Thomson

Clinical Practice Guidelines for the Management ofHypertension in the CommunityA Statement by the American Society of Hypertensionand the International Society of Hypertension Michael A. , Ernesto L. , William B. , Samuel MannLars H. ,John G. John M. Flack, Barry L. CarterBarry J. MatersonC. Venkata S. ,Debbie L. CohenJean-Claude , Roger R. , Sandra TalerDavid ,Raymond , John ChalmersAgustin J. , George L. Jiguang ,Aletta E. SchutteJohn D. Rhian M. , Dominic , and Stephen B. Harrap STATEMENT OF PURPOSE 5. How is hypertension classified?6. Causes of hypertension T hese guidelines have been written to provide a 7. Makingthediagnosisofhypertension straightforward approach to managing hypertension 8. Evaluating the patient in the community. We have intended that this brief 9. Physical examination curriculum and set of recommendations be useful not only for primary care physicians and medical students, but for allprofessionals who work as hands-on practitioners.
We are aware that there is a great variability in access to Journal of Hypertension 2014, 32:3–15 medical care among communities. Even in so-called weal- aState University of New York, Downstate College of Medicine, Brooklyn, New York, thy countries, there are sizable communities in which USA, bDepartment of Medicine, Sir Mortimer B. Davis Jewish General Hospital, McGill economic, logistic, and geographic issues put constraints University, Montreal, Canada, cCalhoun Cardiology Center, University of Connecticut, on medical care. And, at the same time, we are been Farmington, Connecticut, dDepartment of Medicine, Weil Cornell College of Medi-cine, New York, New York, USA, eDepartment of Public Health and Clinical Medicine, reminded that even in countries with highly limited resour- Umea University, Umea, Sweden, fCardiovascular Associates, Virginia Beach, Virginia, ces, medical leaders have assigned the highest priority to gDepartment of Medicine, Wayne State University, Detroit, Michigan, hDepartment of supporting their colleagues in confronting the growing toll Pharmacy Practice and Science, University of Iowa, Iowa City, Iowa, iDepartment ofMedicine, University of Miami Miller School of Medicine, Miami, Florida, USA, of devastating strokes, cardiovascular events, and kidney jMediCiti Institutions, Hyderabad, India, kDepartment of Medicine, University of failure caused by hypertension.
Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA, lState UniversitySchool of Medicine, mHypertension Center of Haiti, Port-au-Prince, Haiti, nDepartment Our goal has been to give sufficient information to of Medicine, Mayo Clinic, Rochester, Minnesota, oJersey Shore University Medical enable healthcare practitioners, wherever they are located, Center, Neptune, New Jersey, pHypertension Center, University of Pennsylvania, to provide professional care for people with hypertension.
Philadelphia, Pennsylvania, USA, qGeorge Institute for Global Health, University ofSydney, Sydney, New South Wales, Australia, rArterial Hypertension and Metabolic All the same, we recognize that it will often not be possible Unit, University Hospital, Favaloro Foundation, Buenos Aires, Argentina, sASH Com- to carry out all of our suggestions for clinical evaluation, prehensive Hypertension Center, University of Chicago Medicine, Chicago, Illinois, tests, and therapies. Indeed, there are situations in which USA, tThe Shanghai Institute of Hypertension, Shanghai Jiaotong University School ofMedicine, Shanghai, China, uHypertension in Africa Research Team, North West the most simple and empirical care for hypertension – University, Potchefstroom, South Africa, vDepartment of Medicine, University of simply distributing whatever antihypertensive drugs might Rochester Medical Center, Rochester, New York, USA, wInstitute of Cardiovascularand Medical Sciences, University of Glasgow, Glasgow, Lanarkshire, UK, xVirginia be available to people with high blood pressure – is better Commonwealth University, Richmond, Virginia, USA and yDepartment of Physiology, than doing nothing at all. We hope that we have allowed University of Melbourne, Melbourne, Australia sufficient flexibility in this statement to enable responsible Correspondence to Michael A. Weber, MD, Division of Cardiovascular Medicine, State clinicians to devise workable plans for providing the best University of New York, Downstate College of Medicine, 450 Clarkson Avenue, Box97, Brooklyn, NY 11203, USA. Tel: +1 714 815 7430; e-mail: possible care of hypertension in their communities.
We have divided this brief document into the following Received 31 October 2013 Accepted 31 October 2013 ß 2013 The International Society of Hypertension (ISH).
In cooperation with the American Society of Hypertension these guidelines were 1. General introduction co-published in the Journal of Clinical Hypertension under the copyright of WileyPeriodicals, Inc.
J Hypertens 32:3 –15 ß 2013 Wolters Kluwer Health Lippincott Williams & 3. Special issues with black patients (African ancestry) 4. How is hypertension defined? Journal of Hypertension Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Weber et al.
11. Goals of treating hypertension
A higher proportion of black people are sensitive to 12. Nonpharmacologic treatment of hypertension the blood pressure-raising effects of salt in the diet 13. Drug treatment of hypertension than white patients, and this – together with obesity, 14. Brief comments on drug classes especially among women – may be part of the expla- 15. Treatment-resistant hypertension nation for why young black people tend to haveearlier and more severe hypertension than othergroups.

Black patients with hypertension are particularly vulnerable to strokes and to hypertensive kidney
About one-third of adults in most communities in disease. They are three to five times as likely as whites the developed and developing world have hyper- to have renal complications and end-stage kidney
Hypertension is the most common chronic condition
There is a tendency for black patients to have dealt with by primary care physicians and other differing blood pressure responses to the available antihypertensive drug classes: they usually respond
Most patients with hypertension have other risk fac- well to treatment with calcium channel blockers tors as well, including lipid abnormalities, glucose (CCBs) and diuretics, but have smaller blood pres- intolerance or diabetes, a family history of early car- sure reductions with angiotensin-converting enzyme diovascular events, obesity, and cigarette smoking.
(ACE) inhibitors, angiotensin receptor blockers (ARBs),
The success of treating hypertension has been limited, and b-blockers. However, appropriate combina- and despite well established approaches to diagnosis tion therapies provide powerful antihypertensive and treatment, in many communities fewer than half responses that are similar in black and white patients.
of all hypertensive patients have their blood pressures Most patients will require more than one antihyperten- sive drug to maintain blood pressure control.
4. HOW IS HYPERTENSION DEFINED?
There is a close relationship between blood pressure
Most major guidelines recommend that hypertension levels and the risk of cardiovascular events, strokes, be diagnosed when a person's SBP is 140 mmHg or and kidney disease.
higher, or their DBP is 90 mmHg or higher, or both,
The risk of these outcomes is lowest at a blood on repeated examination. The SBP is particularly pressure of around 115/75 mmHg.
important and is the basis for diagnosis in most
Above 115/75 mmHg, for each increase of 20 mmHg in systolic blood pressure (SBP) or 10 mmHg in dias-
These numbers apply to all adults older than 18, tolic blood pressure (DBP), the risk of major cardio- though for patients aged 80 or older, a SBP up to vascular and stroke events doubles.
150 mmHg is now regarded as acceptable.

