Achieving blood pressure goals globally: five core actions for health-care professionals. A worldwide call to action.

The prevalence of hypertension continues to rise across the world, and most patients who receive medical intervention are not adequately treated to goal. A Working Group including representatives of nine international health-care organizations was convened to review the barriers to more effective blood pressure control and propose actions to address them. The group concluded that tackling the global challenge of hypertension will require partnerships among multiple constituencies, including patients, health-care professionals, industry, media, health-care educators, health planners and governments. Additionally, health-care professionals will need to act locally with renewed impetus to improve blood pressure goal rates. The Working Group identified five core actions, which should be rigorously implemented by practitioners and targeted by health systems throughout the world: (1) detect and prevent high blood pressure; (2) assess total cardiovascular risk; (3) form an active partnership with the patient; (4) treat hypertension to goal and (5) create a supportive environment. These actions should be pursued with vigour in accordance with current clinical guidelines, with the details of implementation adapted to the economic and cultural setting.

Development of explicit criteria to measure adherence to hypertension guidelines.

Measures of adherence to hypertension guidelines have historically been based on prescription data or physician survey data regarding treatment practices. These methods have limitations that decrease their accuracy. As part of a randomized controlled study testing the effects of pharmacist/physician collaboration on adherence to hypertension guidelines, the investigators and an expert panel developed a JNC 7 measurement tool. The final guideline adherence measurement tool includes 22 explicit criteria in four domains of care. An exploratory factor analysis, conducted to assess the structure of the tool, suggests three underlying treatment dimensions in hypertension care. The adherence measurement tool will allow researchers to link specific elements of care to improved blood pressure control. In addition, use of the tool will provide clinicians with a taxonomy for evaluating practice and describing the effect of improved patient care on patient outcomes.

The paradigm has shifted to systolic blood pressure.

Since the middle of the 20th century, most physicians and epidemiologists assessed the risks associated with hypertension based on the level of diastolic blood pressure (DBP). In a classic paper in 1971, the Framingham Heart Study clearly showed that systolic BP more accurately described the risk of all the complications we attribute to hypertension. It took 22 years until JNC V in 1993 also used systolic blood pressure (SBP) to define hypertension in US national guidelines. Since then, the paradigm has shifted dramatically. In JNC VI (1997) and JNC VII (2003), SBP has become the primary focus of risk stratification and treatment goals. This shift is a result of the Framingham results being confirmed by many others analyses, the most compelling of which is the recently published report of the Prospective Collaborative Study Group, which pooled 61 observational studies in more than 1 million volunteers with a collective experience of more than 12 million person-years. This group showed that the SBP level at baseline was a significantly more informative reading than DBP for predicting strokes and coronary heart disease (CHD). Furthermore, three trials of older individuals with isolated systolic hypertension, SHEP, SYST-Eur, and SYST-China, unambiguously demonstrated that effective antihypertensive therapy lowered the rate of strokes, heart failure, CHD, and even all-cause mortality. Finally, the World Health Organization (WHO)/International Society of Hypertension (ISH) Hypertension Trialists also showed that the level of SBP achieved in clinical trials comparing different antihypertensives with placebo and with each other was the strongest determinant of how effectively strokes and CHD events were reduced, although a similar relationship was not evident for heart failure. A recent metaregression analysis using new trials, many of which were used by the Trialists, and older studies not included in their analysis also showed that small differences in SBP can have a dramatic impact on cardiovascular outcomes. If there is one thing we have learned in the recent past, it is the need for us to focus on lowering SBP and getting it down to a reasonable goal. We have also learned that to do so, we will need to combine a variety of lifestyle and pharmacological approaches, always with combinations of drugs that will usually contain a low-dose thiazide-type diuretic with other antihypertensives.

Safety of controlled-onset extended-release verapamil in middle-aged and older patients with hypertension and coronary artery disease.

BACKGROUND: Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients. METHODS: Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (>/=65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test. RESULTS: In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration of COER verapamil in any subgroup. CONCLUSION: These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.

