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Background: The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated reductions in major cardiovascular disease events and mortality with an intensive systolic blood pressure (SBP) goal intervention. However, a detailed description of the blood pressure intervention, antihypertensive medication usage, blood pressure levels, and rates and predictors of blood pressure control has not been reported previously., Methods: Hypertensive participants (n=9361) 50 years and older with elevated cardiovascular disease risk were randomized 1:1 to SBP goal <120 mm Hg or SBP goal <140 mm Hg. Guideline-recommended antihypertensive medications and dosing were provided at no cost. Intensive group participants were started on at least 2 medications, and medications were adjusted monthly until SBP goal was achieved, if feasible. Standard group participants were treated to achieve SBP 135 to 139 mm Hg., Results: Baseline blood pressure (median±interquartile range) was 138±19/78±16 mm Hg. For intensive group participants, percent at goal rose from 8.9% at baseline to 52.4% at 6 months and average antihypertensive medications rose from 2.2 to 2.7; SBP was <120 mm Hg in 61.6% and <130 mm Hg in 80.0% at their final visit. For the standard group participants, percent at goal rose from 53.0% at baseline to 68.6% at 6 months, while antihypertensive medications fell from 1.9 to 1.8. From 6 to 36 months, median SBP was stable at 119±14 mm Hg for intensive and 136±15 mm Hg for standard participants, with stable numbers of medications. Few predictors of SBP control were found in multiple regression models., Conclusions: These results may inform and help replicate the benefits of SPRINT in clinical practice., Registration: URL: http://www., Clinicaltrials: gov; Unique identifier: NCT01206062.

The SPRINT (Systolic Blood Pressure Intervention Trial) results have influenced clinical practice but have also generated discussion regarding the validity, generalizability, and importance of the findings. Following the SPRINT primary results manuscript in 2015, additional results and analyses of the data have addressed these concerns. The primary objective of this article is to respond to key questions that have been raised.

Recent publications have stated that the blood pressure (BP) measurement technique used in SPRINT (Systolic Blood Pressure Intervention Trial) was unattended. However, the SPRINT protocol does not address the issue of attendance. A survey was conducted immediately after SPRINT closeout visits were completed to inquire whether BP measurements were usually attended or unattended by staff. There were 4082 participants at 38 sites that measured BP after leaving the participant alone the entire time (always alone), 2247 at 25 sites that had personnel in the room the entire time (never alone), 1746 at 19 sites that left the participant alone only during the rest period (alone for rest), and 570 at 6 sites that left the participant alone only during the BP readings (alone for BP measurement). Similar systolic and diastolic BPs within randomized groups were noted during follow-up at the majority of visits in all 4 measurement categories. In the always alone and never alone categories, the intensive group had a similarly reduced risk for the primary outcome compared with the standard group (hazard ratio, 0.62; 95% confidence interval, 0.51-0.76 and hazard ratio, 0.64; 95% confidence interval, 0.46-0.91, respectively; pairwise interaction P value, 0.88); risk was not significantly reduced for the intensive group in the smaller alone-for-rest and the alone-for-BP-measurement categories. Similar BP levels and cardiovascular disease risk reduction were observed in the intensive group in SPRINT participants whether the measurement technique used was primarily attended or unattended., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062., (© 2018 American Heart Association, Inc.)

Competing Interests: Conflicts of Interest/Disclosures: None for Drs. Ard, Arnett, Carter, Cooper, Cutler, Davis, Desvigne-Nickens, Diez Roux, Einhorn, Gavini, Go, Kimmel, Mensah, Miller, Mills, Ogedegbe, Rahman, Thomas, Tobin, Whelton, Wright, and Yoon. Dr. Appel has an institutional conflict of interest with Healthways, Inc. Dr. Cushman is an investigator for institutional grants from Eli Lilly and Boerhinger-Ingelheim, and has provided unpaid services for Takeda. Dr. Freedman and Wake Forest University Health Sciences have filed for a patent related to APOL1 genetic testing. Dr. Freedman receives grant support from Novartis Pharmaceuticals and is a consultant for Ionis Pharmaceuticals. Dr. Ferdinand is a consultant for Amgen, Sanofi, Eli Lilly, and Boehringer Ingleheim. Dr. Margolis served on an advisory board for Novartis Pharmaceuticals. Dr. Muntner receives research support from Amgen, Inc. Dr. Navar is an investigator for institutional grants from Sanofi and Regeneron pharmaceuticals. Dr. Taylor is on an advisory board for Amgen, Inc and for Alnylam Pharmaceuticals. The views expressed in this article do not necessarily represent the American Medical Association; National Institutes of Health; Centers for Disease Control and Prevention; or US Department of Health and Human Services.

Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes mellitus, its prevalence, the effect of intensive versus standard systolic blood pressure (BP) targets on incident OH, and its prognostic significance are unclear. In 4266 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial, seated BP was measured 3×, followed by readings every minute for 3 minutes after standing. Orthostatic BP change, calculated as the minimum standing minus the mean seated systolic BP and diastolic BP, was assessed at baseline, 12 months, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization or death and the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, occurred at ≥1 time point in 20% of participants. Neither age nor systolic BP treatment target (intensive, <120 mm Hg versus standard, <140 mm Hg) was related to OH incidence. Over a median follow-up of 46.9 months, OH was associated with increased risk of total death (hazard ratio, 1.61; 95% confidence interval, 1.11-2.36) and heart failure death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17-2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes mellitus and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events., (© 2016 American Heart Association, Inc.)

Main results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial were published in December 2002. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, published in May 2003, recommended thiazide-type diuretics as initial pharmacological treatment alone or in combination with another drug in most patients with hypertension. To assess changes from before to after these publications, we compared antihypertensive medication prescriptions filled by patients who initiated pharmacological antihypertensive treatment in a large managed care organization during 3 time periods: (1) July 1, 2001, to June 30, 2002 (before these publications; n=1354); (2) July 1, 2003, to June 30, 2004 (to assess short-term changes; n=1542); and (3) July 1, 2004, to June 30, 2005 (to assess extended changes; n=1865). The percentage of patients initiating antihypertensive treatment with a thiazide-type diuretic increased from 30.6% to 39.4% (P<0.001) between 2001-2002 and 2003-2004, and the increase was maintained at 36.5% in 2004-2005 (P<0.001 compared with 2001-2002 and P=0.33 compared with 2003-2004). Among patients without diabetes mellitus, renal disease, a history of myocardial infarction, or heart failure, the percentage initiating pharmacological antihypertensive treatment with a thiazide-type diuretic increased from 33.1% in 2001-2002 to 43.4% in 2003-2004 (P<0.001) and remained increased (41.0%) in 2004-2005 (P<0.001 and P=0.23 compared with 2001-2002 and 2003-2004, respectively). Despite a sustained increase in the use of thiazide-type diuretics, this study indicates that an opportunity exists to increase adherence to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines.

This study assesses trends in hypertension prevalence, blood pressure distributions and mean levels, and hypertension awareness, treatment, and control among US adults, age >or=18 years, between the third National Health and Nutrition Examination Survey (1988-1994) and the 1999-2004 National Health and Nutrition Examination Survey, a period of approximately 10 years. The age-standardized prevalence rate increased from 24.4% to 28.9% (P<0.001), with the largest increases among non-Hispanic women. Depending on gender and race/ethnicity, from one fifth to four fifths of the increase could be accounted for by increasing body mass index. Among hypertensive persons, there were modest increases in awareness (P=0.04), from 68.5% to 71.8%. The rate for men increased from 61.6% to 69.3% (P=0.001), whereas the rate for women did not change significantly. Rates remained higher for women than for men, although the difference narrowed considerably. Improvements in treatment and control rates were larger: 53.1% to 61.4% and 26.1% to 35.1%, respectively (both P<0.001). The greatest increases occurred among non-Hispanic white men and non-Hispanic black persons, especially men. Mexican American persons showed improvement in treatment and control rates, but these rates remained the lowest among race/ethnic subgroups (47.4% and 24.3%, respectively). Among all of the race/ethnic groups, women continued to have somewhat better awareness, treatment, and control, except for control rates among non-Hispanic white persons, which became higher in men. Differences between non-Hispanic black and white persons in awareness, treatment, and control were small. These divergent trends may translate into disparate trends in cardiovascular disease morbidity and mortality.

This study aims to estimate the absolute number of persons with hypertension (the hypertension burden) and time trends using data from the National Health and Nutrition Examination Survey of United States resident adults who had hypertension in 1999 to 2000. This information is vitally important for health policy, medical care, and public health strategy and resource allocation. At least 65 million adults had hypertension in 1999 to 2000. The total hypertension prevalence rate was 31.3%. This value represents adults with elevated systolic or diastolic blood pressure, or using antihypertensive medications (rate of 28.4%; standard error [SE], 1.1), and adults who otherwise by medical history were told at least twice by a physician or other health professional that they had high blood pressure (rate of 2.9%; SE, 0.4). The number of adults with hypertension increased by approximately 30% for 1999 to 2000 compared with at least 50 million for 1988 to 1994. The 50 million value was based on a rate of 23.4% for adults with elevated blood pressure or using antihypertensive medications and 5.5% for adults classified as hypertensive by medical history alone (28.9% total; P<0.001). The approximately 30% increase in the total number of adults with hypertension was almost 4-times greater than the 8.3% increase in total prevalence rate. These trends were associated with increased obesity and an aging and growing population. Approximately 35 million women and 30 million men had hypertension. At least 48 million non-Hispanic white adults, approximately 9 million non-Hispanic black adults, 3 million Mexican American, and 5 million other adults had hypertension in 1999 to 2000.

