Hypertension Guidelines in Need of Guidance

The medical communities around the world that have yearned for about a decade for updated “guidance” on the management of hypertension got what they wished, or did not wish—plentiful guidelines in the year 2013. Hypertension guidelines (and advisories) poured in from the European Society of Cardiology/European Society of Hypertension (ESC/ESH), the American Heart Association/American College of Cardiology report from the members of the Joint National Committee 8 (JCN 8), the minority report from some members of JNC 8, and the American Society of Hypertension/International Society of Hypertension (ASH/ISH).1-5 The multitude of guidelines from respected professional bodies and individuals have caused, in my opinion, needless confusion bordering on chaos. While various guidelines and recommendations have a common goal of reducing the global burden of cardiovascular disease (CVD) by effective treatment of hypertension, they differ modestly on the cutoff points for target blood pressure (BP) levels and in special populations. The conflicting recommendations from various but well-meaning sources created temporary confusion and doubts in the minds of healthcare professionals and public health experts. While the differences may be small, the noise level was significant enough to question whether we need any more hypertension guidelines at all? Systemic hypertension remains an important cause of premature morbidity and excessive global mortality.6-9 In most countries, hypertension has become the chief cause of disability and death. Despite the universal acknowledgement that hypertension should be diagnosed and aggressively treated, BP control rates around the world are abysmally low and shameful. Since hypertension truly is a “silent killer” and remains undetected, CVD progression defies boundaries. Rampant CVD exerts enormous health and economic burdens on the individual, family, society, and nation as a whole. In other words, the adverse impact of hypertension extends beyond the individual and should be viewed as a contagion. With ample evidence that high levels of BP are detrimental and that hypertension can be effectively treated, it is inappropriate now to give mixed signals to the medical community and health policy makers. From diverse sources of information that patients get in this digital age, it is extremely risky to imply that BP level targets should be loosened. I have argued in various forums that the main problem in patients with hypertension is “high” BP not “low” BP. We should be more worried about hypertension, not hypotension. Surely, one would avoid excessive or unwanted degree of BP lowering in patients with hypertension; it needs only common sense, not guideline committees. JNC 8 was dissolved by the National Heart, Lung, and Blood Institute before it submitted the report. Therefore, some members of JNC 8 presented the recommendations as individual members, not as a committee.3 Their recommendations, despite so much effort and work, are not endorsed by any professional organization or scientific body. The recommendations made by the individual members of JNC 83 are very restrictive in scope and of possible academic interest to experts who seek evidence-based strategies, but they are not of much value to healthcare providers who treat hypertension in the real world setting. One illustrative example: the guidelines from the past members of JNC 8 suggest a threshold of >150/90 mm Hg for patients 60 years or older, whereas the ASH/ISH guidelines5 apply that level of BP threshold for patients older than 80 years. The suggestion for age-dependent criteria for hypertension management made by the erstwhile JNC 8 were made on the basis of cherry-picked studies in the elderly. The recommendation was based on the observation that a systolic BP <140 mm Hg was not superior to that <150 mm Hg. However, in the studies they cited, no harm was induced at a systolic BP <140 mm Hg. In contrast, the ASH/ISH guidelines suggest a threshold of <140/90 mm Hg for patients between the ages of 60 and 80 years on the basis of data from 3 large studies—the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE), and Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trials.5 The threshold for <150 mm Hg (as opposed to <140 mm Hg) only applies if you are aged 80 years or older. This has been a contentious point. Who can really argue that for a 60-year-old patient, a systolic BP level <140 mm Hg is awkward!! The proposal made by the JNC 8 panel members that the target BP for patients older than 60 should be >150/90 mm Hg has the potential for misinterpretation and laxity at a time when there is a global cry and a clarion call to improve the hypertension control rates in all ages. The elderly group is of paramount importance because of high risk, disease vulnerability, and high rates of “resistant” hypertension.10 The burden of proof provided by JNC 8 members was insufficient to reduce the burden of CVD. The BP targets recommended by 2013 European guidelines are less aggressive than before, but for most patients the goal should be <140/90 mm Hg, which makes sense. For hypertensive patients with diabetes, the diastolic BP target is <85 mm Hg, which also makes sense.11 Let us not quibble over 80 mm Hg or 85 mm Hg. The minority view from members of the JNC 8 panel4 offers substantial evidence that a systolic BP <140 mm Hg in patients older than 60 years confers enormous health benefits, particularly in the absence of diabetes or chronic kidney disease (CKD). A target BP level of <140 mm Hg for individuals younger than 80 years is recommended by at least 5 national and international professional organizations.1, 2, 5, 12, 13 The lack of benefit from aggressive treatment of hypertension in the elderly was seen in two studies—the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly (JATOS)14 and the Valsartan in Elderly Isolated Systolic Hypertension (VALISH) trial.15 However, these studies were vastly underpowered and had low composite event rates (125 strokes and 67 coronary events). In contrast, an elderly hypertension study (the Felodipine Event Reduction [FEVER] trial),17 which was considered by the ESC/ESH panel but not by the JNC 8 members, reported safety and significant therapeutic benefits in patients treated to a systolic BP of 137 mm Hg (Table). Effective treatment for hypertension in the elderly is not rocket science, but the benefits are spectacular in limiting the occurrence of stroke and heart failure. Any CVD: 331 Strokes:120 Deaths:431 HR: 0.61 P=.046 CVD or renal events: 172 Deaths: 17 Rate per 1000 patient-years: 22.6 vs 22.7 P=.99 CVD or renal events: 99 Deaths: 54 HR: 0.89 (CI, 0.60–1.31) P=.383 Any CVD: 575 Strokes: 428 Deaths: 263 HR: 0.73 P=.0019 In sum, the scope of recommendations made by the JNC 8 panel members is limited by the narrow principle of evidence-based and selective criteria. The panel acknowledged that its report is not comprehensive and does not cover many aspects of hypertension evaluation and treatment such as ambulatory BP monitoring, variability of BP, workup, and nonpharmacologic therapy. Many patients older than 60 years have obesity and hyperlipidemia, which increases the CVD risk from hypertension. Hence, it is important to aim for optimal BP goals in this population. The ASH/ISH guidelines (Figure) suggest different (and broader) drug choices for initial therapy compared with the recommendations of JNC 8 panel members. While the guidelines from JNC 8 panel members on drug selection appear restrictive, the ASH/ISH therapeutic suggestions truly provide guidance on managing hypertension in the “community.” While the JNC 8 panelists' views on β-blockers are acceptable, their recommendations on thiazides as a homogenous class are unwarranted. There should have been mention about other diuretics. Moreover, other than in the elderly, the initial choice of thiazides in younger patients is not based on evidence. In addition, chronic exposure to thiazides increases the risk of new-onset diabetes. There should have been an objective statement on the place of aldosterone antagonists in the treatment of resistant hypertension. The so-framed “evidence-based dosing” of antihypertensive drugs is a faulty concept; one titrates the drug dosage to meet the intended therapeutic target level. Therefore, there is no sensation about dosing. We are not talking about chemotherapy. The ASH/ISH guidelines are comprehensive and include steps for evaluation, diagnosis, and management of hypertension in the community, taking into consideration “totality” of the evidence from numerous published clinical trials of the past decade. The ASH/ISH guidelines provide a user-friendly approach that can be easily followed by the healthcare professionals at the point-of-contact with hypertensive patients. These guidelines are practical enough to suggest that practitioners may wish to achieve lower-than-recommended BP targets at their discretion if the therapy is well tolerated. This is a courageous statement—we are, after all, healthcare providers, not journalists. The ASH/ISH statement comments on situations that matter to the practitioners—resistant hypertension, white-coat hypertension, 24-hour ambulatory BP monitoring, cerebrovascular disease, dementia, CKD, diabetes, microalbuminuria, coronary artery disease, heart failure, and sleep apnea. The ASH/ISH guidelines do not recommend special targets for black patients other than stating that they have severe forms of hypertension that require closer surveillance to achieve target BP levels. As expected, there is much overlap between various guidelines, except for age thresholds (60 years vs 80 years) and systolic BP targets (140 mm Hg vs 150 mm Hg). The best way to move forward (not lateral) is to apply differing guidelines in a complimentary fashion to render “individualized” treatment. No single size fits all.In conclusion, the guidelines/statements offer knowledge base but should not be viewed as a substitute for sound clinical reasoning in making diagnostic and therapeutic decisions to benefit the patient as an individual, not as a group. The time has come for an everlasting, single “global” guideline document leaving room for regional/cultural differences and ground realities. One noncontroversial recommendation, however, is that hypertension be treated aggressively to prevent unrelenting excessive morbidity and mortality from CVD. Hypertension is serious business. Individuals with hypertension are at high risk for a variety of systemic complications that lead to significant morbidity and excessive mortality. The global medical community should view hypertension as a merciless killer. At a time when we have an urgent task to enhance patient adherence to nonpharmacologic and pharmacologic therapies, introduction of controversial recommendations does not help the cause. Unfortunately, some recently released hypertension guidelines do not present recommendations on the benefit to risk ratios of therapeutic intervention or inaction. Guidelines generally address broad populations, but it is the practitioner who has to decide about individual patients. Although the rigorous process of writing guidelines is complex, and a painful undertaking, inappropriate recommendations based on incomplete information can result in unintended alarming ramifications. Which side should you look first before crossing the street—left? or right? As far as I am concerned, unless level IA “evidence” is provided to the contrary, I will look on both sides before crossing, lest I be run over by a fast-moving guideline. The author thanks the excellent secretarial support provided by Ms. Madhawii in assembling this commentary.