The case patient is a 53-year-old African American woman with a 3-year history of intermittent elevated blood pressure during routine physical examinations. She has attempted with moderate success to follow a low-salt diet for 6 months. She is married with 2 adult children and is employed as an insurance claims agent. She denies alcohol or tobacco use.
The patient's medical history includes degenerative joint disease in her knees and ankles, hypothyroidism, and perimenopausal symptoms. She is currently taking ibuprofen as needed for the joint pain, as well as levothyroxine and over-the-counter soy estrogen as treatment for the hypothyroidism and perimenopausal symptoms.
Weight: 175 lb
Heart rate: 72 beats/min
Blood pressure: 135/85 mm Hg (seated) (her last 6 office measurements averaged 138/82 mm Hg)
Waist circumference: 42 inches
Pulses: Full at all sites
Thyroid: Not palpable
Heart: Normal rate and rhythm with no murmurs or gallops
Range of motion: Decreased due to pain at knees
Electrocardiogram: Normal sinus rhythm; 72 beats/min; left anterior hemiblock pattern with no Q waves
Chemistry panel: Creatinine 1.5 mg/dL(1.2 mg/dL in 2000); otherwise within normal limits
Complete blood count: Within normal limits
Thyroid-stimulating hormone: Within normal limits
Lipid panel: Within normal limits (low-density lipoprotein cholesterol [LDL-C], 120 mg/dL)
Prehypertension is a designation to identify those individuals at high risk for developing hypertension, so that both patients and clinicians are aware of the risk and can intervene and prevent or delay the progression to hypertension. According to the JNC-7, patients who are prehypertensive should not be started on drug therapy (except for those patients who also have diabetes mellitus or renal disease and in whom lifestyle modification failed to reduce their blood pressure to ≤ 130/80 mm Hg). Otherwise healthy patients should be advised to practice lifestyle modification to reduce their risk of developing hypertension in the future.
The JNC-7 introduced the term prehypertension to designate individuals whose SBP levels are between 120 and 139 mm Hg and whose DBP levels are between 80 and 89 mm Hg. The decision to establish the new blood pressure category was based on a number of factors. Several studies have indicated that in most societies, blood pressure increases with age. Furthermore, studies have shown that the incidence of cardiovascular disease (CVD) and stroke increases progressively as blood pressure levels rise.
In patients older than 50 years, SBP of > 140 mm Hg is a more important CVD risk factor than DBP.
A large body of evidence has shown that SBP represents a major risk factor for CVD. Changing patterns of blood pressure occur with increasing age (Figure 1). Systolic blood pressure rises throughout life, whereas DBP rises until age 50 and then levels off. Prior to 50 years of age, DBP represents a more potent cardiovascular risk factor than SBP; however, after 50 years of age, SBP is more important.
Figure 1. Changes in systolic and diastolic blood pressure with age. From Chobanian, Hypertension., 2003.
Released in 2003, JNC-7 includes several changes from the previous report (JNC-6) released in 1997. Aside from designating the term prehypertension, JNC-7 also combined stages 2 and 3 of hypertension into a single category (stage 2 hypertension).
The development of JNC-7 was prompted by important new evidence from observational and clinical trials of hypertension management that arose since the previous report was released. The newest edition simplifies the classification of blood pressure levels to maximize guideline implementation.
Normal blood pressure is defined as SBP < 120 mm Hg and DBP < 80 mm Hg; SBP of 120 to 139 mm Hg or DBP of 80 to 89 mm Hg is defined as prehypertension in JNC-7. The low-end threshold for prehypertension is lower than the JNC-6 designation of high-normal blood pressure (ie, SBP/DBP: 130/85, JNC-6).
|JNC-6 Category||SBP/DBP||JNC-7 Category|
|Stage 1||140-159/90-99||Stage 1|
|Stage 2||160-179/100-109||Stage 2|
|State 3||≥ 180/110||Stage 2|
DBP: diastolic blood pressure; SBP: systolic blood pressure; JNC: Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
From Chobanian, Hypertension., 2003.
A 2004 study by Greenlund and associates reported that people with prehypertension had a higher prevalence of other risk factors for stroke and heart disease, including hypercholesterolemia, obesity, and diabetes mellitus, than did people with normal blood pressure levels. Furthermore, the number of people with at least 1 other risk factor for heart disease or stroke (cholesterol level ≥ 240 mg/dL [≥ 6.21 mmol/L], body mass index [BMI] ≥ 30 kg/m2, diabetes mellitus, or current smoking) was greater among those with prehypertension than among those with normal blood pressure; the number was highest among those with hypertension. Nearly two thirds of the prehypertensive patients and three quarters of the hypertensive patients had at least 1 other risk factor for heart disease or stroke.
