Content uploaded by Gbenga Ogedegbe
Author content
All content in this area was uploaded by Gbenga Ogedegbe on Mar 04, 2014
Content may be subject to copyright.
A preview of the PDF is not available
2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)
Abstract and Figures
Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.
Figures - uploaded by Gbenga Ogedegbe
Author content
All figure content in this area was uploaded by Gbenga Ogedegbe
Content may be subject to copyright.
Supplementary resource (1)
Clinical Trial
February 2017
... If the target goal BP is still not achieved, reinforce lifestyle and medication, titrate meds to maximum doses, and add another medication and/or refer to an HTN specialist. Patients with compelling indications also have a written guideline to follow while prescribing antihypertensives according to JNC8 [7]. ...
... The patients' JNC8 target goal BP achievement was also assessed by the JNC8 HTN Guideline Algorithm. According to JNC8 [7] the target goal BP of patients without diabetes or CKD of ≥60 years and <60 years of age is <150/90 mmHg and <140/90 mmHg, respectively. In addition, patients of all ages with CKD with or without diabetes have a target goal BP of <140/90 mmHg. ...
... A pro forma was designed and used in the collection of the patients' sociodemographic and clinical data. The JNC8 guideline [7] was used to assess the prescribers' compliance with anti-hypertensive prescriptions and patients' achievements of the target goal BP. The Framingham 10-year CVD risk score (FRS) estimation [10] was used to estimate the patients' 10-year CVD risk level. ...
Hypertension represents a substantial risk factor for the development of cardiovascular disease (CVD), stroke, and chronic kidney disease. CVD stands as the primary cause of global mortality. This study employed a prospective cross-sectional design spanning 4 weeks. Data were collected using a pro forma designed to capture patients’ sociodemographic and clinical information. Prescribers’ adherence to anti-hypertensive prescription guidelines, as per the JNC8 guideline, and patients’ attainment of target blood pressure (BP) goals were assessed. Framingham 10-year CVD risk score estimation was employed to estimate patients’ 10-year CVD risk levels. Among the patients, 51 (59.3%) had anti-hypertensive prescriptions that adhered to the JNC8 guidelines. However, a majority, 54 (62.8%), failed to achieve their JNC8 target BP goals, and 44 (51.2%) exhibited intermediate 10-year CVD risk levels. Furthermore, 71 (98.6%) of the patients did not receive the recommended statin and/or aspirin therapy, despite its necessity. An association was found between patients’ achievement of JNC8 target BP goals and their 10-year CVD risk levels. The majority of patients received anti-hypertensive prescriptions that aligned with JNC8 guidelines. Nonetheless, most of them did not attain their JNC8 target BP goals and exhibited intermediate to high 10-year CVD risk levels.
... Therefore, the metabolic impacts of drugs selected for antihypertensive treatment must be considered in the presence of insulin resistance or T2DM (3). In line with this goal, angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are recommended by guidelines as first-line antihypertensive agents in cases of concurrent hypertension and T2DM (3)(4)(5). Telmisartan is an ARB with potent antihypertensive activity. In addition to its effect on the renin angiotensin system, telmisartan activates peroxisome proliferatoractivated receptor γ (PPARγ) (6), which is an effect that has been suggested to reduce insulin resistance among patients with concurrent disease (6,7,8). ...
... In cases of concurrent hypertension and T2DM, maintenance of normal blood pressure and glucose levels are critical to prevent microvascular and macrovascular complications (1). Since ARBs and ACE inhibitors, in addition to their antihypertensive effects, may improve insulin resistance, they are recommended as first-line antihypertensive therapies for such patients (4,5,9). We found that 12 weeks of telmisartan treatment created significant benefits in BMI (lower), systolic & diastolic blood pressure (lower), and insulin levels (higher). ...
... Within a month of starting therapy, if the desired blood pressure is not achieved, the drug dosage should be raised or a second medication should be added. 11 Treatment for hypertension is both time-consuming and expensive. Treatment costs are further influenced by the wide variety of antihypertensive drugs available and their varying levels of effectiveness. ...
Hypertension (HTN) is a chronic condition with severe complications, so early detection and effective management are essential to prevent cardiovascular events and reduce the associated economic burden. This study aims to compare the cost-effectiveness of enalapril, amlodipine, and their combination in terms of blood pressure reduction, considering overall efficacy and economic implications.