Although group characteristics are known to influence average blood pressure response to changes in salt intake, predictability of individual responses is less clear. We examined variability and consistency of individual systolic blood pressure responses to changes in salt intake in 188 participants who ate the same diet at higher, medium, and lower (140, 104, 62 mmol/d) sodium levels for 30 days each, in random order, after 2 weeks of run-in at the higher sodium level. Regarding variability in systolic blood pressure changes over time, changes from run-in to higher sodium (no sodium level change) ranged from -24 to +25 mm Hg; 8.0% of participants decreased > or =10 mm Hg. Regarding variability in systolic blood pressure response to change in sodium intake, with higher versus lower sodium levels (78-mmol sodium difference), the range of systolic blood pressure change was -32 to +17 mm Hg; 33.5% decreased > or =10 mm Hg. Regarding consistency of response, systolic blood pressure change with run-in versus lower sodium was modestly correlated with systolic blood pressure change with higher versus medium sodium; systolic blood pressure change with higher versus lower sodium was similarly correlated with run-in versus medium sodium (combined Spearman r=0.27, P=0.002). These results show low-order consistency of response and confirm that identifying individuals as sodium responders is difficult. They support current recommendations for lower salt intake directed at the general public rather than "susceptible" individuals as one of several strategies to prevent and control adverse blood pressures widely prevalent in the adult population.

The angiotensinogen gene has been linked to essential hypertension and increased blood pressure. A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels. To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction, 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus. Participants had diastolic blood pressures between 83 and 89 mm Hg and were randomized in a 2x2 factorial design to sodium reduction, weight loss, combined intervention, or usual care groups. Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension (44.6%) compared with those with the GG genotype (31.5%), with a relative risk of 1.4 (95% confidence interval [0.87, 2.34], test for trend across all 3 genotypes, P=0.10). In contrast, the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype (relative risk=0.57 [0.34, 0.98] versus usual care) but not for persons with the GG genotype (relative risk=1.2 [0.79, 1.81], test for trend P=0.02). Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes (P=0.01), with greater net blood pressure reduction in those with the AA genotype (-2.2 mm Hg) than those with the GG genotype (+1.1 mm Hg). A similar trend across the 3 genotypes for net systolic blood pressure reduction (-2.7 for AA versus -0.2 mm Hg for GG) was not significant (P=0.17). Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction. We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension.