Approximately 25% of adults in this study had none of the 5 major risk factors for heart disease and stroke, including high blood pressure. Although there were no sex or race/ethnic differences in the probability of other risk factors among those with prehypertension, African Americans were more likely than whites and Mexican Americans to have hypertension at younger ages.
A 2004 study by Wang and associates that used cross-sectional analysis of national representative data found that approximately 60% of US adults (67% of men and 50% of women) had prehypertension or hypertension. In contrast to the Greenlund study, Wang's study reported that the prevalence of prehypertension was higher among men than women (40% vs 23%), but the prevalence of hypertension was similar between both sexes, which may be related to a lower awareness of hypertension among men. Furthermore, considerable ethnic-, age-, and education-related differences were observed. African Americans had the highest rate, whereas Mexican Americans had the lowest, and rates increased considerably with age.
Some groups, such as African Americans, older individuals, those in low socioeconomic-status groups, and those who are overweight, are disproportionately affected by high blood pressure. Only approximately 34% of people with high blood pressure have it controlled.[1,3]
Worldwide prevalence estimates for hypertension may be as much as 1 billion individuals, and approximately 7.1 million deaths per year may be attributable to hypertension.
The World Health Organization reports that suboptimal blood pressure (SBP >115 mm Hg) is responsible for 62% of cerebrovascular disease and 49% of ischemic heart disease, with little variation by sex. In addition, suboptimal blood pressure is the most commonly associated risk for death throughout the world.
Because people with prehypertension tend to have more adverse risk factors than those without elevated blood pressure, investigators in the Greenlund study suggested the need to further examine CVD risk and to employ more aggressive preventive strategies in patients with prehypertension. The higher prevalence of hypertension in African Americans at younger ages than in whites and Mexican Americans highlights the need for more aggressive efforts at prevention and control in this group. Obtaining a comprehensive risk-factor profile may aid healthcare professionals in assessing heart disease and stroke risk, ultimately leading to earlier intervention and better patient outcomes.
The 5 nonpharmacological treatments for prehypertension recommended by JNC-7 have been proven through clinical trials to significantly lower blood pressure, and most have been shown to prevent progression to hypertension. However, these recommendations do not apply to patients with diabetes or chronic renal disease because drug treatment is advocated in those specific populations.
The first recommended nonpharmacological treatment for prehypertension is the DASH diet, which is rich in potassium (from fruits and vegetables) and calcium (from dairy), reduced in total and saturated fat, and contains limited amounts of meats and sweets.
Weight loss is the second recommended nonpharmacological treatment for prehypertension. Extensive evidence in the literature has shown a substantial and significant blood pressure-lowering effect of weight loss. According to a study by Neter and associates, reductions in blood pressure occurred with weight loss, even without attainment of normal BMI. The meta-analysis of 25 randomized, controlled trials revealed that weight loss of 1 kg was associated with an approximate 1-mm Hg reduction in SBP and DBP in individuals with prehypertension.[5,6]
The third nonpharmacological treatment for prehypertension recommended by JNC-7 is reduced sodium intake. This recommendation is based on several epidemiologic surveys that show a consistent direct correlation between sodium intake and blood pressure. In addition, numerous human trials indicate that reducing sodium intake leads to reductions in blood pressure.
The fourth recommendation is regular physical activity. Numerous studies have found a negative correlation between habitual physical activity and the development of hypertension. This relationship has been observed in both men and women in all age groups, regardless of race.
The final nonpharmacological treatment for prehypertension recommended by JNC-7 is moderate alcohol consumption. The relationship between drinking excess amounts of alcohol and elevated blood pressure has been reported in observational studies, but results from clinical trials have been inconsistent. Overall, the evidence favors moderation of alcohol intake to currently recommended limits (2 ounces per day for men and 1 ounce per day for women) in the management of prehypertension.
Lifestyle modifications reduce blood pressure, prevent or delay the onset of hypertension, enhance antihypertensive drug efficacy, and decrease cardiovascular risk. In some individuals, a 1600-mg sodium DASH eating plan has blood pressure-lowering effects similar to single drug therapy. A combination of 2 (or more) lifestyle modifications can achieve even better results. For overall cardiovascular risk reduction, patients should be strongly counseled to quit smoking.
|Modification||Recommendation||Approximate SBP Reduction|
|Weight reduction||Maintain normal body weight (BMI 18.5-24.9 mg/kg2)||5-20 mm Hg/10kg|
|Adopt DASH eating plan||Consume a diet rich in fruits, vegetables, and low-fat dairy products, with a reduced content of saturated and total fat||8-14 mm Hg|
|Dietary sodium restriction||Reduce dietary sodium to no more than 100 mmol/d (2.4 g sodium or 6 g sodium chloride)||2-8 mm Hg|
|Physical activity||Engage in regular aerobic physical activity, such as brisk walking (at least 30 min/d, most days of the week)||4-9 mm Hg|
|Moderation of alcohol consumption||Limit consumption to no more than 2 drinks (eg, 24 oz beer, 10 oz wine, or 3 oz 80-proof whiskey) per day in most men, and to no more than 1 drink per day in women and in lighter-weight persons)||2-4 mm Hg|
DASH: Dietary Approaches to Stop Hypertension; SBP: systolic blood pressure.