The high prevalence of hypertension in the com-
The goal of treating hypertension is to reduce blood munity is currently being driven by two phenomena: pressure to levels below the numbers used for making the increased age of our populations, and the grow- the diagnosis.
ing prevalence of obesity, which is seen in develop-
These definitions are based on the results of major ing as well as in developed countries. In many clinical trials that have shown the benefits of treating communities, a high dietary salt intake is also a people to these levels of blood pressure. Even though, major factor.
as discussed earlier, a blood pressure of 115/75 is
The main risk of events is tied to an increased SBP; ideal, there is no evidence to justify treating hyper- after age 50 or 60, DBP may actually start to decrease, tension down to such a low level.
but systolic pressure continues to rise throughout life.

We do not have sufficient information about younger This increase in SBP and decrease in DBP with aging adults (between 18 and 55) to know whether they reflect the progressive stiffening of the arterial circu- might benefit from defining hypertension at a level lation. The reason for this effect of aging is not well below 140/90 mmHg (e.g., 130/80 mmHg) and treat- understood, but high SBPs in older people represent a ing them more aggressively than older adults. Thus, major risk factor for cardiovascular and stroke events guidelines tend to use 140/90 mmHg for all adults and kidney disease progression.
(up to 80 years old). Even so, at a practitioner'sdiscretion, lower blood pressure targets may be 3. SPECIAL ISSUES WITH BLACK considered in young adults, provided the therapy PATIENTS (AFRICAN ANCESTRY) is well tolerated.

Some recent guidelines have recommended diagnos-
Hypertension is a particularly common finding in tic values of 130/80 mmHg for patients with diabetes black people.
or chronic kidney disease. However, the clinical
Hypertension occurs at a younger age and is often benefits of this lower target have not been established more severe in terms of blood pressure levels in black and so these patients should be treated to below patients than in whites.
140/90 mmHg.
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5. HOW IS HYPERTENSION CLASSIFIED? bias of the observers. If the auscultatory method isused, the first and fifth Korotkoff sounds (the appear-
For people with SBPs between 120 and 139 mmHg, or ance and disappearance of sounds) will correspond to diastolic pressures between 80 and 89 mmHg, the the SBP and DBP.
term ‘prehypertension' can be used. Patients with this
Arm cuffs are preferred. Cuffs that fit on the finger or condition should not be treated with blood pressure wrist are often inaccurate and should, in general, not medications. However, they should be encouraged to make lifestyle changes in the hope of delaying or even
It is important to ensure that the correct size of arm preventing progression to hypertension.
cuff is used [in particular, a wider cuff in patients with
Stage 1 hypertension: patients with SBP 140– large arms (>32 cm circumference)].
159 mmHg, or DBP 90–99 mmHg.

At the initial evaluation, blood pressure should be
Stage 2 hypertension: SBP 160 mmHg or higher, or measured in both arms; if the readings are different, DBP 100 mmHg or higher.
the arm with the higher reading should be used formeasurements thereafter.
6. CAUSES OF HYPERTENSION
The blood pressure should be taken after patients have emptied their bladders. Patients should be Primary hypertension: seated with their backs supported and with theirlegs resting on the ground and in the uncrossed
About 95% of adults with high blood pressure have position for 5 min.
primary hypertension (sometimes called essential hy-
The patient's arm being used for the measurement should be at the same level as the heart, with the arm
The cause of primary hypertension is not known, resting comfortably on a table.
although genetic and environmental factors that
It is preferable to take two readings, 1–2 min apart, affect blood pressure regulation are now being and use the average of these measurements.

It is useful to also obtain standing blood pressures
Environmental factors include excess intake of salt, (usually after 1 min and again after 3 min) to check for obesity, and perhaps sedentary lifestyle.
postural effects, particularly in older people.

Some genetically related factors could include inap-
In general, the diagnosis of hypertension should propriately high activity of the renin–angiotensin– be confirmed at an additional patient visit, usually aldosterone system and the sympathetic nervous sys- 1–4 weeks after the first measurement. On both tem and susceptibility to the effects of dietary salt on occasions, the SBP should be 140 mmHg or higher, blood pressure.
or the diastolic pressure 90 mmHg or higher, or both,
Another common cause of hypertension is due to in order to make a diagnosis of hypertension.
stiffening of the aorta with increasing age. This causes
If the blood pressure is very high (for instance, a SBP hypertension referred to as isolated or predominant of 180 mmHg or more), or if available resources are systolic hypertension characterized by high systolic not adequate to permit a convenient second visit, the pressures (often with normal diastolic pressures) that diagnosis and, if appropriate, treatment can be started is found primarily in elderly people.
after the first set of readings that demonstrate hyper- Secondary hypertension:
For practitioners and their staffs not experienced in
This pertains to the relatively small number of measuring blood pressures, it is necessary to receive patients, about 5%, of all hypertension, where the appropriate training in performing this important cause of the high blood pressure can be identified and sometimes treated.

Some patients may have blood pressures that are
The main types of secondary hypertension are chronic high in the clinic or office, but are normal elsewhere.
kidney disease; renal artery stenosis; excessive This is often called ‘white coat hypertension.' If it is aldosterone secretion; pheochromocytoma and sleep suspected, consider getting home blood pressure readings (see below) to check this possibility.

