The prevalence of treatment resistant hypertension (TRH) defined as blood pressure (BP) uncontrolled on ≥3 antihypertensive medications in optimal doses, preferably including a diuretic, or controlled on ≥4 BP medications is unknown. Clinical trials suggest that 20–30% of hypertensives have TRH. Using U.S. NHANES data, the prevalence of apparent (a) TRH among treated, uncontrolled (BP ≥140/≥90mmHg) individuals rose from 15.9% in 1988–1994 to 28.0% in 2005–2008; ‘aTRH’ is used, since medication dose, adherence, and measurement artefacts are unavailable in NHANES. About 30–50% of patients with aTRH have pseudoresistance, i.e., inaccurate BP, non-representative BP (‘office’ effect), or non-adherence. The Spanish Ambulatory BP Monitoring Registry reported that 3 in 8 patients with aTRH have ‘office’ resistance with normal ambulatory BP.

The mechanism underlying blood pressure (BP) reduction in the high fruits and vegetables arm of the Dietary Approaches to Stop Hypertension (DASH) study is unknown but may include potassium, magnesium and fibre. This study was designed to separate minerals and fibre from other components of DASH on BP in abdominally obese individuals with metabolic syndrome with pre-hypertension to stage 1 hypertension (obese hypertensives). A total of 15 obese hypertensives and 15 lean normotensives were studied on a standardized usual diet, randomized to DASH or usual diet supplemented with potassium, magnesium and fibre to match DASH, then crossed over to the complementary diet. All diets were 3 weeks long, isocaloric and matched for sodium and calcium. In obese hypertensives, BP was lower after 3 weeks on DASH than usual diet (−7.6±1.4/−5.3±1.4 mm Hg, P<0.001/0.02) and usual diet supplemented (−6.2±1.4/−3.7±1.4 P<0.005/0.06), whereas BP was not significantly different on usual and supplemented diets. BP values were not different among the three diets in lean normotensives. Small artery elasticity was lower in obese hypertensives than in lean normotensives on the usual and supplemented diets (P<0.02). This index of endothelial function improved in obese hypertensives (P<0.02) but not lean normotensives on DASH, and was no longer different from values in lean normotensives (P>0.50). DASH is more effective than potassium, magnesium and fibre supplements for lowering BP in obese hypertensives, which suggest that high fruits and vegetables DASH lowers BP and improves endothelial function in this group by nutritional factors in addition to potassium, magnesium and fibre.

Salt induces oxidative stress in salt-sensitive (SS) animals and man. It is not known whether in SS subjects the low-sodium dietary approaches to stop hypertension (LS-DASH) reduces oxidative stress more than DASH, which is high in antioxidants. To assess the effects of DASH and LS-DASH on oxidative stress, 19 volunteers were studied after 3 weeks of a standardized usual low fruits and vegetables diet (ULFV), followed by 3 weeks on DASH (both diets ∼120 mmol Na+ per day), then 3 weeks on LS-DASH (60 mmol Na+ per day). SS was defined as systolic blood pressure ⩾5 mm Hg lower on LS-DASH than DASH. In SS subjects (N=9), systolic blood pressure was lower on LS-DASH (111.0±2.0 mm Hg) than DASH (118.0±2.2, P<0.01) and ULFV (122.3±2.7, P=0.002). In salt-resistant (SR) volunteers (N=10), systolic blood pressure was lower on DASH (113.0±1.6) than ULFV (119.0±1.8, P<0.05) but not LS-DASH (115.7±1.8). Urine F2-isoprostanes, a marker of oxidative stress, were lower in SS subjects on LS-DASH (1.69±0.24) than ULFV (3.09±0.50, P<0.05) and marginally lower than DASH (2.46±0.44, P<0.20). F2-isoprostanes were not different among the three diets in SR volunteers (2.18±0.29, 2.06±0.29, 2.27±0.53, respectively). Aortic augmentation index, a measure of vascular stiffness, was lower in SS subjects on LS-DASH than either DASH or ULFV, and lower on DASH than ULFV in SR volunteers. In SS but not SR subjects, LS-DASH is associated with lower values for F2-isoprostanes and the aortic augmentation index. The results suggest that LS-DASH decreases oxidative stress, improves vascular function and lowers blood pressure in SS but not SR volunteers.