One-year study of felodipine or placebo for stage 1 isolated systolic hypertension.

Asubstantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure <90 mm Hg), but there are currently no data showing that drug treatment is effective, safe, and/or beneficial. To compare the effects of active treatment compared with placebo on blood pressure, left ventricular hypertrophy, and quality of life among older stage 1 isolated systolic hypertensive patients, a randomized, double-blind, parallel-group, multicenter clinical trial comparing felodipine (2.5, 5, or 10 mg once daily) and matching placebo was performed in 171 patients (49% male, average age 66+/-7 years, with 49% white and 30% Hispanic) with a baseline blood pressure of 149+/-7/83+/-6 mm Hg. During 52 weeks of treatment, patients randomized to active treatment achieved significantly lower blood pressures (137.0+/-11.7/80.2+/-7.6 mm Hg for extended-release felodipine versus 147.5+/-16.0/83.5+/-9.7 mm Hg for placebo, P<0.01 for each), a reduced incidence of left ventricular hypertrophy (7% for extended release felodipine versus 24% for placebo, P<0.04), and improved quality of life (change in Psychological General Well-Being index, 3.0+/-6.8 for extended-release felodipine versus -0.8+/-10.3 for placebo, P<0.01) versus baseline. There were no clinically significant differences between treatments in tolerability or adverse effects. Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically. Treatment reduced progression to the higher stages of hypertension, reduced the incidence of left ventricular hypertrophy, and improved an overall measure of the quality of life. Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension.

Pulse pressure and risk of cardiovascular events in the systolic hypertension in the elderly program.

Pulse pressure has been related to higher risk of cardiovascular events in older persons. Isolated systolic hypertension is common among the elderly and is accompanied by elevated pulse pressure. Treatment of isolated systolic hypertension may further increase pulse pressure if diastolic pressure is lowered to a greater extent than systolic pressure. Little is known regarding pulse pressure as a predictor of cardiovascular outcomes in elderly persons with isolated systolic hypertension, and the influence of treatment on the pulse pressure effect. We assessed the relation between pulse pressure, measured throughout the follow-up period, and the incidence of coronary heart disease (CHD), heart failure (HF), and stroke in 4,632 participants in the Systolic Hypertension in the Elderly Program, a 5-year randomized, placebo-controlled clinical trial of treatment of isolated systolic hypertension in older adults. In the treatment group, a 10-mm Hg increase in pulse pressure was associated with a statistically significant 32% increase in risk of HF and a 24% increase in risk of stroke after controlling for systolic blood pressure and other known risk factors, as well as with a 23% increase in risk of HF and a 19% increase in risk of stroke after controlling for diastolic blood pressure and other risk factors. Pulse pressure was not significantly associated with HF or stroke in the placebo group, nor with incidence of CHD in either the placebo or treatment group. These results suggest that pulse pressure is a useful marker of risk for HF and stroke among older adults being treated for isolated systolic hypertension.

Chronotherapeutic delivery of verapamil in obese versus non-obese patients with essential hypertension.

BACKGROUND: The effect of controlled-onset, extended-release (COER) verapamil on haemodynamic parameters in obese and non-obese patients is evaluated in this analysis. METHODS: Data were pooled from three clinical trials evaluating efficacy and tolerability of COER-verapamil. Hypertensive men and women (stage I to III) were randomised to COER-verapamil (180-540 mg at bedtime) or placebo for 4-8 weeks and stratified according to body mass index (BMI-obese > 28 kg/m2). Efficacy was assessed as change from baseline in blood pressure (BP), heart rate, and rate-pressure product during four time periods throughout the dosing interval. Safety and tolerability were assessed by monitoring all adverse events and changes in metabolic laboratory parameters. RESULTS: Reductions in all haemodynamic parameters were significantly greater following COER-verapamil compared with placebo for all time periods. The haemodynamic effects of COER-verapamil in obese (n = 166, BMI = 32.8 kg/m2) and non-obese patients (n = 115, BMI = 25.0 kg/m2) were similar. COER-verapamil was well tolerated in both subgroups, but the incidence of constipation was significantly less in obese patients (P < 0.001). CONCLUSIONS: COER-verapamil is effective in reducing BP, heart rate, and rate-pressure product independently of BMI.

