it is important to note that two thirds of older hypertensive women, who are most at risk for stroke and cardiovascular events, do not have their hypertension adequately controlled, either because they are not on drug treatment or because in spite of taking antihypertensive drugs, their blood pressure is still above recommended levels. Additionally, the guidelines for drug treatment of hypertension as recommended by the JNC on the Detection, Evaluation and Treatment of High Blood Pressure are not being widely implemented in this group with regard to goal blood pressure levels. The drug class most commonly used by WHI women as monotherapy was calcium channel blockers, although these drugs were associated with a lower likelihood of control when used as monotherapy than was monotherapy with diuretics. The question of which drug classes offer the most benefit for older hypertensive women is as yet unanswered.
Short List of WHI Investigators
National Heart, Lung, and Blood Institute, Bethesda, Md: Carolyn K. Clifford, Suzanne S. Hurd, Joan A. McGowan, Linda Pottern, and Jacques E. Rossouw.
Clinical Coordinating Centers
Fred Hutchinson Cancer Research Center, Seattle, Wash: Ross Prentice, Maureen Henderson, Garnet Anderson, Andrea LaCroix, and Anne McTiernan; Bowman Gray School of Medicine, Winston-Salem, NC: Curt Furberg and Pentti Rautaharju; Medical Research Labs, Highland Heights, Ky: Evan Stein; University of California at San Francisco: Steven Cummings; University of Minnesota, Minneapolis: John Himes; and University of Washington, Seattle: Bruce Psaty.
Albert Einstein College of Medicine, Bronx, NY: Sylvia Wassertheil-Smoller; Baylor College of Medicine, Houston, Tex: Jennifer Hays; Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass: JoAnn Manson; Brown University, Providence, RI: AnnLouise R. Assaf; Emory University, Atlanta, Ga: Nelson Watts; Fred Hutchinson Cancer Research Center, Seattle, Wash: Shirley Beresford; George Washington University Medical Center, Washington, DC: Judith Hsia; Harbor-UCLA Research and Education Institute, Torrance, Calif: Rowan Chlebowski; Kaiser Permanente Center for Health Research, Portland, Ore: Barbara Valanis; Kaiser Permanente Division of Research, Oakland, Calif: Bette Caan; Medical College of Wisconsin, Milwaukee: Jane Morley Kotchen; Medlantic Research Institute, Washington, DC: Barbara V. Howard; Northwestern University, Chicago/Evanston, Ill: Philip Greenland; Cook County Hospital, Rush-Presbyterian St. Luke’s Medical Center, Chicago, Ill: Henry Black; Stanford Center for Research in Disease Prevention, Stanford University, Stanford, Calif: Marcia L. Stefanick; State University of New York at Stony Brook: Dorothy Lane; The Ohio State University, Columbus: Rebecca Jackson; University of Alabama at Birmingham: Albert Oberman; University of Arizona, Tucson/Phoenix: Tamsen Bassford; University at Buffalo, Buffalo, NY: Maurizio Trevisan; University of California at Davis, Sacramento: John Robbins; University of California at Irvine, Orange: Frank Meyskens; University of California at Los Angeles: Howard Judd; University of California at San Diego, La Jolla/Chula Vista: Robert D. Langer; University of Cincinnati, Cincinnati, Ohio: James Liu; University of Florida, Gainesville/Jacksonville: Marian Limacher; University of Hawaii, Honolulu: David Curb; University of Iowa, Iowa City/Davenport: Robert Wallace; University of Massachusetts, Worcester: Judith Ockene; University of Medicine and Dentistry of New Jersey, Newark: Norman Lasser; University of Miami, Miami, Fla: Mary Jo O’Sullivan; University of Minnesota, Minneapolis: Richard Grimm; University of Nevada, Reno: Sandra Daugherty; University of North Carolina, Chapel Hill: Gerardo Heiss; University of Pittsburgh, Pittsburgh, Pa: Lewis Kuller; University of Tennessee, Memphis: Karen C. Johnson; University of Texas Health Science Center, San Antonio: Robert Schenken; University of Wisconsin, Madison: Catherine Allen; Wake Forest University School of Medicine, Winston-Salem, NC: Electra Paskett; and Wayne State University School of Medicine/Hutzel Hospital, Detroit, Mich: Susan Hendrix.
This study was supported by grant NO1-WH-4-2119 from the National Institutes of Health, Department of Health and Human Services. We wish to acknowledge all WHI Centers and their Principal Investigators for their participation in this research.
- Received January 11, 2000.
- Revision received February 17, 2000.
- Accepted March 28, 2000.
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