The objective of this study was to describe secular trends in the distribution of blood pressure and prevalence of hypertension in US adults and changes in rates of awareness, treatment, and control of hypertension. The study design comprised nationally representative cross-sectional surveys with both an in-person interview and a medical examination that included blood pressure measurement. Between 6530 and 13,645 adults, aged 18 through 74 years, were examined in each of four separate national surveys during 1960-1962, 1971-1974, 1976-1980, and 1988-1991. Protocols for blood pressure measurement varied significantly across the surveys and are presented in detail. Between the first (1971-1974) and second (1976-1980) National Health and Nutrition Examination Surveys (NHANES I and NHANES II, respectively), age-adjusted prevalence of hypertension at > or = 160/95 mm Hg remained stable at approximately 20%. In NHANES III (1988-1991), it was 14.2%. Age-adjusted prevalence at > or = 140/90 mm Hg peaked at 36.3% in NHANES I and declined to 20.4% in NHANES III. Age-specific prevalence rates have decreased for every age-sex-race subgroup except for black men aged 50 and older. Age-adjusted mean systolic pressures declined progressively from 131 mm Hg at the NHANES I examination to 119 mm Hg at the NHANES III examination. The mean systolic and diastolic pressures of every sex-race subgroup declined between NHANES II and III (3 to 6 mm Hg systolic, 6 to 9 mm Hg diastolic). During the interval between NHANES II and III, the threshold for defining hypertension was changed from 160/95 to 140/90 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to estimate the current prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the US adult population. The study used a cross-sectional survey of the civilian, noninstitutionalized population of the United States, including an in-home interview and a clinic examination, each of which included measurement of blood pressure. Data for 9901 participants 18 years of age and older from phase 1 of the third National Health and Nutrition Examination Survey, collected from 1988 through 1991, were used. Twenty-four percent of the US adult population representing 43,186,000 persons had hypertension. The age-adjusted prevalence in the non-Hispanic black, non-Hispanic white, and Mexican American populations was 32.4%, 23.3%, and 22.6%, respectively. Overall, two thirds of the population with hypertension were aware of their diagnosis (69%), and a majority were taking prescribed medication (53%). Only one third of Mexican Americans with hypertension were being treated (35%), and only 14% achieved control in contrast to 25% and 24% of the non-Hispanic black and non-Hispanic white populations with hypertension, respectively. Almost 13 million adults classified as being normotensive reported being told on one or more occasions that they had hypertension; 51% of this group reported current adherence to lifestyle changes to control their hypertension. Hypertension continues to be a common finding in the general population. Awareness, treatment, and control of hypertension have improved substantially since the 1976-1980 National Health and Nutrition Examination Survey but continue to be suboptimal, especially in Mexican Americans.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase I of the Trials of Hypertension Prevention was a multicenter, randomized trial of the feasibility and efficacy of seven nonpharmacologic interventions, including sodium reduction, in lowering blood pressure in 30- to 54-year-old individuals with a diastolic blood pressure of 80 to 89 mm Hg. Six centers tested an intervention designed to reduce dietary sodium to 80 mmol (1800 mg)/24 h with a total of 327 active intervention and 417 control subjects. The intervention consisted of eight group and two one-to-one meetings during the first 3 months, followed by less-intensive counseling and support for the duration of the study. The mean net decrease in sodium excretion was 43.9 mmol/24 h at 18 months. Women had lower sodium intake at baseline and were therefore more likely to decrease to less than 80 mmol/24 h. Black subjects were less likely to decrease to less than 80 mmol/d, independent of sex or baseline sodium excretion. The mean (95% confidence interval) net decrease associated with treatment was -2.1 (-3.3, -0.8) mm Hg for systolic blood pressure and -1.2 (-2.0, -0.3) mm Hg for diastolic blood pressure at 18 months (both P < .01). Multivariate analyses indicated a larger systolic blood pressure effect in women (-4.44 versus -1.23 mm Hg in men), adjusted for age, race, baseline blood pressure, and baseline 24-hour urinary sodium excretion (P = .02). Dose-response analyses indicated an adjusted decrease of -1.4 mm Hg for systolic blood pressure and -0.9 mm Hg for diastolic blood pressure for a decrease of 100 mmol/24 h in 18-month sodium excretion. These results support the utility of sodium reduction as a population strategy for hypertension prevention and raise questions about possible differences in dose response associated with gender and initial level of sodium intake.

We report the effect of weight changes of the type of antihypertensive medication prescribed in a trial of the relative efficacy of drug and dietary measures in mild hypertension. The Trial of Antihypertensive Interventions and Management studied 878 mildly hypertensive individuals randomly assigned, in a 3 x 3 design, to no diet change, weight loss, or a low sodium-high potassium diet and to placebo, 25 mg chlorthalidone, or 50 mg atenolol. The type of drug prescribed affected weight change with all diets. The drug effect on weight change, present in all groups at 6 months, was most pronounced in those randomly assigned to the weight loss diet, where the placebo group lost 4.4 kg, the atenolol group lost 3.0 kg, and the chlorthalidone group lost 6.9 kg. The group differences were attenuated but persisted at 24 months. We suggest that the antihypertensive drug prescribed affects the success of a conjoint weight loss program and speculate that the difference between the drugs may be due to their intrinsic effects on the sympathetic nervous system and related metabolic changes.

To test for effects on systolic and diastolic blood pressure and to provide precise estimates of their magnitude, we conducted an overview of randomized clinical trials that aimed to reduce the intake of sodium in human subjects. We excluded from pooled analyses trials with confounded designs, those that compared intake levels beyond the usual range in the population, and those without published reports. Two reviewers abstracted information in duplicate and differences were reconciled. Twenty-three trials with outcome data from an aggregate of 1,536 subjects were included. Data were pooled both separately for hypertensive and normotensive subjects and for all trials combined. With the use of sample size weighting, blood pressure reductions (net of controls) were 4.9 +/- 1.3/2.6 +/- 0.8 mm Hg (systolic and diastolic, respectively, with 95% confidence limits) in hypertensive subjects and 1.7 +/- 1.0/1.0 +/- 0.7 mm Hg in normotensive subjects. The combined blood pressure reductions were 2.9 +/- 0.8/1.6 +/- 0.5 mm Hg. These changes were associated with mean reduction of urinary sodium excretion ranging from 16 to 171 mmol/24 hr for individual trials. A dose-response relation across trials was found, both in normotensive and in hypertensive subjects. These results indicate that sodium reduction lowers mean blood pressure in both hypertensive and normotensive individuals for periods of at least several months. The findings are highly consistent with results of observational epidemiological studies and have implications for preventive strategies of blood pressure control.