Gender and age effects on the ambulatory blood pressure and heart rate responses to antihypertensive therapy.

BACKGROUND: The aim of this study was to assess potential differences in the 24-h antihypertensive response to treatment with the controlled-onset, extended-release (COER) calcium antagonist, verapamil in men versus women and older versus younger patients with hypertension. METHODS: Meta-analyses were performed of three prospective randomized, double-blind, placebo-controlled trials with COER-verapamil in patients with mid-stage I to stage III essential hypertension. The trials were conducted at medical clinics in the US and Canada in patients with a mean office diastolic blood pressure (BP) of 95 to 115 mm Hg on 2 consecutive weeks and a mean daytime diastolic BP >90 mm Hg. Patients were randomized to treatment with 180 to 540 mg/day of COER-verapamil (N = 273) or placebo (N = 125). Changes from baseline in ambulatory BP and heart rate after COER-verapamil were compared in men versus women and in older versus younger patients. RESULTS: Treatment with COER-verapamil caused significant reductions in 24-h and early-morning systolic and diastolic BP in all of the subpopulations as compared with placebo (P < .001). COER-verapamil induced a greater reduction in both 24-h systolic (-15.1 v -10.0 mm Hg; P < .001) and diastolic (-10.4 v -8.2 mm Hg; P = .003) BP in women compared with men. Older patients showed a greater mean reduction in 24-h diastolic BP (-10.2 v -8.2 mm Hg; P < .05) and heart rate (-5.7 v -4.4 beats/min; P < .05) compared with younger patients. Side effects were similar in all of the COER-verapamil treatment groups. CONCLUSIONS: Both gender and age were significant determinants of the response to COER-verapamil. The antihypertensive effect of verapamil is greater in women than in men and in older patients compared with younger patients.

Hypertension and its treatment in postmenopausal women: baseline data from the Women's Health Initiative.

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%, beta-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.

Cost-effectiveness of the lower treatment goal (of JNC VI) for diabetic hypertensive patients. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

BACKGROUND: The recommendation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) to lower blood pressure (BP) in diabetic patients to less than 130/85 mm Hg may have negative economic consequences. A formal cost-effectiveness analysis was therefore performed, comparing the costs and potential benefits of a BP goal of less than 140/90 mm Hg (as recommended by JNC V) vs less than 130/85 mm Hg (as inJNC VI). METHODS: A 24-cell computer model was populated with costs (1996 dollars), relative risks, and age-specific base-line rates for death and 4 nonfatal adverse events (stroke, myocardial infarction, heart failure, and end-stage renal disease), derived from published data. Costs and benefits were discounted at 3%. RESULTS: For 60-year-old diabetic persons with hypertension, treating to the lower BP goal increases life expectancy by 0.48 (discounted) years and lowers (discounted) lifetime medical costs by $1450 compared with treating BP to less than 140/90 mm Hg. The lower treatment BP goal results in an overall cost savings over a wide range of initial conditions, and for nearly all analyses for patients older than 60 years. CONCLUSIONS: Any incremental treatment for 60-year-olds that costs less than $414 annually and successfully lowers BP from below 140/90 to below 130/85 mm Hg would be cost saving in the long term, due to the reduction in attendant costs of future morbidity. The lower treatment goal recommended for high-risk hypertensive patients compares favorably in cost-effectiveness with many other frequently recommended treatment strategies, and saves money overall for patients aged 60 years and older.

The addition of doxazosin to the therapeutic regimen of hypertensive patients inadequately controlled with other antihypertensive medications: a randomized, placebo-controlled study.