A prospective, observational cost-effectiveness analysis was conducted in 150 newly diagnosed hypertensive patients who were prescribed either enalapril (5 mg), amlodipine (5 mg), or enalapril plus amlodipine (2.5 mg each). The primary outcome was the difference in systolic and diastolic blood pressure between baseline and follow-up, as well as the evaluation of overall efficacy and cost. Based on the data, statistical analysis was carried out using ANOVA and post hoc Tukey tests for drug efficacy, and cost-effectiveness was compared using MS Excel.
After 30 days, all treatments significantly reduced systolic and diastolic blood pressure (p = 0.0001). The combination therapy with a lower dose showed superior efficacy in blood pressure reduction and was most cost-effective, requiring less expense for a 1 mmHg reduction in blood pressure compared to individual drugs with a higher dose. Quality of life assessment favored low-dose combination therapy, with fewer reported adverse effects.
The combinationof amlodipine and enalapril at a lower dose demonstrated superior cost-effectiveness, efficacy in blood pressure reduction, and a favorable impact on patients' quality of life compared to individual drugs at a higher dose. This suggests that combination therapy may be a preferred option in the management of hypertension, emphasizing the importance of considering both clinical and economic factors in treatment decisions.
... Blood pressure in the arteries is persistently elevated. Blood pressure is expressed by two measurements, systolic and diastolic, which are the maximum and minimum pressures, respectively, in the arterial system [13]. Elevated blood pressure is a major risk factor for the development of cardiovascular disease, including stroke, myocardial infarction, renal diseases, and cardiac mortality [14]. ...
... The criteria were as follows: (1) a diagnosis of diabetes; (2) use of diabetes medications or insulin; (3) fasting blood glucose ≥ 126 mg/dL; and (4) hemoglobin A1c ≥ 6.5%. Hypertension was defined as meeting one or more of the following criteria [23]: (1) a history of hypertension; ...
Background and aims
Ankle brachial index (ABI) is a risk factor for cardiovascular mortality, but it is unclear whether ABI is associated with cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). The current study aimed to evaluate the association between ABI with cardiovascular and all-cause mortality in patients with NAFLD.
Methods
We performed a cohort study using the data of the1999–2004 National Health and Nutrition Examination Survey data of adults. Mortality data were followed up to December 2015. NAFLD was defined by the hepatic steatosis index or the US fatty liver index. ABI was classified into three groups: ABI ≤ 0.9 (low value); 0.9 < ABI ≤ 1.1 (borderline value); ABI greater than 1.1 (normal value).
Results
We found that low ABI was associated with an increased risk of cardiovascular mortality in patients with NAFLD (HR: 2.42, 95% CI 1.10–5.33 for low value ABI vs normal value ABI, P for trend = 0.04), and the relationship was linearly and negatively correlated in the range of ABI < 1.4. However, low ABI was not associated with all-cause mortality in patients with NAFLD. Stratified by cardiovascular disease, ABI remains inversely correlated with cardiovascular mortality in NAFLD patients without cardiovascular disease. Stratified by diabetes, ABI is inversely correlated with cardiovascular mortality in NAFLD patients regardless of diabetes status.
Conclusions
Low ABI is independently associated with higher cardiovascular mortality in NAFLD cases. This correlation remains significant even in the absence of pre-existing cardiovascular disease or diabetes.
Importance
Patient portals are increasingly used for patient-clinician communication and to introduce interventions aimed at improving blood pressure control.
Objective
To characterize patient portal use among patients with hypertension managed in primary care.
Design, Settings, and Participants
This retrospective cohort study used electronic health records linked with patient portal log file data from a large, diverse Midwestern health care system. Patients with hypertension who had a primary care visit from January 1, 2021, to December 31, 2021, were included. The first visit in 2021 was considered the baseline visit; patient portal engagement was evaluated during the following year. Multivariate logistic regressions, presented as odds ratios (ORs) and 95% CIs, were used to evaluate associations between patient characteristics and patient portal engagement, adjusting for potential confounders.
Exposures
Primary exposures included 4 sociodemographic factors routinely collected in the electronic health record: race and ethnicity, insurance, preferred language, and smoking status.