*For overall cardiovascular risk reduction, stop smoking.
The effects of implementing these modifications are dose- and time-dependent, and could be greater for some individuals.
From Chobanian, Hypertension., 2003.
The DASH diet is efficacious in treating prehypertension in a diverse population. Men and women, regardless of race or age, experienced a significant reduction in blood pressure, which was particularly efficacious in blacks. The blood pressure-lowering effect of DASH in prehypertension was confirmed in the DASH sodium trial and the PREMIER trial.
The DASH sodium trial included a total of 412 randomly chosen participants assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order, with increased consumption of healthier foods. Results of this study revealed that patients who reduced their sodium intake to levels below the current recommendation of 100 mmol/d and followed a diet rich in fruits, vegetables, low-fat diary products, whole grains, fish and nuts lowered their blood pressure substantially, with greater effects in combination than alone. In fact, according to the study results, the combination of the 2 dietary interventions lowered SBP more in participants with hypertension than in those without hypertension (P = .004), and more in women than in men (P = .02).
The level of dietary sodium had approximately twice as great an effect on blood pressure with the control diet as it did with the DASH diet (P < .001), and there was a greater response of blood pressure to progressively lower levels of sodium intake. In the control diet, a reduction in the sodium intake of about 40 mmol/d from the intermediate sodium level lowered blood pressure more than a similar reduction in the sodium intake from the high level (P = .03 for SBP, P = .045 for DBP).
The DASH diet, as compared with the control diet, resulted in a significantly lower SBP at every sodium level and in a significantly lower DBP at the high and intermediate sodium levels. It had a larger effect on both SBP and DBP at high sodium levels than it did at low ones (P < .001). As compared with the high-sodium control diet, the low-sodium DASH diet produced greater reductions in SBP and DBP than either the DASH diet alone or a reduction in sodium alone.
The effects of sodium were greater in participants with hypertension than in those without hypertension (P = .01 on the control diet; P = .003 on the DASH diet), in blacks on the control diet than in participants of other races or ethnic groups on that diet (P = .007), and in women on the DASH diet than in men on that diet (P = .04).
As compared with the combination of the control diet and a high level of sodium, the combination of the DASH diet and a low level of sodium lowered SBP by 11.5 mm Hg in participants with hypertension (12.6 mm Hg for blacks; 9.5 mm Hg for others), by 7.1 mm Hg in participants without hypertension (7.2 mm Hg for blacks; 6.9 mm Hg for others), and by 6.8 mm Hg in men and 10.5 mm Hg in women (P < .001 in all subgroups).
Compared with a typical American control diet, the DASH dietary pattern reduced SBP by 5.5 mm Hg and DBP by 3.0 mm Hg overall (each P < .001). In the participants with prehypertension, corresponding reductions were 3.5 mm Hg (P < .001) and 2.1 mm Hg (P = .003). Overall, prehypertension was reduced to normal blood pressure in 62% of study participants following the DASH dietary pattern.[5,8]
The PREMIER trial further supported the evidence of the DASH trials. The PREMIER trial documented that patients with above-optimal blood pressure, including stage 1 hypertension, can make multiple lifestyle changes that lower blood pressure and control hypertension. The randomized trial included 810 adults (62% women; 34% African American) from enrollment at 4 clinical centers between January 2000-2001. All participants had above-optimal blood pressure, including stage 1 hypertension (120-159 mm Hg SBP and 80-95 mm Hg DBP), but none were taking antihypertensive medications. The study participants were randomized to 1 of 3 intervention groups: 1) established, a behavioral intervention that implemented established recommendations such as weight loss, reduced sodium, increased physical activity, and limited alcohol intake (n = 268); 2) established plus DASH, which also implemented the DASH diet (n = 269); and 3) an advice-only comparison group (n = 273).
At the conclusion of the PREMIER trial, both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Gradients in blood pressure and hypertensive status were noted among all groups. After subtracting change in advice only, the trial reported the mean net reduction in SBP to be 3.7 mm Hg (P < .001) in the established group and 4.3 mm Hg (P < .001) in the established plus DASH group. The SBP difference between the 2 groups was 0.6 mm Hg (P = 0.43).
The smallest reduction in blood pressure occurred in the advice-only group, while the greatest reduction occurred in the established plus DASH group. A total of 77% of participants with stage 1 hypertension at baseline in the established plus DASH group had a SBP of < 140 mm Hg and a DBP of < 90 mm Hg at 6 months (Figure 2).