A simple screening approach for identifying secon- Another approach is to use ambulatory blood pres- dary hypertension is given later.
sure monitoring, if it is available. In this procedure,the patient wears an arm cuff connected to a devicethat automatically measures and records blood 7. MAKING THE DIAGNOSIS OF pressures at regular intervals, usually over a 24-h
It can be helpful to measure blood pressures at
Blood pressure can be measured by either a conven- home. If available, the electronic device is simpler tional sphygmomanometer using a stethoscope or by to use and probably more reliable than the sphyg- an automated electronic device. The electronic momanometer. The average of blood pressures device, if available, is preferred because it provides measured over 5–7 days, if possible in duplicate at more reproducible results than the older method and each measurement, can be a useful guide for diag- is not influenced by variations in technique or by the nostic and treatment decisions.
Journal of Hypertension Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Weber et al.
8. EVALUATING THE PATIENT absence of clinical history. It is vital that smoking bediscontinued. In most cases antiplatelet drugs
Often a high blood pressure is only one of several should be used.
cardiovascular risk factors that require attention.

Before starting treatment of hypertension, it is very Why is this important? This condition is commonly useful to evaluate the patient more thoroughly. The associated with hypertension and is associated with three methods are personal history, physical examin- an increased risk of cardiovascular events. Certain ation, and selective testing.
medications such as ARBs and ACE inhibitors shouldbe used, particularly if there is evidence for albumi-nuria or chronic kidney disease. Good blood pres- sure control, often requiring the addition of CCBs
Ask carefully about previous cardiovascular events and diuretics, is also important in these patients.
because they often suggest an increased probability of future events that can influence the choice of drugs Why is this important? Special treatments are often for treating the hypertension and will also require required for these patients and their use may make more aggressive treatment of all cardiovascular risk it possible to improve blood pressure control as factors. Also ask patients whether they have pre- well as the other findings of this condition.
viously been told they have hypertension and, ifrelevant, their responses to any drugs they might have
Ask about other risk factors Why is this important? Risk factors can affect blood Important previous events include the following: pressure targets and treatment selection for the I. Stroke or transient ischemic attacks or dementia hypertension. Thus, knowing about age, dyslipide- Why is this information important? For patients with mias, microalbuminuria, gout, or family histories of these previous events, it may be necessary to hypertension and diabetes can be valuable. Cigarette include particular drug types in their treatment, smoking is a risk factor that must be identified so for instance, ARBs or ACE inhibitors, CCBs, and that counseling can be given about stopping this diuretics, as well as drugs for low-density lipopro- dangerous habit.
tein (LDL) cholesterol (statins), and antiplatelet
Ask about concurrent drugs I. Commonly used drugs (for indications unrelated to II. Coronary artery disease, including myocardial treating hypertension) can increase blood pressure infarctions, angina pectoris, and coronary revas- and, therefore, should be stopped if possible. These include NSAIDs used for arthritis and pain relief; Why is this important? Certain medications would some tricyclic and other types of antidepressants; be preferred, for instance b-blockers, ACE inhibi- older high-dose oral contraceptives; migraine medi- tors or ARBs, statins, and antiplatelet agents cations; cold remedies (e.g., pseudoephedrine). In addition, some patients may be taking herbal medi- III. Heart failure or symptoms suggesting left ventric- cations, folk remedies, or drugs of addiction (e.g., ular dysfunction (shortness of breath, edema) cocaine), which can increase blood pressure.
Why is this important? Certain medications wouldbe preferred in such patients, including ARBs or 9. PHYSICAL EXAMINATION ACE inhibitors, b-blockers, diuretics, and spirono-lactone. Also, certain medications should be
At the first visit, it is important to do a complete avoided such as nondihydropyridine CCBs (vera- physical examination because often getting care for pamil, diltiazem) in patients with systolic heart hypertension is the only contact that people have with a medical practitioner.
IV. Chronic kidney disease
Measuring the blood pressure: this has been discussed Why is this important? Certain medications would be preferred, including ACE inhibitors or ARBs
Document the weight and height and calculate body (though these two drug classes should not be mass index (BMI). This can be done by going online to prescribed in combination with each other), statins, Google, searching BMI and entering the patient's and diuretics [loop diuretics may be required if the weight and height as instructed estimated glomerular filtration rate (eGFR) is below 30] and blood pressure treatment targets might be is this important? This helps to set targets for weight lower (130/80 mmHg) if albuminuria is present.
loss and, as discussed later, knowing whether a Note: In patients with more advanced kidney dis- patient is obese or not obese might affect the choice ease the use of some of these drugs often requires of hypertension treatment. It should be noted that the the expertise of a nephrologist.
risk of cardiovascular events, including stroke, para- V. Peripheral artery disease doxically may be higher in lean hypertensive people Why is this important? This finding suggests than in obese.
advanced arterial disease that may also exist in
Waist circumference. Why is this important? Inde- the coronary or brain circulations, even in the pendent of weight, this helps determine whether a Volume 32
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January 2014 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
patient has the metabolic syndrome and is at risk of type have baseline values. Also, obese people can 2 diabetes. Risk is high when this measurement is more have fatty liver disorders that should be identified than 102 cm in men, or more than 88 cm in women.
and considered in overall management.