This randomized, double-blind, placebo-controlled study evaluated the use of doxazosin as an add-on therapy for inadequately controlled hypertension. Patients with a sitting diastolic blood pressure (BP) of 95 to 115 mm Hg received either doxazosin (n = 38) or placebo (n = 32) in addition to one or two baseline antihypertensive medications. After an upward titration period, patients were maintained on a fixed dosage of doxazosin (1 to 16 mg/day) or matching placebo for 4 weeks. Doxazosin add-on therapy led to improvements, compared with placebo, in sitting systolic BP (adjusted mean change = -20.9 v -8.5 mm Hg, P = .001), sitting diastolic BP (-13.0 v -8.1 mm Hg, P = .026), and standing systolic BP (-22.0 v -11.5 mm Hg, P = .011). Baseline antihypertensive therapy was gradually tapered or discontinued in patients who achieved a target reduction in BP (sitting diastolic BP of < 90 mm Hg in addition to a minimum improvement of 10 mm Hg in sitting diastolic BP over baseline) with add-on therapy (55% [n = 21] with doxazosin, 31% [n = 10] with placebo). Twelve patients in the doxazosin group maintained the target reduction in BP after complete withdrawal of their baseline antihypertensive therapy, compared with none in the placebo group. A small but statistically significant positive effect on the lipid profile was seen in the doxazosin group during add-on therapy. Doxazosin treatment was well tolerated, with an adverse event profile similar to that of placebo. These findings demonstrate that doxazosin add-on therapy is an effective, well-tolerated treatment strategy for patients with inadequately controlled hypertension.

Implications of a health lifestyle and medication analysis for improving hypertension control.

BACKGROUND: National Health and Nutritional Examination surveys have documented poor rates of hypertension treatment and control, leading to preventable morbidity and mortality. OBJECTIVES: To examine covariation in the medication and health lifestyle beliefs and behaviors of persons with hypertension to identify and profile distinct subgroups of patients. METHODS: A sample of 727 patients with hypertension, weighted to match the 1992 National Health Interview Survey age and sex distribution of patients with hypertension, was interviewed by telephone about their beliefs and behaviors regarding hypertension and its management. Cluster analysis of key variables was used to identify 4 patient types. RESULTS: Subgroups differed significantly. Group A members use an effective mix of medication and health lifestyle regimens to control blood pressure. Group B members are most likely to depend on medication and have high adherence rates. Yet they also have high rates of smoking (29%) and alcohol use (average, 104 times per year) and are less likely to exercise regularly. Group C members are most likely to forget to take medication, are likely to be obese, and find it most difficult to comply with lifestyle changes (except for very low rates of smoking and alcohol use). Group D members are least likely to take medication, most likely to change or stop medication without consulting their physician (20%), most likely to smoke (40%), and least likely to control diet (29%). Group A and B members have better health outcomes than group C and D members. CONCLUSIONS: Optimal management strategies are likely to differ for the 4 patient types. Further research should be conducted to validate these findings on a separate sample and to devise and test tailored management algorithms for hypertension compliance and control.

Relation of low body mass to death and stroke in the systolic hypertension in the elderly program. The SHEP Cooperative Research Group.

BACKGROUND: There are scant data on the effect of body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) on cardiovascular events and death in older patients with hypertension. OBJECTIVE: To determine if low body mass in older patients with hypertension confers an increased risk of death or stroke. PATIENTS: Participants were 3975 men and women (mean age, 71 years) enrolled in 17 US centers in the Systolic Hypertension in the Elderly Program trial, a randomized, double-blind, placebo-controlled clinical trial of lowdose antihypertensive therapy, with follow-up for 5 years. MAIN OUTCOME MEASURES: Five-year adjusted mortality and stroke rates from Cox proportional hazards analyses. RESULTS: There was no statistically significant relation of death or stroke with BMI in the placebo group (P = .47), and there was a U- or J-shaped relation in the treatment group. The J-shaped relation of death with BMI in the treated group (P = .03) showed that the lowest probability of death for men was associated with a BMI of 26.0 and for women with a BMI of 29.6; the curve was quite flat for women across a wide range of BMIs. For stroke, men and women did not differ, and the BMI nadir for both sexes combined was 29, with risk increasing steeply at BMIs below 24. Those in active treatment, however, had lower death and stroke rates compared with those taking placebo. CONCLUSIONS: Among older patients with hypertension, a wide range of BMIs was associated with a similar risk of death and stroke; a low BMI was associated with increased risk. Lean, older patients with hypertension in treatment should be monitored carefully for additional risk factors.