BACKGROUNDUndefined pathophysiologic mechanisms likely contribute to unsuccessful anti hypertensive drug therapy. The renin test-guided therapeutic (RTGT) algorithm is based on the concept that, irrespective of current drug treatments, subnormal plasma renin activity (PRA) (<0.65 ng/ml/h) indicates sodium-volume excess "V" hypertension, whereas values >= 0.65 indicate renin-angiotensin vasoconstriction excess "R" hypertension.METHODSThe RTGT algorithm was applied to treated, uncontrolled hypertensives and compared to clinical hypertension specialists' care (CHSC) without access to PRA. RTGT protocol: "V" patients received natriuretic anti-"V"drugs (diuretics, spironolactone, calcium antagonists, or alpha(1)-blockers) while withdrawing antirenin "R" drugs (converting enzyme inhibitors, angiotensin receptor antagonists, or beta-blockers). Converse strategies were applied to "R" patients. Eighty-four ambulatory hypertensives were randomized and 77 qualified for the intention-to-treat analysis including 38 in RTGT (63.9 +/- 1.8 years; baseline blood pressure (BP) 157.0 +/- 2.6/87.1 +/- 2.0 mm Hg; PRA 5.8 +/- 1.6; 3.1 +/- 0.3 antihypertensive drugs) and 39 in CHSC (58.0 +/- 2.0 years; BD 153.6 +/- 2.3/91.9 +/- 2.0; PRA 4.6 +/- 1.1; 2.7 +/- 0.2 drugs).RESULTSBP was controlled in 28/38 (74% (RTGT)) vs. 23/39 (59% (CHSC)), P=0.17, falling to 127.9 +/- 2.3/73.1 +/- 1.8 vs. 134.0 +/- 2.8/79.8 +/- 1.9 mm Hg, respectively. Systolic BP (SBP) fell more with RTGT (-29.1 +/- 3.2 vs. -19.2 +/- 3.2 mm Hg, P=0.03), whereas diastolic BP (DBP) declined similarly (P=0.32). Although final anti hypertensive drug numbers were similar (3.1 +/- 0.2 (RTGT) vs. 3.0 +/- 0.3 (CHSC), P=0.73) in "V" patients, 60% (RTGT) vs. 11% (CHSC) of "R" drugs were withdrawn and BP medications were reduced (-0.5 +/- 03 vs. +0.7 +/- 0.3, P=0.01).CONCLUSIONSIn treated but uncontrolled hypertension, RTGT improves control and lowers BP equally well or better than CHSC, indicating that RTGT provides a reasonable strategy for correcting treated but uncontrolled hypertension.

BACKGROUND:Prehypertension is considered a precursor of stage 1 hypertension and a predictor of excessive cardiovascular risk. We investigated whether pharmacologic treatment of prehypertension prevents or postpones stage 1 hypertension.METHODS:Participants with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg, were randomly assigned to receive two years of candesartan (Atacand, AstraZeneca) or placebo, followed by two years of placebo for all. When a participant reached the study end point of stage 1 hypertension, treatment with antihypertensive agents was initiated. Both the candesartan group and the placebo group were instructed to make changes in lifestyle to reduce blood pressure throughout the trial.RESULTS: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 percent men) were available for analysis. During the first two years, hypertension developed in 154 participants in the placebo group and 53 of those in the candesartan group (relative risk reduction, 66.3 percent; P<0.001). After four years, hypertension had developed in 240 participants in the placebo group and 208 of those in the candesartan group (relative risk reduction, 15.6 percent; P<0.007). Serious adverse events occurred in 3.5 percent of the participants assigned to candesartan and 5.9 percent of those receiving placebo.CONCLUSIONS:Over a period of four years, stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension (the placebo group). Treatment of prehypertension with candesartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period. Thus, treatment of prehypertension appears to be feasible. (ClinicalTrials.gov number, NCT00227318.).

Therapeutic inertia (TI), defined as the providers' failure to increase therapy when treatment goals are unmet, contributes to the high prevalence of uncontrolled hypertension (> or =140/90 mm Hg), but the quantitative impact is unknown. To address this gap, a retrospective cohort study was conducted on 7253 hypertensives that had > or =4 visits and > or =1 elevated blood pressure (BP) in 2003. A 1-year TI score was calculated for each patient as the difference between expected and observed medication change rates with higher scores reflecting greater TI. Antihypertensive therapy was increased on 13.1% of visits with uncontrolled BP. Systolic BP decreased in patients in the lowest quintile of the TI score but increased in those in the highest quintile (-6.8+/-0.5 versus +1.8+/-0.6 mm Hg; P<0.001). Individuals in the lowest TI quintile were &33 times more likely to have their BP controlled at the last visit than those in highest quintile (odds ratio, 32.7; 95% CI, 25.1 to 42.6; P<0.0001). By multivariable analysis, TI accounted for &19% of the variance in BP control. If TI scores were decreased &50%, that is, increasing medication dosages on &30% of visits, BP control would increase from the observed 45.1% to a projected 65.9% in 1 year. This study confirms the high rate of TI in uncontrolled hypertensive subjects. TI has a major impact on BP control in hypertensive subjects receiving regular care. Reducing TI is critical in attaining the Healthy People 2010 goal of controlling hypertension in 50% of all patients.