Signs of heart failure. Why is this important? This diagnosis strongly influences the choice of hyper- tension therapy. Left ventricular hypertrophy can be Why is this important? If present, this can be suspected by chest palpation, and heart failure can be indicative of kidney disease and is also associated indicated by distended jugular veins, rales on chest with an increased risk of cardiovascular events.
examination, an enlarged liver and peripheral edema.
Ideally, an albumin/creatinine ratio should be
Neurologic examination. Why is this important? This obtained, but even dipstick evidence of albumi- may reveal signs of previous stroke and affect nuria (þ1 or greater) is helpful.
II. Red cells, white cells
Eyes: If possible, the optic fundi should be checked Why are these important? Positive findings can be for hypertensive or diabetic changes and the areas indicative of urinary tract infections, kidney stones around the eyes for findings such as xanthomas.
or other potentially serious urinary tract con-
Pulses: It is important to check peripheral pulses; if ditions, including bladder tumors.
they are diminished or absent, this can indicate per-
Electrocardiogram ipheral artery disease.
Why is this important? The ECG can help identifyprevious myocardial infarctions or left atrial andventricular hypertrophy (which is evidence of tar- get organ damage and indicative of the need for good control of blood pressure). An ECG might also Note: This preferably should be a fasting sample so identify cardiac arrhythmias such as atrial fibrilla- that a fasting blood glucose level and more accurate tion (which would dictate the use of certain drugs) lipid profiles can be obtained.
or such conditions as heart block (which would contraindicate certain drugs, e.g., b-blockers, rate- Why is this important? There is a special emphasis slowing CCBs). An echocardiogram, if available, on potassium: high levels can suggest renal dis- can also be helpful in diagnosing left ventricular ease, particularly if creatinine is elevated. Low hypertrophy and quantifying the ejection fraction in values can suggest aldosterone excess. In patients with suspected heart failure, although this addition, illnesses associated with severe diarrhea test is not routine in hypertensive patients.
are common in some communities and can causehypokalemia and other electrolyte changes.
11. OVERALL GOALS OF TREATMENT II. Fasting glucose concentration Why is this important? If elevated, this could be I. The goal of treatment is to manage hypertension and indicative of impaired glucose tolerance, or if to deal with all the other identified risk factors for sufficiently high, of diabetes. If available, HbA1C cardiovascular disease, including lipid disorders, should be measured to further assess an elevated glucose intolerance or diabetes, obesity, and smok- glucose level and help in making a diagnosis.
III. Serum creatinine and blood urea nitrogen II. For hypertension, the treatment goal for SBP usually Why are these important? Increased creatinine is less than 140 mmHg and for DBP less than levels are usually indicative of kidney disease; 90 mmHg. In the past, guidelines have recom- creatinine is also used in formulae for eGFR.
mended treatment values of less than 130/80 mmHg When appropriate, use formulae designed for for patients with diabetes, chronic kidney disease, eGFR calculations in patients of African ancestry.
and coronary artery disease. However, evidence to support this lower target in patients with these Why are these important? Elevated LDL choles- conditions is lacking, so the goal of less than140/ terol or low values of high-density lipoprotein 90 mmHg should generally be used, although some (HDL) cholesterol are associated with increased experts still recommend less than 130/80 mmHg if cardiovascular risk; high LDL cholesterol can albuminuria is present in patients with chronic usually be treated with available drugs, usually kidney disease.
III. Are there other exceptions to less than140/ V. Hemoglobin/hematocrit 90 mmHg? Most evidence linking the effects on Why are these important? These measurements cardiovascular or renal outcomes to treated blood can identify issues beyond hypertension and car- pressures has been based on clinical trials in middle diovascular disease, including sickle cell anemia aged to elderly patients (typically between 55 and in vulnerable populations and anemia associated 80). Some recent trials suggest that in people aged 80 with chronic kidney disease.
or more, achieving a SBP of less than 150 mmHg is VI. Liver function tests associated with strong cardiovascular and stroke Why are these important? Certain blood pressure protection, and so a target of less than150/90 mmHg drugs can affect liver function, so it is useful to is now recommended for patients in this age group.
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Weber et al.
We have almost no clinical trial evidence about climb stairs, and pursue means of integrating blood pressure targets in patients younger than physical activity into their daily routines.
50; DBP may be important in this age group, so IV. Alcohol consumption: up to two drinks a day can be achieving less than 90 mmHg should be a priority.
helpful in protecting against cardiovascular events, In addition, it is also a reasonable expectation but greater amounts of alcohol can raise blood pres- that targets lower than 140/90 mmHg (e.g., <130/ sure and should therefore be discouraged. In women, 80 mmHg) could be appropriate in young adults, alcohol should be limited to one drink a day.
and can be considered.
V. Cigarette smoking: stopping smoking will not IV. It is important to inform patients that the treatment reduce blood pressure, but as smoking by itself is of hypertension usually is expected to be a life-long such a major cardiovascular risk factor, patients must commitment and that it can be dangerous for them be strongly urged to discontinue this habit. Patients to terminate their treatment with drugs or lifestyle should be warned that stopping smoking may be changes without first consulting their practitioner.
associated with a modest increase in body weight.
12. NONPHARMACOLOGIC TREATMENT 13. DRUG TREATMENT OFHYPERTENSION Several lifestyle interventions have been shown to reduceblood pressure. Apart from contributing to the treatment of I. Starting treatment: (see the algorithm in the .
hypertension, these strategies are beneficial in managing Treatment with drugs should be started in patients most of the other cardiovascular risk factors. In patients with blood pressures at least 140/90 mmHg in whom with hypertension that is no more severe than stage 1 and is lifestyle treatments have not been effective. (Note: as not associated with evidence for abnormal cardiovascular discussed earlier in Section 12 on Nonpharmaco- findings or other cardiovascular risks, 6–12 months of logic treatment, drug treatment can be delayed for lifestyle changes can be attempted in the hope that they some months in patients with stage 1 hypertension may be sufficiently effective to make it unnecessary to use who do not have evidence for abnormal cardiovas- medicines. However, it may be prudent to start treatment cular findings or other risk factors. In settings in with drugs sooner if it is clear that the blood pressure is not which healthcare resources are highly limited, clini- responding to the lifestyle methods or if other risk factors cians can consider extending the nondrug obser- appear. Also, in practice, settings in which patients have vation period in uncomplicated stage 1 hypertensive logistical difficulties in making regular clinic visits, it might patients, provided there is no evidence for an be most practical to start drug therapy early. In general, increase in blood pressure or the appearance of lifestyle changes should be regarded as a complement to cardiovascular or renal findings).
drug therapy rather than an alternative.
In patients with stage 2 hypertension (blood pres-sure 160/100 mmHg), drug treatment should be I. Weight loss: in patients who are overweight or started immediately after diagnosis, usually with a obese, weight loss is helpful in treating hyperten- two-drug combination, without waiting to see the sion, diabetes, and lipid disorders. Substituting fresh effects of lifestyle changes. Drug treatment can also fruits and vegetables for more traditional diets may be started immediately in all hypertensive patients in have benefits beyond weight loss. Unfortunately, whom, for logistical or other practical reasons, the these diets can be relatively expensive and incon- practitioner believes it is necessary to achieve a venient for patients, and can work only if patients more rapid control of blood pressure. The presence are provided with a strong support system. Even of other cardiovascular risk factors should also modest weight loss can be helpful.
accelerate the start of hypertension treatment.
II. Salt reduction: high salt diets are common in many II. For patients aged over 80, the suggested threshold communities. Reduction of salt intake is recom- for starting treatment is at levels of 150/90 mmHg or mended because it can reduce blood pressure above. Thus, the target of treatment will be less than and decrease the need for medications in patients 140/90 mmHg for most patients, but less than 150/ who are ‘salt-sensitive', which may be a fairly com- 90 mmHg for the older patients (unless these mon finding in black communities. Often patients patients have chronic kidney disease or diabetes, are unaware that there is a large amount of salt in when <140/90 mmHg can be considered).
foods such as bread, canned goods, fast foods, III. The treatment regimen: pickles, soups, and processed meats. This intake  Most patients will require more than one drug to can be difficult to change because salty foods are achieve control of their blood pressure.
often part of the traditional diets found in many  In general, increase the dose of drugs, or add new cultures. A related problem is that many people eat drugs, at approximately 2–3-week intervals. This diets that are low in potassium, and they should be frequency can be faster or slower depending on taught about available sources of dietary potassium.
the judgment of the practitioner. In general, the III. Exercise: regular aerobic exercise can help reduce initial doses of drugs chosen should be at least blood pressure, but opportunities to follow a struc- half of the maximum dose so that only one dose tured exercise regimen are often limited. Still, adjustment is required thereafter. It is generally patients should be encouraged to walk, use bicycles, anticipated that most patients should reach an Volume 32
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January 2014 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Blood pressure ≥140/90 in adults aged >18 years (for age ≥80 years, pressure ≥150/90 or ≥140/90 if high risk [diabetes, kidney disease]) Start lifestyle changes (lose weight, reduce dietary salt and alcohol, stop smoking) Start drug therapy (consider a delay in uncomplicated stage 1 patients)* (in all patients) Non-black patients • Kidney disease• Diabetes• Coronary disease • Stroke history • Heart failure [see table of CCB or thiazide ACE-i or ARB CCB or thiazide CCB or thiazide recommended drugs for these conditions] If needed, add .
If needed, add .
If needed, add .
ACE-i or ARB ACE-i or ARB CCB or thiazide ACE-i or ARB combine CCB+thiazide cardiovascular riskfactors or abnormal CCB+thiazide+ACE-i (or ARB) CCB+thiazide+ACE-i (or ARB) findings, some monthsof regularly monitored If needed, add other drugs e.g. spironolactone; centrally acting agents; β-blockers lifestyle managementwithout drugs can be If needed, refer to a hypertension specialist FIGURE 1 Algorithm summarizing the main recommendations of the guidelines. At any stage, it is entirely appropriate to seek help from a hypertension expert if treatmentis proving difficult. In patients with stage 1 hypertension in whom there is no history of cardiovascular, stroke or renal events or evidence of abnormal findings, and whodo not have diabetes or other major risk factors, drug therapy can be delayed for some months. In all other patients (including those with stage 2 hypertension), it isrecommended that drug therapy be started when the diagnosis of hypertension is made. ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptorblocker; CCB, calcium channel blocker; thiazide, thiazide or thiazide-like diuretics. Blood pressure values are mmHg.
effective treatment regimen, whether one, two, or multiple drugs are needed, it is possible to divide three drugs, within 6–8 weeks.
them between the morning and the evening.
 If the untreated blood pressure is at least  The choice of drugs will further be influenced by 20/10 mmHg above the target blood pressure, their availability and affordability. In many cases, consider starting treatment immediately with two it is necessary to use whichever drugs have been provided by government or other agencies. For IV. Choice of drugs: this reason, we will only make recommendations  This should be influenced by the age, ethnicity/ for drug classes, not individual agents, recogniz- race, and other clinical characteristics of the ing that there may be a very limited selection of drugs that can be prescribed by a practitioner.
 The choice of drugs will also be influenced by the Even among generic drugs, there can be a wide other conditions (e.g., diabetes, coronary disease, variation in cost.
etc.) associated with the hypertension (see  Recommendations for drug selection are shown Pregnancy also influences drug choice.
in (Part 1) for patients whose primary  Long-acting drugs that need to be taken only once problem is hypertension, and in (Part 2) daily are preferred to shorter acting drugs that for patients who have a major comorbidity associ- require multiple doses because patients are more ated with their hypertension. The displays likely to follow a simple treatment regimen. For an algorithm that summarizes the use of therapy the same reason, when more than one drug is for most patients with hypertension. The recom- prescribed, the use of a combination product with mendations for particular drug classes are made two appropriate medications in a single tablet can with the recognition that sometimes only alterna- simplify treatment for patients, though these tive drug classes will be available. However, most products can sometimes be more expensive than of the time, the use of any drugs that reduce blood individual drugs. Once-daily drugs can be taken pressure is more likely to help protect patients at any time during the day, most usually either in from strokes and other serious events than giving the morning or in the evening before sleep. If patients no drug at all.
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Weber et al.
TABLE 1. Drug selection in hypertensive patients with or without other major conditions Add second drug if needed If third drug needed to to achieve a BP of (Part 1) Treatment regimens when hypertension is the only or main condition Black patients (African Ancestry): or thiazide diuretic ARBor ACE inhibitor (If Combination of CCB þ ACE unavailable can add alternative inhibitor or ARB þ thiazide first drug choice) White and other non-black CCBor thiazide diuretic Combination of CCB þ ACE patients: aged <60 years inhibitor or ARB þ thiazidediuretic White and other non-black or thiazide diuretic (though ARBor ACE inhibitor (or CCB or Combination of CCB þ ACE patients: aged >60 years ACE inhibitors or ARBs are also thiazide, if ACE inhibitor or ARB inhibitor or ARB þ thiazide usually effective) Add second drug if needed ADD third drug if needed (Part 2) When hypertension is associated with other conditions Hypertension and diabetes ARB or ACE inhibitor Note: in black CCB or thiazide diuretic; Note: in The alternative second drug patients, it is acceptable to start black patients, if starting with (thiazide or CCB) with CCB or thiazide CCB or thiazide, would now addARB or ACE inhibitor Hypertension and chronic kidney ARB or ACE inhibitor Note: in black CCB or thiazide diuretic The alternative second drug patients, good evidence for renal (thiazide or CCB) protective effects of ACEinhibitors Hypertension and clinical b-blocker with ARB or ACE CCB or thiazide diuretic The alternative second step drug coronary artery disease (thiazide or CCB) Hypertension and stroke history ACE inhibitor or ARB Thiazide diuretic or CCB The alternative second drug (CCB Hypertension and heart failure Patients with symptomatic heart failure should usually receive an ARB or ACE inhibitor þ b-blocker þ diuretic þ spironolactone regardless of blood pressure. Dihydropyridine CCB can be added if needed for BP control.
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; CCB, calcium channel blocker; eGFR, estimated glomerular filtration rate.
aCCBs generally preferred, but thiazides may cost less.
bARBs can be considered because ACE inhibitors can cause cough and angioedema, though ACE inhibitors may cost less.
cIf eGFR less than 40 ml/min, a loop diuretic, for example, furosemide or torsemide, may be needed.
dIf previous myocardial infarction, a b-blocker and ARB/or ACE inhibitor are indicated regardless of blood pressure.
eIf using a diuretic, there is good evidence for indapamide (if available).
14. BRIEF COMMENTS ON DRUG harmful. An even greater increase in creatininesometimes occurs when ACE inhibitors are combined with diuretics and produce large blood pressure Note: There is an assumption, unless otherwise stated, that reductions. Again, this change is reversible, though all drugs in a class are similar to each other. We only it may be necessary to reduce doses of one or both mention individual agents if they have an important pro- drugs. If creatinine levels increase substantially, this perty that is not shared by the others in its class. can be due to concomitant treatment with NSAIDs, or provides a list of commonly used antihypertensive drugs it may indicate the presence of renal artery stenosis.
and their doses.