Optimal blood pressure: how low should we go?

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines hypertension as systolic blood pressure > or =140 mm Hg or diastolic blood pressure (DBP) > or =90 mm Hg. Evidence shows that even slightly elevated blood pressure significantly increases the risk of morbidity and mortality and only aggressive efforts to reduce blood pressure can significantly reduce this risk. In the recently completed Hypertension Optimal Treatment trial, patients were assigned to one of three target blood pressure groups, reflecting DBP goals of < or =90, < or =85, and < or =80 mm Hg. Aggressive antihypertensive treatment allowed more than 90% of patients to achieve goal DBP of < or =90 mm Hg. This study clearly showed that these defined goals could be safely met and even exceeded. Too few patients with hypertension receive the level of effective treatment achieved in clinical trials. Individuals with poorly controlled blood pressure are at significant risk for cardiovascular and cerebrovascular morbidity and mortality and represent a potentially substantial burden to the healthcare system. Setting appropriate blood pressure goals and working to meet them through aggressive antihypertensive treatment, with multiple agents if necessary, can reduce those risks.

Effects of the chronotherapeutic delivery of verapamil on circadian blood pressure in African-American patients with hypertension.

OBJECTIVE: To evaluate the effects of COER-verapamil on circadian blood pressure (BP) and heart rate in African-American patients with hypertension. DESIGN: Retrospective pooled analyses of efficacy and tolerability data from three prospective, randomized, double-blind, placebo-controlled trials with COER-verapamil in hypertension. PATIENTS/PARTICIPANTS: Sixty-eight African-American patients with stages I-III hypertension (seated diastolic BP, 95-114 mm Hg) were randomized to receive placebo or treatment with 180-540 mg of COER-verapamil once daily at bedtime for 4 to 8 weeks. METHODS: Using ambulatory monitoring, efficacy was assessed by measuring change from baseline in systolic and diastolic BP, heart rate, and the heart rate-systolic pressure product during three time intervals: early morning (0600 to 1000), daytime (0800 to 2200), and nighttime (2200 to 0800). Changes also were compared to data from the non-African-American population. Adverse effects were tabulated at each visit. RESULTS: Mean changes from baseline in early-morning BP, heart rate, and rate-pressure product for patients treated with COER-verapamil were -13.8/-11.2 mm Hg, -6.2 beats/minute, and -1960 mm Hg-beats/min, respectively (P<0.01 for all parameters compared to placebo). Significant and similar reductions also were observed for daytime and nighttime BP, heart rate, and the rate-pressure product. The incidence of side effects in the COER-verapamil-treated patients was similar to placebo and the African-American patients had similar incidences to the non-African-American patients. CONCLUSIONS: The chronotherapeutic delivery of verapamil significantly reduced circadian BP, heart rate, and the rate-pressure product. The side effect profile of COER-verapamil was similar to that of placebo. Thus, this therapy for delivery of a heart-rate lowering calcium channel blocker is a useful antihypertensive strategy for African-American patients with hypertension.

Hypertension in the elderly.

The decade of the 1990s has clarified the perspective on treating hypertension in the elderly and provided a wealth of evidence to assist in the treatment of elevated blood pressure in older persons. Despite this wealth of information, important questions remain about treatment of hypertension in the elderly.