Barry L. Carter

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.

These guidelines have been written to provide a straightforward approach to managing hypertension in the community. We have intended that this brief curriculum and set of recommendations be useful not only for primary care physicians and medical students, but for all professionals who work as hands-on practitioners. We are aware that there is great variability in access to medical care among communities. Even in so-called wealthy countries there are sizable communities in which economic, logistic, and geographic issues put constraints on medical care. And, at the same time, we are been reminded that even in countries with highly limited resources, medical leaders have assigned the highest priority to supporting their colleagues in confronting the growing toll of devastating strokes, cardiovascular events, and kidney failure caused by hypertension. Our goal has been to give sufficient information to enable health care practitioners, wherever they are located, to provide professional care for people with hypertension. All the same, we recognize that it will often not be possible to carry out all of our suggestions for clinical evaluation, tests, and therapies. Indeed, there are situations where the most simple and empirical care for hypertension—simply distributing whatever antihypertensive drugs might be available to people with high blood pressure—is better than doing nothing at all. We hope that we have allowed sufficient flexibility in this statement to enable responsible clinicians to devise workable plans for providing the best possible care for patients with hypertension in their communities. Note: This preferably should be a fasting sample so that a fasting blood glucose level and more accurate lipid profiles can be obtained. Several lifestyle interventions have been shown to reduce blood pressure. Apart from contributing to the treatment of hypertension, these strategies are beneficial in managing most of the other cardiovascular risk factors. In patients with hypertension that is no more severe than stage 1 and is not associated with evidence of abnormal cardiovascular findings or other cardiovascular risks, 6 to 12 months of lifestyle changes can be attempted in the hope that they may be sufficiently effective to make it unnecessary to use medicines. However, it may be prudent to start treatment with drugs sooner if it is clear that the blood pressure is not responding to the lifestyle methods or if other risk factors appear. Also, in practice settings where patients have logistical difficulties in making regular clinic visits, it might be most practical to start drug therapy early. In general, lifestyle changes should be regarded as a complement to drug therapy rather than an alternative. Starting treatment: (see the algorithm in the Figure). Treatment with drugs should be started in patients with blood pressures >140/90 mm Hg in whom lifestyle treatments have not been effective. (Note: As discussed earlier in Section 12 on Nonpharmacologic Treatment, drug treatment can be delayed for some months in patients with stage 1 hypertension who do not have evidence of abnormal cardiovascular findings or other risk factors. In settings where healthcare resources are highly limited, clinicians can consider extending the nondrug observation period in uncomplicated stage 1 hypertensive patients provided there is no evidence for an increase in blood pressure or the appearance of cardiovascular or renal findings). In patients with stage 2 hypertension (blood pressure ≥160/100 mm Hg), drug treatment should be started immediately after diagnosis, usually with a 2-drug combination, without waiting to see the effects of lifestyle changes. Drug treatment can also be started immediately in all hypertensive patients in whom, for logistical or other practical reasons, the practitioner believes it is necessary to achieve more rapid control of blood pressure. The presence of other cardiovascular risk factors should also accelerate the start of hypertension treatment. Note: There is an assumption, unless otherwise stated, that all drugs in a class are similar to each other. We only mention individual agents if they have an important property that is not shared by the others in its class. Table 2 provides a list of commonly used antihypertensive drugs and their doses. Note: Thiazides plus β-blockers are also an effective combination for reducing blood pressure, but since both classes can increase blood glucose concentrations this combination should be used with caution in patients at risk for developing diabetes. The authors of this statement acknowledge that there are insufficient published data from clinical trials in hypertension to create recommendations that are completely evidence-based, and so inevitably some of our recommendations reflect expert opinion and experience. We also should point out that because of the major differences in resources among points of care it is not possible to create a uniform set of guidelines. For this reason we have written a broad statement on the management of hypertension and have not presumed to anticipate the conditions or shortfalls that might exist in particular communities. We expect that experts who are familiar with local circumstances will feel free to use their own judgment in modifying our recommendations and to create practical instructions to help guide front-line practitioners in providing the best care possible. The authors of this statement would welcome comments and suggestions from colleagues. We recognize that in this initial version of the guidelines there will probably be omissions, redundancies, and inaccuracies. Please feel free to get in touch with us either by letters to the Journal or by personal communication. This statement was written under the sponsorship of the American Society of Hypertension and the International Society of Hypertension. In addition, the Asia Pacific Society of Hypertension has endorsed these guidelines. The statement was prepared without any external funding. The work and time of the authors was provided by them entirely on a volunteer basis. MAW: Research funding: Medtronics. Consulting: Boehringer-Ingelheim, Novartis, Daichi Sankyo, Takeda, Forest. Speaker: Daiichi Sankyo, Takeda, Forest. ELS: Research Funding: Canadian Institutes of Health Research, Canada Research Chairs program of CIHR/Government of Canada, Servier France. Consultant: Servier, Novartis. Speaker: Forest Canada, Pfizer Japan. WBW: Research Funding: National Institutes of Health. Consulting: Safety Committees (DSMB, CEC, Steering Committees); Ardea Biosciences, Inc.; AstraZeneca; Dendreon, Forest Research Institute, Inc.; Roche; St. Jude's Medical, Takeda Global Research, Teva Neuroscience. SM, LHL, JGK, BJM, DLC, JCC, RRJC, ST, AJR, AES, RMT: No conflicts of interest. JMF: Research Funding: Novartis, Medtronic. Consultant: Novartis, Medtronic, Back Beat Hypertension. BLC: Research Funding: NIH and VA. VSR: Consultant: Medtronic, Daiichi-Sankyo, Forest. DK: Research Funding: Medtronic. RT: Research Funding: NIH. Consultant: Medtronic, Janssen, Merck, GSK. JC: Research Funding and Speaker: Servier in relation to ADVANCE trial and Post-trial study. GLB: Research Funding: Takeda. Consultant: Takeda, AbbVie, Daiichi-Sankyo, Novartis, CVRx, Medtronic, Relypsa, Janssen, BMS. JW: Consultant and Speaker: Boehringer-Ingelheim, MSD, Novartis, Omron, Pfizer, Servier, and Takeda. JDB: Research and Consultant: CVRx. DS: Research: Medtronic, CVRx. Consultant: Takeda, UCB, Novartis, Medtronic, CVRx. Speaker: Takeda. SBH: Speaker: Novartis, Servier.