Figure 2. PREMIER study: mean systolic blood pressure and diastolic blood pressure over time. DASH: Dietary Approaches to Stop Hypertension. From Appel, JAMA., 2003.
Weight loss is also important for the prevention and treatment of hypertension. A meta-analysis of randomized controlled trials published in 2003 by Neter and associates estimated the effect of weight reduction on blood pressure overall and in population subgroups. A total of 25 trials published between 1966 and 2002 with a total of 4874 participants were included. A net weight reduction of 5.1 kg by means of energy restriction, increased physical activity, or both reduced SBP by 4.44 mm Hg and DBP by 3.57 mm Hg. Blood pressure reductions were approximately 1 mm Hg SBP and DBP when expressed per kilogram of weight loss. Significantly larger reductions in blood pressure were observed among populations with an average weight loss > 5 kg than in populations with less weight loss.
Although clinical trials have demonstrated that increased physical activity can lower blood pressure regardless of effect on body weight, this finding is not universal. Two meta-analyses concluded that physical activity independently lowers blood pressure.[9,10] In the study by Whelton and colleagues, the authors examined 54 clinical trials where intervention and control groups only differed in aerobic exercise. The authors found a statistically significant reduction in mean SBP and DPB in the aerobic-exercise group vs the control group of -3.84 mm Hg and -2.58 mm Hg, respectively, P < .001.
Finally, while existing literature is inconsistent on the effect of alcohol intake on elevated blood pressure, overall the evidence favors moderate alcohol intake. The currently recommended limits for the management of prehypertension are 2 ounces per day for men and 1 ounce per day for women.
The DASH diet and weight loss have also been associated with reductions in other risk factors for CVD, including reductions in total cholesterol, LDL-C, and inflammatory mediators such as C-reactive protein. Weight loss has also been associated with reductions in blood sugar and insulin resistance.
Despite the proven benefit of lifestyle modification on lowering blood pressure, more than two thirds of hypertensive patients will require 2 or more antihypertensive agents selected from different drug classes to properly control their hypertension. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 60% of individuals whose blood pressure was controlled to < 140/90 mm Hg received 2 or more agents and only 30% overall were controlled with 1 drug. In hypertensive patients with lower blood pressure goals or with substantially elevated blood pressure, 3 or more antihypertensive drugs may be required.
The Framingham Heart Study is a prospective longitudinal cohort study that began in 1948 by enrolling 5209 individuals between 28 and 62 years of age with no CVD. Vasan and associates conducted a study of individuals within this larger cohort to determine the residual lifetime risk of developing hypertension. Individuals without hypertension in 1975 were selected for this study and were followed from 1976 to 1998. The investigators reported that the overall lifetime risk of developing hypertension was approximately 90% for men and women who were not hypertensive at 55 or 65 years of age and survived to age 80 to 85 (Figure 3).
Figure 3. Residual lifetime risk of hypertension in women and men aged 65 years. Data for 65-year-old men in the 1952 to 1975 period are truncated at 15 years since there were few participants in this age category who were followed beyond this time interval. From Vasan, JAMA., 2002.
Among participants of the Framingham Study with normal blood pressure values (range 120-129/80-84 mm Hg), 17.6% between ages 30 and 64 years and 25.5% 65 years of age and older progressed to hypertension over 4 years. In the group with blood pressure levels in the 130 to 139/85 to 89 mm Hg range, the incidence of hypertension was 37.3% and 49.5% for the 30- to 64-year and 65-year and older groups, respectively.
The Trial of Hypertension (TROPHY) study was conducted to determine if treatment of prehypertension reduces the incidence of hypertension development. Prehypertensive patients were randomized to receive an angiotensin-receptor blocker (ARB) or placebo for 2 years, after which all patients were given placebo. After 2 years, 40% of prehypertensive individuals (mean age 48.5 years) receiving placebo developed hypertension compared to 13.5% receiving ARB therapy. At the end of 4 years, 63% of patients in the placebo group and 53% of patients who were formerly treated with an ARB therapy developed hypertension. Of the estimated 65 million people in the United States with prehypertension, approximately 25 million have blood pressure levels similar to the study participants. Based on these data, the investigators hypothesized that hypertension will develop in nearly 16 million people over the next 4 years.
Because of these rates of progression of prehypertension to hypertension, annual or biannual monitoring of blood pressure in prehypertensive persons would seem appropriate.