The side-effects with ACE inhibitors are generally not dose-dependent; they occur as frequently at low Angiotensin-converting enzyme inhibitors doses as at high doses. Thus, it can be perfectly
These agents reduce blood pressure by blocking the acceptable when using these agents to start at medium renin–angiotensin system. They do this by preventing or even high doses. The one exception to this rule is conversion of angiotensin I to the blood pressure- hyperkalemia, which may occur more frequently at raising hormone angiotensin II. They also increase higher ACE inhibitor doses.
availability of the vasodilator, bradykinin, by blocking
These drugs have established clinical outcome its breakdown.
benefits in patients with heart failure, post-myocardial
ACE inhibitors are well tolerated. Their main side- infarction, left ventricular systolic dysfunction, and effect is cough (most common in women and in patients with diabetic and nondiabetic chronic kidney patients of Asian and African background). Angioe- dema is an uncommon but potentially serious com-
In general, the ACE inhibitors are more effective as plication that can threaten airway function; it occurs monotherapy in reducing blood pressure in white most frequently in black patients.
patients than in blacks, possibly because the renin–
These drugs can increase serum creatinine by as much angiotensin system is often less active in black as 30%, but this is usually because they reduce pres- patients. However, these drugs are equally effective sure within the renal glomerulus and decrease filtra- in reducing blood pressure in all ethnic and racial tion; this is a reversible change in function and is not groups when combined with either CCBs or diuretics.
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TABLE 2. Doses of commonly used antihypertensive drugs TABLE 2 (Continued) Calcium channel blockers Central a-agonists 0.1–0.2 twice daily TTS-1, once weekly TTS-1, 2 or 3, once weekly 250–500 twice daily Adrenergic depleters 5–10 twice daily
Do not combine ACE inhibitors with ARBs; each of Drugs that target the renin–angiotensin system Angiotensin-converting enzyme inhibitors (ACEIs) these drug types is beneficial in patients with kidney disease, but in combination they may actually have 50–100 twice daily adverse effects on kidney function.