STATEMENTOF PURPOSE: These guidelines have been written to provide a straightforward approach to managing hypertension in the community. We have intended that this brief curriculum and set of recommendations be useful not only for primary care physicians and medical students, but for all professionals who work as hands-on practitioners. We are aware that there is a great variability in access to medical care among communities. Even in so-called wealthy countries, there are sizable communities in which economic, logistic, and geographic issues put constraints on medical care. And, at the same time, we are been reminded that even in countries with highly limited resources, medical leaders have assigned the highest priority to supporting their colleagues in confronting the growing toll of devastating strokes, cardiovascular events, and kidney failure caused by hypertension. Our goal has been to give sufficient information to enable healthcare practitioners, wherever they are located, to provide professional care for people with hypertension. All the same, we recognize that it will often not be possible to carry out all of our suggestions for clinical evaluation, tests, and therapies. Indeed, there are situations in which the most simple and empirical care for hypertension-simply distributing whatever antihypertensive drugs might be available to people with high blood pressure-is better than doing nothing at all. We hope that we have allowed sufficient flexibility in this statement to enable responsible clinicians to devise workable plans for providing the best possible care of hypertension in their communities. We have divided this brief document into the following sections: 1. General introduction, 2. Epidemiology, 3. Special issues with black patients (African ancestry), 4. How is hypertension defined?, 5. How is hypertension classified?, 6. Causes of hypertension, 7. Making the diagnosis of hypertension, 8. Evaluating the patient, 9. Physical examination, 10. Tests, 11. Goals of treating hypertension, 12. Nonpharmacologic treatment of hypertension, 13. Drug treatment of hypertension, 14. Brief comments on drug classes, 15. Treatment-resistant hypertension.

National guidelines and a recent clinical trial have supported the use of thiazide diuretics as the preferred initial pharmacological treatment for hypertension. However, evidence from this and other clinical trials have also found an increased incidence of new onset diabetes among those patients receiving thiazide diuretics. The mechanisms responsible for the increased incidence of diabetes with thiazide diuretics have not been fully elucidated. This article provides a review of intervention studies that included data on the relation between thiazide-induced hypokalemia and glucose intolerance. We conducted a literature search from 1966 to June 2004 to identify clinical trials using thiazide diuretics where the metabolic effects on potassium and glucose are reported. A total of 59 clinical trials constituting 83 thiazide diuretic study arms were identified. Trial size, length, type of thiazide diuretic, and dose varied substantially among the studies. The association between average changes in potassium and glucose in the study arms is considered jointly in a weighted statistical model. The Pearson's correlation coefficient, weighted by study sample size, for the relationship between glucose and potassium was -0.54 (95% CI, -0.67 to -0.36; P < 0.01). A sensitivity analysis, which considered subset analyses and effect of covariates, as well as inverse-variance weighting, supported this finding. These data suggest that thiazide-induced hypokalemia is associated with increased blood glucose. Treatment of thiazide-induced hypokalemia may reverse glucose intolerance and possibly prevent the future development of diabetes.

Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients. Chlorthalidone has significantly reduced stroke and cardiovascular end points in several landmark trials; however, hydrochlorothiazide remains favored in practice. Most clinicians assume that the drugs are interchangeable, but their antihypertensive effects at lower doses have not been directly compared. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory blood pressure (BP) monitoring, was assessed at baseline and week 8, along with standard office BP readings every 2 weeks. Thirty patients completed the first active treatment period, whereas 24 patients completed both. An order-drug-time interaction was observed with chlorthalidone; therefore, data from only the first active treatment period was considered. Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day (24-hour mean = -12.4+/-1.8 mm Hg versus -7.4+/-1.7 mm Hg; P=0.054; nighttime mean = -13.5+/-1.9 mm Hg versus -6.4+/-1.8 mm Hg; P=0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day (-15.7+/-2.2 mm Hg versus -4.5+/-2.1 mm Hg; P=0.001); however, by week 8, reductions were statistically similar (-17.1+/-3.7 versus -10.8+/-3.5; P=0.84). Within recommended doses, chlorthalidone is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced by 24-hour ambulatory BPs. These differences were not apparent with office BP measurements.