The article by Gangwisch et al1 in this issue of Hypertension identifies another significant health hazard associated with inadequate sleep. The authors document ≈2-fold greater risk for hypertension among adults in their fourth to sixth decades who sleep ≤5 hours each night. Whereas the independent risk of short sleep duration for developing hypertension is attenuated to ≈1.6-fold after adjusting for obesity and diabetes, short sleep duration is a risk factor for obesity and diabetes.2,3 The investigators provide plausible mechanisms linking short sleep duration to hypertension.1 Potential mechanisms include an increased blood pressure (BP) load resulting from prolongation of higher BP while awake and truncation of the BP dip characteristic of sleep. A decrease in sleep duration leads to both greater BP load1 and prolonged exposure to an activated sympathetic nervous system,4 which could accentuate structural remodeling and augment renal sodium retention. Structural changes in key target organs participating in BP regulation including the kidney, heart, and vasculature could serve to perpetuate and accelerate age-related increases in BP, especially in those at risk. In this regard, it is interesting to note a study of rapid eye movement sleep deprivation in spontaneously hypertensive, normotensive Wistar-Kyoto, and borderline hypertensive …

During the Nineteenth Annual Scientific Meeting of the American Society of Hypertension in New York, NY, on May 20, 2004, a gathering of international hypertension experts was convened to discuss far-reaching aspects of researching and managing hypertension. Dr John Laragh of Cornell University, New York, NY, USA; presided. Additional participants were, in order of participation, Jean E Sealey, DSc, New York, NY, USA; Mark C Houston, MD, Nashville, TN, USA; Haralambos Gavras, MD, Boston, MA, USA; Richard J Johnson MD, Gainesville, FL, USA; Jon D Blumenfeld, MD, New York, NY, USA; Morris Brown, MD, Cambridge, England; John B Standridge, MD, Chattanooga, TN, USA; Brent M Egan, MD, Charleston, SC, USA; Jay I Meltzer, MD, New York, NY, USA; Tatsuo Shimosawa, MD, PhD, Tokyo, Japan; Hans R Brunner, MD, Lausanne, Switzerland; and Toshiro Fujita, MD, Tokyo, Japan. The following is not verbatim but instead represents a summary of key points made over a 3-h dinner discussion.

Background: Prevalence of chest pain syndromes (CPS)-chest pain, angina pectoris, chronic angina, and pre-infarction angina/intermediate coronary syndrome (ICS)-among hypertensive patients and medical management of these disorders in primary care are not well defined.Methods: The Hypertension Initiative primary care database with 72,508 hypertensives was analyzed to characterize prevalence and management of CPS. Patients with more than one CPS were categorized by the most severe diagnosis.Its: Eleven percent of hypertensives had a CPS. Of these patients, 66% (5284) were diagnosed with chest pain only, 15% (1204) with angina, and 19% (1508) with ICS. More men than women were diagnosed with angina (18% v 4%) and ICS (21% v 10%). More women than men were diagnosed with chest pain only (86% v 61 %). African Americans received more chest pain diagnoses (71% v 62%), similar angina diagnoses (14% v 16%), and slightly fewer ICS diagnoses (15% v 22%) than whites. Most striking, women and African Americans with CPS received fewer medications than men and whites, both overall and within diagnostic categories. Prescription rates differed more by gender (male/female) than by ethnic group (white/African American) for angiotensin-converting enzyme inhibitor, diuretics, aspirin, statins, and nitrates. Hypertensives with CPS received more medications and achieved better risk factor control than non-CPS hypertensives, but the majority remained above goal levels.Conclusions: Primary care physicians treat cardiovascular risk factors relatively aggressively in hypertensives with CPS. However, substantial numbers of these patients do not reach goal levels. Demographic differences in treatment represent opportunities to reduce disparities.

