Among individuals with hypertension, self-monitoring of BP, without other interventions, has shown limited evidence for treatment-related BP reduction and achievement of BP However, with the increased recogni- tion of inconsistencies between office and out-of-office BPs (see Section 4.4) and greater reduction in BP being recom- mended for hypertension control, increased attention is being paid to out-of-office BP readings. Although ABPM is generally accepted as the best out-of-office measurement method, HBPM is often a more practical approach in clini- cal practice. Recommended procedures for the collection of HBPM data are provided in Table 10. If self-monitor- ing is used, it is important to ensure that the BP measure- ment device used has been validated with an internationally accepted protocol and the results have been published in a peer-reviewed journal.S4.2-7 A guide to the relationship between HBPM BP readings and corresponding read- ings obtained in the office and by ABPM is presented in Table 11. The precise relationships between office readings, ABPM, and HBPM are unsettled, but there is general agree- ment that office BPs are often higher than ABPM or HBPM BPs, especially at higher BPs. Recommendation-Specific Supportive Text 1. ABPM is used to obtain out-of-office BP readings at set intervals, usually over a period of 24 hours. HBPM is used to obtain a record of out-of-office BP readings taken by a patient. Both ABPM and HBPM typically provide BP estimates that are based on multiple mea- surements. A systematic review conducted by the US Preventive Services Task Force reported that ABPM provided a better method to predict long-term CVD out- comes than did office BPs. It incorporates new informa- tion from studies of HBPM, ABPM, the relationship of overall CVD risk to the effectiveness of blood pressure lowering, clinical outcomes related to different blood pressure goals, strategies to improve blood pressure con- trol and various other areas. A small body of evidence suggested, but did not confirm, that HBPM could serve as a similar predictor of outcomes.S4.2-4 Meta-analyses of RCTs have identified clinically useful reductions in SBP and DBP and achievement of BP goals at 6 months and 1 year when self-monitoring of BP has been used in con- junction with other interventions, compared with usual care. Meta-analyses of RCTs have identified only small Table 9. Selection Criteria for BP Cuff Size for Measurement of BP in Adults Arm Circumference Usual Cuff Size 22 26 cm Small adult 27 34 cm Adult 35 44 cm Large adult 45 52 cm Adult thigh Adapted with permission from Pickering et alS4.1-2 (American Heart Association, Inc.). BP indicates blood pressure. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e25 net reductions in SBP and DBP at 6 months and 1 year for use of self-monitoring of BP on its own, as compared with usual care.S4.2-1,S4.2-5,S4.2-6 See Section 4.4 for addi- tional details of diagnostic classification and Section 12 for additional details of telehealth and out-of-office BP measurement for management of high BP. 4.3. Ambulatory BP Monitoring All of the major RCTs have been based on use of clinic BP readings. However, ABPM is often used to supplement BP readings obtained in office settings.S4.3-1 The monitors are usually programmed to obtain readings every 15 to 30 min- utes throughout the day and every 15 minutes to 1 hour during the night. ABPM is conducted while individuals go about their normal daily activities. ABPM can a) provide estimates of mean BP over the entire monitoring period and separately during nighttime and daytime, b) determine the daytime-to-nighttime BP ratio to identify the extent of nocturnal dipping, c) identify the early-morning BP surge pattern, d) estimate BP variability, and e) allow for recog- nition of symptomatic hypotension. The US Centers for Medicaid & Medicare Services and other agencies provide reimbursement for ABPM in patients with suspected white Medicare claims for ABPM between 2007 and 2010 were reimbursed at a median of $52 and were submitted for <1% of beneficiaries.S4.3-3,S4.3-4 A list of devices validated for ABPM is available.S4.3-5,S4.3-6 ABPM and HBPM definitions of high BP use different BP thresholds than those used by the previously mentioned office- based approach to categorize high BP identified in Section 3.1. Table 11 provides best estimates for corresponding home, daytime, nighttime, and 24-hour ambulatory levels of BP, including the values recommended for identification of hypertension with office measurements. Typically, a clinic BP of 140/90 mm Hg corresponds to home BP values of 135/85 mm Hg and toABPM values defined as a daytime SBP/DBP of 135/85 mm Hg, a nighttime SBP/DBP of 120/70 mm Hg, and These thresh- olds are based on data from European, Australian, and Asian populations, with few data available for establishing appropri- ate thresholds for US populations.S4.3-9 S4.3-13 They are provided as a guide but should be interpreted with caution. Higher day- time SBP measurements from ABPM can be associated with an increased risk of CVD and all-cause death independent of clinic-measured BP.S4.3-14 A meta-analysis of observational studies that included 13844 individuals suggested nighttime BP is a stronger risk factor for CHD and stroke than either clinic or daytime BP.S4.3-15 Methodological issues complicate the interpretation of data from studies that report office and out-of-office BP read- ings. Definitions and diagnostic methods for identifying white coat hypertension and masked hypertension (see Section 4.4) have not been standardized. The available studies have dif- fered with regard to number of office readings obtained, use of 24-hour ABPM, use of daytime-only ABPM, inclusion of day- time and nighttime BP readings as separate categories, HBPM Table 11. Corresponding Values of SBP/DBP for Clinic, HBPM, Daytime, Nighttime, and 24-Hour ABPM Measurements Clinic HBPM Daytime ABPM Nighttime ABPM ABPM ABPM indicates ambulatory blood pressure monitoring; BP, blood pressure; DBP, diastolic blood