Main Outcomes and Measures
Indicators of patient engagement with the patient portal included accessing the patient portal at least once, accessing the portal within 7 days of at least 50.0% of primary care physician (PCP) visits, frequent logins (<28 vs ≥28), messaging (<2 vs ≥2), and sharing home blood pressure readings.
Results
Among 366 871 patients (mean [SD], 63.5 [12.6] years), 52.8% were female, 3.4% were Asian, 7.8% were Hispanic, 19.7% were non-Hispanic Black, 66.9% were non-Hispanic White, and 2.3% were of other race or ethnicity. During the 1-year study period starting in 2021, 70.5% accessed the patient portal at least once, 60.2% accessed around the time of their PCP visits, 35.7% accessed the portal frequently, 28.9% engaged in messaging, and 8.7% shared home blood pressure readings. Compared with White patients, non-Hispanic Black and Hispanic patients had lower odds of any access (Black: OR, 0.53; 95% CI, 0.52-0.54; Hispanic: OR, 0.66; 95% CI, 0.64-0.68), access around PCP visit time (Black: OR, 0.49; 95% CI, 0.48-0.50; Hispanic: OR, 0.62; 95% CI, 0.60-0.64), frequent access (Black: OR, 0.56; 95% CI, 0.55-0.57; Hispanic: OR, 0.71; 95% CI, 0.69-0.73), and messaging (Black: OR, 0.63; 95% CI, 0.61-0.64); Hispanic: OR, 0.71; 95% CI, 0.69-0.73).
Conclusions and Relevance
This cohort study of patients with hypertension found clear sociodemographic disparities in patient portal engagement among those treated in primary care. Without special efforts to engage patients with portals, interventions that use patient portals to target hypertension may exacerbate disparities.
Purpose
To evaluate the impact of surgical intervention on long-term renal outcomes for adult patients with congenital ureteropelvic junction obstruction (UPJO).
Methods
We queried service members diagnosed with UPJO from the United States Military Health System electronic health records from 2005 to 2020. We assessed demographic, laboratory, radiology, surgical intervention, and outcome data. We evaluated the impact of surgical intervention on renal function based on the estimated glomerular filtration rate (eGFR), hypertension (HTN, defined as any prescription for blood pressure [BP] medication and/or average of two BP readings ≥ 130/80 mmHg more than 2 weeks apart), and changes in renal excretory function on radionuclide scans.
Results
We identified 108 individuals diagnosed with congenital UPJO; mean follow-up of 7 years. Mean age at diagnosis was 25 years; 95% male; 69% White, 15% Black. At diagnosis, median BP was 130/78 mmHg and mean eGFR 93 ml/min/1.73m². Subsequently, 85% had pyeloplasty and 23% had stent placement. There were no significant differences in mean eGFR pre- and post-intervention (94 vs. 93 ml/min/1.73m², respectively; p = 0.15) and prevalence of defined HTN (59% vs. 61%, respectively; p = 0.20). Surgical intervention for right-sided UPJO significantly reduced the proportion of patients with delayed cortical excretion (54% pre vs. 35% post, p = 0.01) and T½ emptying time (35 min vs. 19 min, p = 0.009). Similar trends occurred with left-sided UPJO but were not significant.
Conclusion
Surgical intervention was not associated with significant differences in the long-term outcomes of kidney function and HTN prevalence in our young adult cohort. However, renal excretory function improved on radionuclide scans.
This study aimed to explore the potential correlation between atherosclerotic cardiovascular disease (ASCVD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). We enrolled 6540 patients with T2DM who were receiving chronic disease management for hypertension, hyperglycemia, and hyperlipidemia in Chengyang District of Qingdao. Among them, 730 had ASCVD (ASCVD group), which 5810 did not (N-ASCVD group). The results showed significantly higher levels of age, blood glucose, glycosylated hemoglobin (HbA1c), systolic blood pressure, ASCVD family history, female proportion, and DR incidence in the N-ASCVD group. Additionally, the glomerular filtration rate was significantly lower in the ASCVD group. Logistic regression analysis revealed a positive correlation between DR and ASCVD risk. DR was further categorized into 2 subtypes, nonproliferative DR (NPDR) and proliferative DR (PDR), based on e lesion severity. Interestingly, only the PDR was associated with ASCVD. Even after accounting for traditional ASCVD risk factors such as age, sex, and family history, PDR remained associated with ASCVD, with a staggering 718% increase in the risk for patients with PDR. Therefore, there is a strong association between ASCVD and DR in individuals with T2DM, with PDR particularly exhibiting an independent and positive correlation with increased ASCVD risk.