When starting treatment with an ACE inhibitor, there is a risk of hypotension in patients who are already taking diuretics or are on very low salt diets or are dehydrated (e.g., laborers in hot climates, patients with diarrhea). For patients taking a diuretic, skipping a dose before starting the ACE inhibitor helps prevent Angiotensin receptor blockers (ARBs) this sudden effect on blood pressure.

ACE inhibitors must not be used in pregnancy, especially in the second or third trimesters, as they can compromise the normal development of the Angiotensin receptor blockers Direct renin inhibitor
These drugs, like the ACE inhibitors, antagonize the renin–angiotensin system. They reduce blood pres- Thiazide and thiazide-like diuretics sure by blocking the action of angiotensin II on its AT1 receptor and thus preventing the vasoconstrictor effects of this receptor.

The ARBs are well tolerated. As they do not cause cough and only rarely cause angioedema, and have effects and benefits similar to ACE inhibitors, they are generally preferred over the ACE inhibitors if they are available and affordable. Like the ACE inhibitors, the ARBs can increase serum creatinine (see comments about ACE inhibitors), but usually this is a functional change that is reversible and not harmful.

These drugs do not appear to have dose-dependent side-effects, so it is perfectly reasonable to start treat- ment with medium or even maximum approved
These drugs have the same benefits on cardiovascular 3.125 twice daily 6.25–25 twice daily 100–300 twice daily and renal outcomes as the ACE inhibitors.
Metoprolol succinate
Like the ACE inhibitors, they tend to work better in Metoprolol tartrate 50–100 twice daily White and Asian patients than Black, but when com- bined with either CCBs or diuretics, they become equally effective in all patient groups.
40–160 twice daily
Do not combine ARBs with ACE inhibitors; each of a-Adrenergic receptor blockers these drug types is beneficial in patients with kidney 1–5 twice daily disease, but in combination they may actually have adverse effects on renal events.
Vasodilators, central a-agonists, and adrenergic depleters
When starting treatment with an ARB in patients already on diuretics, it may be beneficial to skip a 25–100 twice daily dose of the diuretic to prevent a very sudden fall inblood pressure.
Journal of Hypertension Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Weber et al.

ARBs must not be used in pregnancy, especially in the
Because the nondihydropyridine drugs, verapamil second or third trimesters, as they can compromise the and diltiazem, can slow the heart rate, they can some- normal development of the fetus.
times be preferred in patients with fast heart rates andeven for rate control in patients with atrial fibrillationwho cannot tolerate b-blockers. The nondihydro- Thiazide and thiazide-like diuretics pyridine drugs can also reduce proteinuria.

These agents work by increasing excretion of sodium
The CCBs have powerful blood pressure-reducing by the kidneys and additionally may have some effects, particularly when combined with ACE inhibi- tors or ARBs. They are equally effective in all racial
Clinical outcome benefits (reduction of strokes and and ethnic groups.
major cardiovascular events) have been best estab-
The dihydropyridine, but not the nondihydropyri- lished with chlorthalidone, indapamide, and hydro- dine, CCBs can be safely combined with b-blockers.
chlorothiazide, though the evidence for the first two ofthese agents has been the strongest.