The JNC-7 emphasizes that even slightly elevated blood pressure increases cardiovascular risk. Beginning at a blood pressure value of 115/75 mm Hg, the risk of CVD doubles with each increment of 20/10 mm Hg.[1,4]
Prehypertension is associated with an increased incidence of CVD, particularly in those with blood pressure levels in the 130 to 139/85 to 89 mm Hg range, and for those with diabetes or glucose intolerance.[16,17] Vasan and colleagues investigated the relationship between blood pressure and CVD in patients with high-normal blood pressure who participated in the Framingham Heart study. A total of 6859 patients without hypertension were followed for a mean of 11.1 years. Results from the study concluded that high-normal blood pressure (SBP 130 to 139 mm Hg, DBP 85 to 89 mm Hg, or both) is associated with an increased risk of CVD and that risk increases with age. The 10-year cumulative incidence of CVD among study participants aged 35 to 64 years who had high-normal blood pressure was 4% for women and 8% for men. In older subjects (those aged 65 to 90 years), the incidence was 18% for women and 25% for men. As compared with optimal blood pressure, high-normal blood pressure was associated with a risk-factor-adjusted hazard ratio for CVD of 2.5 (95% confidence interval [CI], 1.6-4.1) in women and 1.6 (95% CI, 1.1-2.2) in men.
A longitudinal, population-based, US cohort study conducted by Liszka and associates found that prehypertension was associated with increased risk of major cardiovascular events independent of other cardiovascular risk factors. The study comprised participants of the National Health and Nutrition Examination Survey I (NHANES I), which consisted of approximately 32000 participants aged 1 to 74. Ninety-three percent of prehypertensive individuals had at least 1 cardiovascular risk factor. Low prehypertension (120-129/80-84 mm Hg) was associated with increased CVD in unadjusted analyses (1.56 [95% CI, 1.23-1.98]) but was not statistically significant in adjusted analyses (1.24 [95% CI, 0.96-1.59]). High-normal blood pressure (130-139/85-89 mm Hg) remained a predictor of CVD in unadjusted (2.13 [95%, CI 1.64-2.76]) and adjusted (1.42 [95% CI, 1.09-1.84]) analyses. Overall, prehypertension was associated with increased risk for CVD (1.79 [95% CI 1.40-2.24]) in unadjusted analysis. After adjustment for cardiovascular risk factors, the relationship between prehypertension and CVD was diminished but persisted (1.32 [95% CI 1.05-1.65]) (Figure 4).
Figure 4. Unadjusted cumulative cardiovascular disease event-free survival by blood pressure category. From Liszka, Ann Fam Med., 2005.
Greenlund and coworkers analyzed data for 3488 patients aged 20 years and older from the 1999-2000 NHANES and found that being overweight or obese was the most prevalent risk factor among individuals with prehypertension, with 64% being overweight or obese (Table 3).
|Cholesterol ≥ 200 mg/dL||42.0 (1.76)||1.00 (Referent)||59.1 (2.16)||1.63 (1.24-2.14)||71.0 (1.79)||1.64 (1.19-2.26)|
|Cholesterol ≥ 240 mg/dL||13.4 (1.25)||1.00 (Referent)||19.3 (1.87)||1.33 (0.90-1.96)||23.5 (1.54)||1.31 (0.86-1.99)|
|BMI ≥ 25 kg/m2||53.5 (2.26)||1.00 (Referent)||63.9 (1.94)||1.46 (1.20-1.79)||79.3 (1.63)||3.34 (2.50-4.46)|
|BMI ≥ 30 kg/m2||19.2 (1.77)||1.00 (Referent)||31.6 (1.89)||2.26 (1.67-3.06)||45.3 (2.03)||4.42 (3.17-6.18)|
|Diabetes mellitus||2.4 (0.60)||1.00 (Referent)||4.3 (0.90)||1.22 (0.58-2.58)||13.5 (1.06)||2.47 (1.28-4.74)|
|Current smoker||29.8 (2.45)||1.00 (Referent)||26.6 (1.71)||0.90 (0.71-1.13)||16.7 (1.50)||0.70 (0.52-0.93)|
|>/- Above-optimal risk factor||78.4 (2.16)||1.00 (Referent)||88.8 (1.35)||1.83 (1.30-2.58)||95.2 (0.76)||3.85 (2.49-5.96)|
|≥ 1 Clinically high risk factor||50.9 (2.66)||1.00 (Referent)||64.1 (2.04)||1.65 (1.30-2.09)||76.5 (1.21)||2.82 (2.22-3.58)|
BMI: body mass index; CI: confidence interval; NHANES: National Health and Nutrition Examination Survey; OR: odds ratio.
*Values are from logistic regression models that included hypertension status, age group, sex, and race/ethnicity as covariables.
Cholesterol level of 200 mg/dL or greater, BMI of 25 kg/m2 or greater, diabetes mellitus, and current smoker.
Cholesterol level of 240 mg/dL or greater, BMI of 30 kg/m2 or greater, diabetes mellitus, and current smoker.
From Greenlund, Arch Intern Med., 2004.
The percentage of study participants who were overweight or obese was higher in those with prehypertension than in those with blood pressure in the normal range. The likelihood of being overweight (OR, 1.46; 95% CI, 1.20-1.79) or obese (OR, 2.26; 95% CI, 1.67-3.06) remained significant after adjusting for age, sex, and race/ethnicity. Similar results were observed for participants with hypertension compared with those with normal blood pressure.