Background
Noncommunicable diseases (NCDs) account for nearly 75% of all deaths in Tamil Nadu. The government of Tamil Nadu has initiated several strategies to control NCDs under the Tamil Nadu Health Systems Reform Program (TNHSRP). We aimed to estimate the prevalence of NCD risk factors and determine the predictors of diabetes and hypertension, which will be helpful for planning and serve as a baseline for evaluating the impact of interventions.
Methods
A state-wide representative cross-sectional study was conducted among 18-69-year-old adults in Tamil Nadu in 2020. The study used a multi-stage sampling method to select the calculated sample size of 5780. We adapted the study tools based on WHO’s STEPS surveillance methodology. We collected information about sociodemographic factors, NCD risk factors and measured blood pressure and fasting capillary blood glucose. The predictors of diabetes and hypertension were calculated using generalised linear models with 95% confidence intervals (95% CI).
Results
Due to the COVID-19 pandemic lockdown, we could cover 68% (n = 3800) of the intended sample size. Among the eligible individuals surveyed (n = 4128), we had a response rate of 92%. The mean age of the study participants was 42.8 years, and 51% were women. Current tobacco use was prevalent in 40% (95% CI: 33.7–40.0) of men and 7.9% (95% CI: 6.4–9.8) of women. Current consumption of alcohol was prevalent among 39.1% (95% CI: 36.4–42.0) of men. Nearly 28.5% (95% CI: 26.7–30.4) of the study participants were overweight, and 11.4% (95% CI: 10.1–12.7) were obese. The prevalence of hypertension was 33.9% (95% CI: 32.0–35.8), and that of diabetes was 17.6% (95% CI: 16.1–19.2). Older age, men, and obesity were independently associated with diabetes and hypertension.
Conclusion
The burden of NCD risk factors like tobacco use, and alcohol use were high among men in the state of Tamil Nadu. The prevalence of other risk factors like physical inactivity, raised blood pressure and raised blood glucose were also high in the state. The state should further emphasise measures that reduce the burden of NCD risk factors. Policy-based and health system-based interventions to control NCDs must be a high priority for the state.
Background
Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.
Methods
18 790 patients, from 26 countries, aged 50–80 years (mean 61·5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure ⩽90 mm Hg, 6264 to ⩽85 mm Hg, and 6262 to ⩽80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.
Findings
Diastolic blood pressure was reduced by 20·3 mm Hg, 22·3 mm Hg, and 24·3 mm Hg, in the ⩽90 mm Hg, ⩽85 mm Hg, and ⩽80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82·6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86·5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group ⩽80 mm Hg compared with target group ⩽90 mm Hg (p for trend=0·005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0·03) and all myocardial infarction by 36% (p=0·002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0·001).
Interpretation
Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82·6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.
The Hypertension Detection and Follow-up Program (HDFP) previously reported a 16.9% reduction in all-cause mortality among its Stepped Care (SC) group, relative to the community-treated Referred Care (RC) group. The current report compares cerebrovascular disease (CV) morbidity and mortality in the SC and RC populations. The SC five-year stroke incidence (1.9 per 100 persons) is significantly lower than that found among the RC (2.9 per 100 persons). Reductions in stroke rates among SC were experienced for all race-sex groups, all diastolic blood pressure strata, all ages, and among those with or without evidence of long-standing hypertension. Comparisons of the CV death rates for SC (1.06 per 1,000 persons) and RC (1.91 per 1,000 persons) with those obtained for the general US population (0.83 per 1,000 persons) indicate that the CV death rate decreased in the SC hypertensive population to a level approaching that of the general US population.