Selected portions of the workshop's closing discussion are summarized. Major ongoing clinical trials of antihypertensive drug treatment are described. Some recommendations offered by workshop participants for future research directions are summarized.

We reviewed the designs and major results of 17 large-scale, controlled, clinical trials that reported the effects of drug treatment for hypertension on morbidity or mortality. Seven trials conducted in study populations with more-severe hypertension (diastolic blood pressures 100-120 mm Hg or higher), including the more-severe stratum of the Veterans Administration Trial, showed large reductions in stroke, other "hypertensive" events, and, in one trial, total mortality. Of 11 trials in populations with less-severe hypertension (diastolic blood pressures predominantly below 105 mm Hg), including the less-severe stratum of the Veterans Administration Trial, nine met the criteria for pooling of results. Among the aggregate 43,000 patients in the nine trials who were followed up for an average of 5.6 years, mean diastolic blood pressure reduction was 5.8 mm Hg, and a significant 11% reduction in total mortality was observed. This benefit was largely attributable to a 38% reduction in fatal strokes; nonfatal strokes were similarly reduced. Coronary heart disease mortality was 8% lower in drug treatment than in control groups, but this difference was not significant. A similar result was observed for combined coronary mortality and nonfatal myocardial infarction. A possible explanation for the inconclusive result regarding coronary end points was an adverse trend, observed in several trials, in a subgroup with baseline resting electrocardiographic abnormalities. Because all the trials except the propranolol arm of the Medical Research Council trial used drug regimens based on thiazide-like diuretic agents, and because there are now several new drug classes proposed as initial therapy, additional large-scale clinical trials may need to be considered.

Three recently concluded large randomized clinical trials have compared the preventive effects of diuretic agents and beta-blockers in the treatment of approximately 22,000 subjects with hypertension. In the Medical Research Council trial, bendrofluazide (10 mg daily) was compared with a dose of propranolol (as much as 240 mg daily), a nonselective beta-blocker without intrinsic sympathomimetic activity. Two selective beta-blockers, atenolol (100 mg daily) and metoprolol (200 mg daily), were compared with bendrofluazide (5-10 mg daily) and hydrochlorothiazide (50-100 mg daily) in the Heart Attack Primary Prevention in Hypertension trial. In the International Prospective Primary Prevention Study in Hypertension, 160 mg of slow-release oxprenolol, a beta-blocker with intrinsic sympathomimetic activity, was compared with a diuretic-based regimen not containing beta-blockers. In each trial, similar reductions in mean diastolic blood pressure were achieved with diuretic and beta-blocker treatment that lasted for several years. All-cause mortality and fatal and nonfatal stroke and coronary event rates were also similar in the treatment groups. Thus, it appears that beta-blockers are as effective as diuretic agents in improving survival and in preventing major morbid events. Regarding cigarette smoking and stroke incidence, observations based on post hoc subgroup analyses of the Medical Research Council trial were not supported by subgroup findings in the Heart Attack Primary Prevention in Hypertension and the International Prospective Primary Prevention Study in Hypertension trials, and these observations should not form the basis for any treatment recommendations.

The effects of prolonged differences in diastolic blood pressure (DBP) on the risks of stroke and of coronary heart disease (CHD) were estimated from nine major prospective observational studies involving about 420,000 men and women who were followed up for intervals of 6-25 years. The results indicate that a prolonged difference of about 6 mm Hg in DBP was associated with approximately 37% fewer strokes and 23% fewer CHD deaths and nonfatal myocardial infarctions. The effects of equivalent reductions in DBP produced by antihypertensive drug treatment but maintained for only a few years have been estimated in several overviews of randomized trials involving a total of 30,000-40,000 patients. The results of the overviews indicate that treatment reduced the risk of stroke by about 40%, suggesting that most or all the long-term potential benefits for stroke due to lower DBP were achieved within about 3 years of beginning treatment. The risks of nonfatal myocardial infarction and CHD death may have been reduced by about 10% among patients allocated to active treatment; the 95% confidence limits for the difference ranged from about zero to about 20%. Whatever the true effect of treatment on CHD, it would appear somewhat less than the difference in risk estimated from the observational studies for a prolonged difference in DBP of the same size. This apparent shortfall in benefit may reflect a long time-course for changes in DBP to have their full effects on CHD, possible adverse side effects of the principal trial treatments, or both.