The percentage of patients in the study with above-normal and high cholesterol levels was greater in groups with prehypertension and hypertension than in those with normal blood pressure. Individuals with prehypertension were significantly more likely to have elevated cholesterol levels (≥ 200 mg/dL [≥ 5.17 mmol/L]) than were people with optimal blood pressure levels (OR, 1.63; 95% CI, 1.24-2.14); the same was true of individuals with hypertension (OR, 1.64; 95% CI, 1.19-2.26).
As you may recall, our case patient has a waist circumference of 42 inches.
Although obesity is independently associated with higher blood pressure levels,
it is also related to physical inactivity and poor nutrition, reinforcing the
need to reduce the risk of hypertension through
Men are at greater risk for cardiovascular and renal disease than premenopausal women of the same age. After menopause, however, blood pressure increases in women to levels even higher than those seen in men (Figure 5). Hormone replacement therapy in most cases does not significantly reduce blood pressure in postmenopausal women, which suggests that loss of estrogen may be just 1 of several components associated with higher blood pressure in postmenopausal women.
Figure 5. Effect of aging and gender on prevalence of hypertension. From Reckelhoff, Hypertension., 2001.
*Too few individuals available for statistical evaluation
A cross-sectional analysis of national representative data collected from 4805 adults 18 years and older surveyed in the 1999-2000 NHANES found that African American men and women had higher SBP values than the other ethnic groups and that African American women had higher DBP values than women of other ethnic backgrounds.
Hsia and associates conducted a study examining cardiovascular risk in postmenopausal women. The study population came from the Women's Health Initiative and included 161,808 postmenopausal women enrolled at 40 clinical sites in 4 randomized trials and an observational study. The investigators determined the prevalence of prehypertension, its association with other coronary risk factors, and the risk for incident CVD events in 60,785 postmenopausal women during 7.7 years of follow-up. Prehypertension was present at baseline in 39.5%, 32.1%, 42.6%, 38.7%, and 40.3% of white, African American, Hispanic, American Indian, and Asian women, respectively. Age, BMI, and prevalence of diabetes mellitus and hypercholesterolemia increased across blood pressure categories, whereas smoking decreased (all P < .0001).
Compared with normotensive women, adjusted hazard ratios for women with prehypertension were 1.58 (95% CI, 1.12-2.21) for cardiovascular death, 1.76 (95% CI, 1.40-2.22) for myocardial infarction, 1.93 (95% CI, 1.49-2.50) for stroke, 1.36 (95% CI, 1.05-1.77) for hospitalized heart failure, and 1.66 (95% CI, 1.44-1.92) for any cardiovascular event. Hazard ratios for the composite outcome with prehypertension did not differ between ethnic groups (P = .71). Among women with hypertension, 15% were unaware of the condition, whereas 5.5% were aware but untreated.
Based on NHANES data from 1999-2000, investigators found that compared with white and African American hypertensive patients, Mexican Americans were less likely to be aware of their hypertension, to be told to take medication or adopt lifestyle modifications to control hypertension, or to follow the advice once given. These rates were lower in younger patients (18 to 39 years) when compared to older patients. Overweight and obese hypertensive patients had better awareness, management, treatment, and control of hypertension than patients who were not overweight (Table 4).
|Variable||American Adults, % (SE)|
|Awareness (Told Had Hypertension)||Told to Control for Hypertension||Management (Lifestyle Modification or Medication)||Treatment (Take Prescription)||Control (SBP < 140 mm Hg; DBP < 90 mm Hg)|
|All||37.5 (1.2)||34.7 (1.2)||32.5 (1.1)||27.0 (1.0)||14.5 (0.9)|
|Men||31.4 (1.8)||28.9 (1.6)||27.1 (1.5)||21.4 (1.4)||12.8 (1.0)|
|Women||45.0 (1.9)||42.0 (1.9)||39.2 (1.9)||34.0 (1.8)||16.6 (1.5)|
|Non-Hispanic white||38.0 (1.6)||35.0 (1.5)||32.4 (1.4)||27.9 (1.2)||15.7 (1.0)|
|Non-Hispanic black||44.2 (2.3)||42.8 (2.4)||41.0 (2.5)||32.2 (2.0)||14.6 (1.2)|
|Mexican American||26.3 (2.5)||22.9 (2.1)||21.6 (2.1)||14.7 (1.5)||6.5 (1.3)|
|Other||33.3 (3.3)||30.2 (3.2)||29.9 (3.1)||21.7 (2.9)||10.9 (2.2)|
|18-39||16.5 (1.9)||13.5 (1.7)||11.2 (1.4)||5.0 (1.1)||2.5 (0.9)|
|40-59||41.0 (2.1)||37.7 (1.9)||35.4 (1.8)||29.1 (1.8)||19.6 (1.8)|
|≥ 60||54.4 (1.6)||52.3 (1.7)||50.5 (1.7)||46.4 (1.8)||20.6 (1.5)|
|<High school||41.4 (2.3)||38.4 (2.4)||36.4 (2.3)||31.1 (2.0)||13.4 (1.4)|
|High school||40.1 (2.7)||37.6 (2.4)||34.7 (2.1)||28.5 (1.8)||14.5 (1.7)|
|>High school||33.6 (1.6)||30.7 (1.4)||38.9 (1.4)||23.7 (1.4)||15.2 (1.4)|
|Body weight status**|
|BMI < 25||21.3 (1.8)||20.0 (1.7)||17.9 (1.4)||15.5 (1.2)||8.0 (1.2)|
|BMI ≥ 25 but < 30||38.2 (1.8)||34.9 (1.9)||33.3 (1.8)||27.9 (1.7)||15.7 (1.6)|
|BMI > 30||49.4 (2.1)||46.1 (2.1)||43.7 (1.9)||35.3 (1.8)||18.4 (1.5)|
NHANES: National Health and Nutrition Examination Study; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure.