The association between obesity and hypertension is well-documented but racial differences might confound this relation. The Black Pooling Project consists of nine cohort studies and includes 8,920 black women, 7,175 black men, 27,606 white women and 37,413 white men who were followed for 8 to 30 years between 1960 and 1995. The figure shows the gender-racial specific, age- and cohort-adjusted systolic blood pressure means according to levels of body mass index (BMI). After controlling for age, cholesterol, smoking status and cohort, each unit increase in BMI is associated with an increase in SBP of approximately 0.43 mmHg in black women, 1.01 mmHg in white women, 0.29 mmHg in black men and 0.79 mmHg in white men. The racial differences are significant between men and women. While blacks have a higher systolic blood pressure than whites at all levels of BMI, the difference narrows progressively with increasing BMI. The mean systolic blood pressure for black men and women were virtually all in the hypertensive range irrespective of BMI, whereas the mean systolic BP for whites reached the hypertensive range at BMI values of >30.5 for women and >32.5 for men. These data indicate that the racial disparity in blood pressure is greatest in very lean subjects and narrows progressively with increasing degrees of overweight and obesity.

We found that the DASH Eating Plan lowered blood pressure (BP) in obese hypertensives. The reduction in BP correlated inversely with the increase in plasma anti-oxidant capacity, although others have attributed BP changes to the high K+, Mg++ and/or Ca++ content of DASH. In this study, the BP lowering effects were examined of supplementing the usual diet with K+, Mg++, and fiber vs DASH in lean normotensives and obese, metabolic syndrome patients. Seven obese [BMI 37.2±5.3] volunteers, 38.7±9.2 [SD] years old, 2:AA, 5:C, 3:M, 4:F, with the metabolic syndrome and 8 lean healthy subjects [BMI 22.3±1.4, age 35.5±7.7 yrs, 2:AA, 6:C, 2:M, 6:F]. All subjects initially followed a standardized usual diet (low anti-oxidant) for 3 weeks. They were randomized to follow either the same diet supplemented with K+, Mg++, and fiber to match the content of DASH or the DASH Eating Plan for 3 weeks each followed by a 3-week crossover to the other diet. All 3 diets were isocaloric and matched for Na+ and Ca++ content. Subjects prepared their own meals. Dietary adherence was determined by digital photographs of meals and beverages and food records. At the end of each 3-weeks, 6 resting supine BP readings were taken by mercury sphygmomanometry on the left arm; the first value was deleted and last five were averaged. Compared to the usual diet, BP did not decline significantly in either group when the usual diet was supplemented with ∼2000 mg K+ and 300 mg Mg++ daily to match DASH but declined on DASH in metabolic syndrome (−5.3/−4.6 mmHg, p=0.02/0.03) but not control subjects (−3.2/−2.2 mmHg, NS/NS). The data suggest the DASH Eating Plan lowers BP more effectively in obese, metabolic syndrome patients than supplementing the usual diet with K+, Mg++ and fiber to match DASH. These findings raise the possibility that other components of the diet, e.g., antioxidant / bioflavonoids, contribute to the BP benefits of the DASH Eating Plan. See Table 1.

BACKGROUND:Although insulin resistance and metabolic syndrome are often used synonymously, concordance is not established. METHODS:Metabolic, hemodynamic, and hormonal data were analyzed on 141 patients in the Trial of Preventing Hypertension (TROPHY) Sub-Study with high-normal blood pressure (BP) (130 to 139/85 to 89 mm Hg [mean +/- SD, 133 +/- 8/85 +/- 6 mm Hg]; age, 48 +/- 9 years; body mass index 30 +/- 5 kg/m(2)). RESULTS:Fifty-three of 141 subjects (37.6%; approximately 3/8) had the metabolic syndrome based on three or more of the five risk factors (BP, waist circumference, fasting triglycerides, HDL-cholesterol, glucose). To maintain consistency in proportions, insulin resistance was defined as the upper 3/8 of the distribution on the homeostatic model assessment (HOMA), which uses fasting glucose and insulin and a modified Matsuda-DeFronzo index, based on fasting, 1- and 2-h glucose and insulin values. Among metabolic syndrome patients, 57% and 55% were in the upper 3/8 of the distribution for insulin resistance by HOMA and Matsuda-DeFronzo, respectively. Among subjects without the metabolic syndrome, 26% and 27% were insulin resistant by HOMA and Matsuda-DeFronzo criteria. The proportion of patients with metabolic syndrome and insulin resistance increased strongly and similarly with increasing body mass index. However, metabolic syndrome and insulin resistance were different compared with their respective controls in the lower 5/8 of the distribution, in waist/hip ratios, fasting and 1-h insulin, HDL-cholesterol, heart rate, and systolic BP responses to exercise and plasma renin, angiotensin, and aldosterone. CONCLUSIONS:The findings suggest that metabolic syndrome and insulin resistance are not synonymous anthropometrically, metabolically, hemodynamically, or hormonally in patients with high-normal BP.