Chlorthalidone has more powerful effects on blood pressure than hydrochlorothiazide (when the same
The b-blockers reduce cardiac output and also doses are compared) and has a longer duration of decrease the release of renin from the kidney.

They have strong clinical outcome benefits in patients
The main side-effects of these drugs are metabolic with histories of myocardial infarction and heart fail- (hypokalemia, hyperglycemia, and hyperuricemia).
ure and are efficacious in the management of angina The likelihood of these problems can be reduced by using low doses (e.g., 12.5 or 25 mg of hydro-
They are less effective in reducing blood pressure in chlorothiazide or chlorthalidone) or by combining black patients than in patients of other ethnicities.
these diuretics with ACE inhibitors or ARBs, which
The b-blockers may not be as effective as the other have been shown to reduce these metabolic changes.
major drug classes in preventing stroke or cardiovas- Combining diuretics with potassium-sparing agents cular events in hypertensive patients, but are drugs of also helps prevent hypokalemia.
choice in patients with histories of myocardial infarc-
The diuretics are most effective in reducing blood tion or heart failure.
pressure when combined with ACE inhibitors or
Many of these agents have adverse effects on glucose ARBs, although they are also effective when com- metabolism and, therefore, are not recommended in bined with CCBs.
patients at risk of becoming diabetic, especially incombination with diuretics. They may also be associ- Note: thiazides and b-blockers are also an effective ated with heart block in susceptible patients.
combination for reducing blood pressure, but as both
The main side-effects with b-blockers are reduced classes can increase blood glucose concentrations this sexual function, fatigue, and reduced exercise toler- combination should be used with caution in patients at risk of developing diabetes.

The combined a-blocker and b-blocker, labetalol, is widely used intravenously for hypertensive emergen- Calcium channel blockers cies, and is also used orally for treating hypertension
These agents reduce blood pressure by blocking the in pregnancy and in breastfeeding mothers.
inward flow of calcium ions through the L channels ofarterial smooth muscle cells.

There are two main types of CCBs: dihydropyri- dines such as amlodipine and nifedipine, which
The a-blockers reduce blood pressure by blocking work by dilating arteries; and nondihydropyridines arterial a-adrenergic receptors and thus preventing such as diltiazem and verapamil, which dilate the vasoconstrictor actions of these receptors.
arteries somewhat less but also reduce heart rate
These drugs are less widely used as first step drugs and contractility.
than other classes because clinical outcome benefits
Most experience with these agents has been with the have not been as well established as with other dihydropyridines such as amlodipine and nifedipine, agents. However, they can be useful in treating which have been shown to have beneficial effects on resistant hypertension when used in combination cardiovascular and stroke outcomes in hypertension with agents such as diuretics, b-blockers, and ACE
The main side-effect of CCBs is peripheral edema,
To be maximally effective, they should usually be which is most prominent at high doses; this finding combined with a diuretic. As the a-blockers can have can often be attenuated by combining these agents somewhat beneficial effects on blood glucose and with ACE inhibitors or ARBs.
lipid levels, they can potentially neutralize some of
The nondihydropyridine CCBs are not recommended the adverse metabolic effects of the diuretics.
in patients with heart failure, but amlodipine appears
The a-blockers are effective in treating benign pro- to be safe when given to heart failure patients receiv- static hypertrophy, and so can be a valuable part of ing standard therapy (including ACE inhibitors) for hypertension treatment regimens in older men who this condition.
have this condition.
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January 2014 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Centrally acting agents potassium levels must be monitored within the first
These drugs, the most well known of which are month of treatment and then on a regular basis (every clonidine and a-methyldopa, work primarily by 3–6 months).
reducing sympathetic outflow from the central ner-vous system.
15. TREATMENT-RESISTANT
They are effective at reducing blood pressure in most patient groups.

Bothersome side-effects such as drowsiness and dry
Hypertension can be controlled (blood pressure mouth have reduced their popularity. Treatment with <140/90 mmHg in most patients) by using either a clonidine skin patch causes fewer side-effects than one, two, or three drugs as described earlier (ACE the oral agent, but the patch is not always available inhibitor or ARB/CCB/diuretic) in full or maximally and can be more costly than the tablets.
tolerated doses. The most widely used two-drug com-
In certain countries, including the United States, bination, ACE inhibitors either with CCBs or diuretics, a-methyldopa is widely employed for treating hyper- or angiotensin receptor blockers either with CCBs or tension in pregnancy.
diuretics, can control blood pressure in about 80%of patients.
Direct vasodilators
Confirm that the blood pressure is truly uncontrolled
Because these agents, specifically hydralazine and by checking home pressures, or if available, by using minoxidil, often cause fluid retention and tachycardia, ambulatory blood pressure monitoring.
they are most effective in reducing blood pressure
For patients not controlled on three drugs, adding when combined with diuretics and b-blockers or a mineralocorticoid antagonist like spironolactone, a sympatholytic agents. For this reason, they are now b-blocker, a centrally acting agent, an a-blocker, or a usually used only as fourth-line or later additions to direct vasodilator will often be helpful.
treatment regimens.