*Men are the reference group.
The difference is statistically significant (P < .05).
Non-Hispanic white is the reference group.
§Age 40 to 59 years is the reference group.
¶More than high school education is the reference group.
**BMI greater than 25 is the reference group.
From Wang, Arch Intern Med., 2004.
The higher prevalence of hypertension in African Americans at younger ages than in whites and Mexican Americans suggests the need for more aggressive efforts at prevention and control in this group. Clinicians need to remain aware that persons with above-normal blood pressure values are more likely to have other CVD risk factors.
The TROPHY study, the first to study drug treatment of prehypertension, reported that treatment of prehypertension with candesartan reduced the risk of incident hypertension during the study period of 4 years. In fact, stage 1 hypertension developed in nearly two thirds of untreated patients with prehypertension. Participants were eligible for enrollment if they were not being treated for hypertension, if their blood pressure was lower than 160/100 mm Hg at the first clinic visit, and if the average of 3 blood pressure measurements at 3 visits was SBP 130 to 139 mm Hg and DBP 89 mm Hg or lower, or SBP of 139 mm Hg or lower and DBP 85 to 89 mm Hg. A total of 409 participants were randomly assigned to candesartan, and 400 to placebo. Data on 772 participants (391 in the candesartan group and 381 in the placebo group; mean age, 48.5 years; 59.6% men) were available for analysis. During the first 2 years, hypertension developed in 154 participants in the placebo group and 53 of those in the candesartan group (relative risk reduction, 66.3%; P < .001). After the first 2 years of the study, the candesartan group was switched to placebo. After 4 years, hypertension developed in 240 participants in the placebo group and 208 of those in the candesartan group (relative risk reduction, 15.6%; P < .007). Serious adverse events occurred in 3.5% of the participants assigned to candesartan and 5.9% of those receiving placebo.
Lifestyle modification is the cornerstone of management in all patients with prehypertension or with the metabolic syndrome, but if blood pressure exceeds 140/90 mm Hg, pharmacological therapy is indicated as described in the hypertension treatment algorithm from the JNC-7 (Figure 6).
Figure 6. Algorithm for treatment of hypertension. From Chobanian, Hypertension., 2003.
According to the JNC-7, most hypertensive patients will require 2 or more antihypertensive medications to achieve their blood pressure goals. The addition of a second drug from a different class should be considered when use of a single agent in adequate doses fails to achieve the goal. Two drugs should be considered -- either as separate prescriptions or in fixed-dose combinations -- when the patient's blood pressure is more than 20 mm Hg above the systolic goal or 10 mm Hg higher than the diastolic goal.
Using more than 1 drug to treat hypertension increases the likelihood that a patient will achieve their blood pressure goal faster than with monotherapy. The use of multidrug combinations often produces greater blood pressure reduction at lower doses of the component agents, which leads to fewer side effects. The use of fixed-dose combinations may be more convenient and may simplify the treatment regimen; it is possible they may also cost less than the individual components prescribed separately.
Generic drugs should be considered to further reduce prescription costs. The JNC-7 also suggests that separate prescriptions of multiple drugs available generically may cost less than non-generic, fixed-dose combinations. The starting dose of most fixed-dose combinations is usually lower than the doses used in clinical trials. Therefore, the committee suggests that the doses of these agents be titrated upward to achieve the blood pressure goal before adding other drugs.