Four hundred fifty-two stroke survivors with recumbent blood pressures ranging from 140 to 220 mm Hg systolic and 90 to 115 mm Hg diastolic (average, 167/100 mm Hg) were followed up for a mean period of three years; half the patients received an antihypertensive drug and half received placebo. The hypothesis that antihypertensive therapy for hypertensive stroke survivors would alter the stroke recurrence rate was not statistically supported by the data. No statistically significant reduction occurred in the number of endpoints due to cardiovascular disease except for congestive heart failure, in which the drug-treated group exhibited a statistically significant reduction.
Myocardial infarction, sudden cardiac death, cerebrovascular accidents, blood pressure control and treatment tolerability were studied in a randomized double-blind trial conducted in 6357 men and women aged 40-64 years with uncomplicated essential hypertension (diastolic blood pressures 100-125 mmHg). At the start of the trial 3185 patients received treatment based on a beta-blocker (oxprenolol while in the remaining 3172 placebo replaced oxprenolol. Supplementary drugs, excluding beta-blockers, were used as necessary in both treatment groups, with the aim of reducing diastolic pressure to 95 mmHg or less. Patients were followed for 3-5 years, a total of 25 651 patient years at risk. In most respects the two groups fared equally well; sudden death (relative risk [RR] 1.08; 95% confidence interval [CI] 0.68 and 1.72 myocardial infarction (RR 0.83; Cl 0.59 and 1.16) and cerebrovascular accident (RR 0. 97; Cl 0.64 and 1.47) rates were similar. Beta-blocker based therapy was associated with significantly lower average blood pressures, earlier ECG normalization, less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension. Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability. In smokers the cardiac event rate was doubled. We propose that beta-blocker treatment effects depend on smoking status, with a significant interaction benefiting non-smoking men. Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events. Proportional hazards analysis also underlines the importance of other cardiovascular risk factors. The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients.
The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease aims to provide guidance on blood pressure management and treatment for all non-dialysis-dependent CKD patients and kidney transplant recipients. Guideline development followed an explicit process of evidence review and appraisal. Treatment approaches are addressed in each chapter and guideline recommendations are based on systematic reviews of relevant trials. Appraisal of the quality of the evidence and the strength of recommendations followed the GRADE approach. Ongoing areas of controversies and limitations of the evidence are discussed and additional suggestions are also provided for future research.
The Australian therapeutic trial in mild hypertension, which was undertaken to investigate the value of pharmacological treatment, showed significant benefit in treated subjects. The control (placebo) group in this study comprised 1943 persons with mild hypertension who were not given antihypertensive drug treatment. They had regular visits for measurements of blood-pressure and were evaluated at intervals to detect the occurrence of trial end-points (essentially cardiovascular or cerebrovascular events). This paper reports the changes in blood-pressure and occurrence of trial end-points in these untreated subjects who entered the study between June, 1973, and December, 1975; observations were made up to March, 1979. In all subjects of the Australian therapeutic trial in mild hypertension, mean pressures for the two screening visits were within the range 95-109 mm Hg for diastolic blood-pressure phase V (DBP) and <200 mm Hg for systolic blood-pressure (SBP). In the 1943 control (placebo) subjects mean blood-pressures fell from 158/102 mm Hg at the first screening visit to 144/91 mm Hg 3 years later. At that time pressures remained within the mild hypertension range in 32%, had risen above it in 12%, and had fallen below in 48%. Trial end-points (ischaemic heart disease or cerebrovascular accident) occurred in 8%. The outcome was related to the level of initial pressure but not to other characteristics measured at entry. The mean initial pressures of 22 subjects who experienced a cerebrovascular event were higher than those of a matched group with no hypertensive complications, but the 88 subjects who experienced ischaemic-heart-disease events had initial pressures similar to those in a matched control group. The trial end-point was related to the average DBP of subjects throughout the trial in those with average DBP ≥95 mm Hg, and at those levels subjects on active treatment had a higher incidence than subjects of the placebo group with the same DBP level. For those with average DBP below 95 mm Hg the incidence of trial end-points was not related to blood-pressure level or treatment. 16% of placebo subjects in this mild hypertensive population had a mean DBP of less than 95 mm Hg at the first three visits. If this were taken as an indication to withhold drug treatment, 3 years later one-quarter of them (4% of all subjects) would be found to be hypertensive or to have experienced a trial end-point, and thus inappropriately untreated, while the other 12% would have pressures below 95 mm Hg and have had no trial end-point.