If blood pressure is still not controlled, it is important
Hydralazine is the more widely used of these agents.
to make certain that patients are actually taking their The powerful drug minoxidil is sometimes used by medicines. Question their families, check their pre- specialists in patients whose blood pressures are scriptions, and ask questions about side-effects to difficult to control. Fluid retention and tachycardia help confirm compliance with treatment.
are frequent problems with minoxidil, as well as
Check whether patients are taking other medicines unwanted hair growth (particularly in women). Furo- that can interfere with their hypertension treatment, semide is often required to cope with the fluid reten- for example, NSAIDs, cold remedies, and some anti- depressants. Also ask about diet: blood pressures insome patients are especially sensitive to such factorsas excessive salt intake.
Mineralocorticoid receptor antagonists
Consider secondary causes of hypertension if all these
The best known of these agents is spironolactone.
more simple approaches are unsuccessful.
Although it was originally developed for the treatment  Secondary hypertension can be suggested by the of high aldosterone states, it recently has become part sudden onset of hypertension, or by the loss of of the standard treatment for heart failure. Eplerenone blood pressure control in patients previously well is a newer and better tolerated agent, although most managed or by the occurrence of a hypertension experience in difficult-to-control hypertension has been with spironolactone.
 Chronic kidney disease: this common secondary
In addition, these agents can be very effective in cause of hypertension should normally be revealed reducing blood pressure when added to standard by the initial patient evaluation (laboratory tests of three-drug regimens (ACE inhibitor or ARB/CCB/diu- creatinine, etc.). These patients, if possible, should retic) in treatment-resistant patients. This may be be referred to a nephrologist.
because aldosterone excess can contribute to resistant  Aldosterone excess: this is suggested by hypokale- mia during the initial evaluation, though this con-
Symptomatic side-effects of gynecomastia (swelling dition can occur even when potassium levels and tenderness of breasts in both men and women) appear normal. About 20% of patients whose blood and sexual dysfunction are common. These can be pressures remain high despite taking three drugs minimized by using spironolactone in a low dose (no have evidence for aldosterone excess. Confirming more than 25 mg daily) or by using the more selective this diagnosis usually requires assistance from (but more expensive) agent, eplerenone. Hyperkale- clinical hypertension specialists.
mia can also become a problem with these agents,  Sleep apnea: this is common in obese people. Not particularly when added to ACE inhibitors or ARBs in all patients with sleep apnea have hypertension, patients with reduced renal function. These agents but there is a clear association. A preliminary diag- should be used with caution when the eGFR is below nosis can be made by finding a history of snoring 50. In particular, when mineralocorticoid receptor during sleep and daytime tiredness. A definitive blockers are combined with ACE inhibitors or ARBs, diagnosis usually requires a sleep laboratory study.
Journal of Hypertension Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Weber et al.
 Other secondary causes of hypertension such as VSR: Consultant: Medtronic, Daiichi-Sankyo, Forest.
renal artery stenosis or coarctation of the aorta DLC: No conflicts of interest.
usually require evaluation by a specialist.
JCC: No conflicts of interest.
RRJC: No conflicts of interest.
ST: No conflicts of interest.
The authors of this statement acknowledge that there are DK: Research Funding: Medtronic.
insufficient published data from clinical trials in hyper- RT: Research Funding: NIH. Consultant: Medtronic, Jans- tension to create recommendations that are completely sen, Merck, GSK.
evidence-based, and so inevitably some of our recommen- JC: Research Funding and Speaker: Servier in relation to dations reflect expert opinion and experience.
ADVANCE trial and Post-trial study.
We also should point out that because of the major AJR: No conflicts of interest.
differences in resources among points of care, it is not GLB: Research Funding: Takeda. Consultant: Takeda, possible to create a uniform set of guidelines. For this reason, we have written a broad statement on the manage- Relypsa, Janssen, BMS.
ment of hypertension and have not presumed to anticipate JW: Consultant and Speaker: Boehringer-Ingelheim, the conditions or shortfalls that might exist in particular MSD, Novartis, Omron, Pfizer, Servier and Takeda.
communities. We expect that experts who are familiar with AES: No conflicts of interest.
local circumstances will feel free to use their own judgment JDB: Research and Consultant: CVRx.
in modifying our recommendations and to create practical RMT: No conflicts of interest.
instructions to help guide front-line practitioners in provid- DS: Research: Medtronic, CVRx. Consultant: Takeda, ing the best care possible.
UCB, Novartis, Medtronic, CVRx. Speaker: Takeda.
SBH: Speaker: Novartis, Servier.
A note to colleaguesThe authors of this statement would welcome comments Suggested Reading and suggestions from colleagues. We recognize that in this 1. Chobanian AV, Bakris GL, Black HR, Cushman WC, initial version of the guidelines, there will probably be Green LA, Izzo JL Jr, et al., National High Blood omissions, redundancies, and inaccuracies. Please feel free Pressure Education Program Coordinating Commit- to get in touch with us either by letters to the Journal or by tee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treat-ment of High Blood Pressure. Hypertension 2003; 2. Flack JM, Sica DA, Bakris G, Brown AL, Ferdinand This statement was written under the sponsorship of the KC, Grimm RH Jr, et al., International Society on American Society of Hypertension and the International Hypertension in Blacks. Management of high blood Society of Hypertension. In addition, the Asia Pacific pressure in blacks: an update of the International Society of Hypertension has endorsed these guidelines.
Society on Hypertension in Blacks consensus state- The statement was prepared without any external fund- ment. Hypertension 2010; 56:780–800.
ing. The work and time of the authors was provided by 3. National Institute for Healthcare Evidence. CG127 them entirely on a volunteer basis.
Hypertension: clinical management of primaryhypertension in adults. On-line: NICE Clinical Guide- Conflicts of interest lines. August 2001.
MAW: Research funding: Medtronics. Consulting: Boeh- 4. Mancia G, Fagard R, Narkiewicz K, Redo´n J, ringer-Ingelheim, Novartis, Astra Zeneca, Takeda, Forest.
¨hm M, et al., Task Force Members.
Speaker: Daiichi Sankyo, Takeda, Forest.
2013 ESH/ESC Guidelines for the management of ELS: Research Funding: Canadian Institutes of Health arterial hypertension: the Task Force for the man- Research, Canada Research Chairs program of CIHR/Gov- agement of arterial hypertension of the European ernment of Canada, Servier France. Consultant: Servier, Society of Hypertension (ESH) and of the European Novartis. Speaker Bureau: Forest Canada, Pfizer Japan.
Society of Cardiology (ESC). J Hypertens 2013; 31: WBW: Research Funding: National Institutes of Health.
Consulting: Safety Committees (DSMB, CEC, Steering Com- 5. Lewington S, Clarke R, Qizilbash N, Peto R, Collins mittees); Ardea Biosciences, Inc.; AstraZeneca; Dendreon, R, Prospective Studies Collaboration. Age-specific Forest Research Institute, Inc.; Roche; St. Jude's Medical, relevance of usual blood pressure to vascular Takeda Global Research, Teva Neuroscience.
mortality: a meta-analysis of individual data for SM: No conflicts of interest.
one million adults in 61 prospective studies. Lancet LHL: No conflicts of interest.
JGK: No conflicts of interest.
6. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray JMF: Research Funding: Novartis, Medtronic. Consultant: GA, Harsha D, et al., DASH-Sodium Collaborative Novartis, Medtronic, Back Beat Hypertension.
Research Group. Effects on blood pressure of BLC: Research Funding: NIH and VA.
reduced dietary sodium and the Dietary Approaches BJM: No conflicts of interest.
to Stop Hypertension (DASH) diet. DASH-Sodium Volume 32
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