If blood pressure goal is not achieved through lifestyle modification, JNC-7 recommends thiazide-type diuretics as initial therapy for most patients, either alone or in combination with one of the other classes (eg, ACE inhibitors, ARBs, beta-blockers, calcium channel blockers). These drugs have also been shown to reduce 1 or more hypertensive complications in randomized controlled trials. Selection of 1 of these other agents as initial therapy is recommended when a diuretic cannot be used or when a compelling indication is present. Recent data would suggest that beta blockers are not a good first-line option in the primary prevention of hypertension. A meta-analysis showed that beta blocker therapy is inferior to other therapies in stroke prevention when administered as a first-line agent. The authors of this meta-analysis included 7 randomized controlled trials of over 27000 patients and found that the relative risk for stroke was 16% higher for beta blockers than for other drugs. Based on these data, the National Institute for Health and Clinical Excellence (NICE) in the UK has recommended beta blockers as fourth line antihypertensive therapy.
Since the first VA Cooperative trial published in 1967, thiazide-type diuretics have been the basis of antihypertensive therapy in most placebo-controlled trials in which CVD events -- including strokes, coronary heart disease, and heart failure -- have been reduced by lowering blood pressure. Clinical trial data also demonstrate that lowering blood pressure with other classes of drugs can also reduce the complications of hypertension. However, in trials comparing diuretics with other classes of antihypertensive agents, diuretics have been effective in preventing the cardiovascular complications of hypertension.
Data from the ALLHAT study, which involved more than 33,000 people with
hypertension and at least 1 other cardiac risk factor, reported no differences
in the primary coronary heart disease outcome or mortality between participants
treated with the thiazide-type diuretic chlorthalidone, the ACE inhibitor
lisinopril, or the calcium channel blocker amlodipine. Stroke incidence was
greater with lisinopril than chlorthalidone therapy, but these differences were
present primarily in African Americans who also had less blood pressure lowering
with lisinopril than diuretics. The incidence of heart failure was greater in
African American and white individuals receiving amlodipine and lisinopril as
compared with those receiving chlorthalidone.[1,22] The ALLHAT study
did, however, demonstrate an increased risk of new-onset diabetes in the
thiazide diuretic arm. At year 2, the odds ratio of developing diabetes was
lower in the lisinopril group (0.55, 0.43-0.70) and the amlodipine group (0.73,
0.58-0.91) versus the diuretic group, P < .001 and P <
More than two thirds of hypertensive individuals cannot be controlled on 1 drug and will require 2 or more antihypertensive agents selected from different drug classes. In ALLHAT, 60% of those whose blood pressure was controlled to < 140/90 mm Hg received 2 or more agents, and only 30% overall were controlled on 1 drug.[1,22]
The JNC-7 highlights "compelling indications" when the use of individual drug classes should be considered. These indications include heart failure, postmyocardial infarction, high coronary disease risk, diabetes, chronic kidney disease, and recurrent stroke prevention. As shown in Table 5 below, the JNC-7 recommends the use of ACE inhibitors for all six compelling indications based on extensive clinical trial data. In patients who are intolerant to ACE inhibitors, ARBs may be utilized.
|Compelling Indication||Recommended Drugs||Clinical Trial Basis|
|Heart failure||XX||XX||XX||XX||XX||ACC/AHA Heart Failure Guideline, MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, ValHEFT, RALES, CHARM|
|Postmyocardial infarction||XX||XX||XX||ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS|
|High coronary disease risk||XX||XX||XX||XX||ALLHAT, HOPE, ANBP2, LIFE, CONVINCE, EUROPA, INVEST|
|Diabetes||XX||XX||XX||XX||XX||NKF-ADA Guideline, UKPDS, ALLHAT|
|Chronic kidney disease||XX||XX||NKF-ADA Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK|
|Recurrent stroke prevention||XX||XX||PROGRESS|
From Chobanian, 2003.
Recent data suggests that ACE inhibitors and ARBs have a similar blood-pressure dependent effect on major cardiovascular events. The Blood Pressure Lowering Treatment Trialists' Collaboration Group (BPLTT) conducted meta-regression analyses to evaluate the blood-pressure dependent and independent effects of ACE inhibitors and angiotensin receptor blockers on major cardiovascular events. Using 26 trials, the authors compared the relative risk for stroke, coronary heart disease, and heart failure. The analyses showed that ACE inhibitors and ARBs had comparable blood-pressure dependent reductions in risk for all three outcomes. ACE inhibitors showed a blood-pressure independent reduction in the risk of CHD of 9% (P = 0.002). However, neither showed evidence for blood-pressure independent effects for stroke or heart failure.
Elijah Saunders, MD, FACC, FACP
Professor of Medicine, Cardiology; Head, Section of Hypertension, University of Maryland School of Medicine, Baltimore, Maryland
Disclosure: Elijah Saunders, MD, has disclosed that he has received grants for clinical research, educational activities, and served as an advisor or consultant for Abbott, Pfizer, Novartis, and GlaxoSmithKline. Dr. Saunders has also disclosed that he owns stock, stock options, or bonds in Pfizer.