pressure; HBPM, home blood pressure monitoring; and SBP, systolic blood pressure. Table 10. Procedures for Use of HBPMS4.2 5 S4.2 7 Patient training should occur under medical supervision, including: Information about hypertension Selection of equipment Acknowledgment that individual BP readings may vary substantially Interpretation of results Devices: Verify use of automated validated devices. Use of auscultatory devices (mercury, aneroid, or other) is not generally useful for HBPM because patients rarely master the technique required for measurement of BP with auscultatory devices. Monitors with provision for storage of readings in memory are preferred. Verify use of appropriate cuff size to fit the arm (Table 9). Verify that left/right inter-arm differences are insignificant. If differences are significant, instruct patient to measure BPs in the arm with higher readings. Instructions on HBPM procedures: Remain still: Avoid smoking, caffeinated beverages, or exercise within 30 min before BP measurements. Ensure 5 min of quiet rest before BP measurements. Sit correctly: Sit with back straight and supported (on a straight-backed dining chair, for example, rather than a sofa). Sit with feet flat on the floor and legs uncrossed. Keep arm supported on a flat surface (such as a table), with the upper arm at heart level. Bottom of the cuff should be placed directly above the antecubital fossa (bend of the elbow). Take multiple readings: Take at least 2 readings 1 min apart in morning before taking medications and in evening before supper. Optimally, measure and record BP daily. Ideally, obtain weekly BP readings beginning 2 weeks after a change in the treatment regimen and during the week before a clinic visit. Record all readings accurately: Monitors with built-in memory should be brought to all clinic appointments. BP should be based on an average of readings on 2 occasions for clinical decision making. The information above may be reinforced with videos available online. See Table 11 for HBPM targets. BP indicates blood pressure; and HBPM, home blood pressure monitoring. for monitoring out-of-office BP levels, and even the BP thresh- olds used to define hypertension with ABPM or HBPM read- ings. In addition, there are few data that address reproducibility of these hypertension profiles over time, with several studies suggesting progression of white coat hypertension and espe- cially of masked hypertension to sustained office-measured 4.4. Masked and White Coat Hypertension Recommendations for Masked and White Coat Hypertension References that support recommendations are summarized in Online Data Supplements 4, 5, and 6. COR LOE Recommendations IIa B-NR 1. In adults with an untreated SBP greater than 130 mm Hg but less than 160 mm Hg or DBP greater than 80 mm Hg but less than 100 mm Hg, it is reasonable to screen for the presence of white coat hypertension by using either daytime ABPM or HBPM before diagnosis of hypertension.S4.4-1 S4.4-8 IIa C-LD 2. In adults with white coat hypertension, periodic monitoring with either ABPM or HBPM is reasonable to detect transition to sustained hypertension (S4.4-2,S4.4- 5,S4.4-7). IIa C-LD 3. In adults being treated for hypertension with office BP readings not at goal and HBPM readings suggestive of a significant white coat effect, confirmation by ABPM can be useful (S4.4-9,S4.4-10). IIa B-NR 4. In adults with untreated office BPs that are consistently between 120 mm Hg and 129 mm Hg for SBP or between 75 mm Hg and 79 mm Hg for DBP, screening for masked hypertension with HBPM (or ABPM) is 8,S4.4-11). IIb C-LD 5. In adults on multiple-drug therapies for hypertension and office BPs within 10 mm Hg above goal, it may be reasonable to screen for white coat effect with HBPM (or ABPM) (S4.4-3,S4.4-7,S4.4-12). IIb C-EO 6. It may be reasonable to screen for masked uncontrolled hypertension with HBPM in adults being treated for hypertension and office readings at goal, in the presence of target organ damage or increased overall CVD risk. IIb C-EO 7. In adults being treated for hypertension with elevated HBPM readings suggestive of masked uncontrolled hypertension, confirmation of the diagnosis by ABPM might be reasonable before intensification of antihypertensive drug treatment. Synopsis The availability of noninvasive BP monitoring techniques has resulted in differentiation of hypertension into several clinically useful categories that are based on the place of BP measurement (Table 12).S4.4-1,S4.4-13,S4.4-14 These include masked hypertension and white coat hypertension, in addition to sus- tained hypertension. White coat hypertension is characterized by elevated office BP but normal readings when measured outside the office with either ABPM or HBPM. In contrast, masked hypertension is characterized by office readings sug- gesting normal BP but out-of-office (ABPM/HBPM) read- ings that are consistently above normal.S4.4-15 In sustained hypertension, BP readings are elevated in both office and out- of-office settings. In patients treated for hypertension, both white coat effect (higher office BPs than out-of-office BPs) and masked uncontrolled hypertension (controlled office BPs but uncontrolled BPs in out-of-office settings) categories have been reported.S4.4-5,S4.4-15,S4.4-16 The white coat effect (usu- ally considered clinically significant when office SBP/DBPs are >20/10 mm Hg higher than home or ABPM SBP/DBPs) has been implicated in pseudo-resistant hypertension (see Section 11.1) and results in an underestimation of office BP The prevalence of masked hyperten- sion varies from 10% to 26% (mean 13%) in population- based surveys and from 14% to 30% in normotensive clinic The risk of CVD and all-cause mortality in persons with masked hypertension is similar to that noted in those with sus- tained hypertension and about twice as high as the correspond- ing risk in their normotensive counterparts.S4.4-3,S4.4-4,S4.4-6,S4.4-8,S4.4-11 The prevalence of masked hypertension increases with higher office BP readings.S4.4-20,S4.4-22,S4.4-23 The prevalence of white coat hypertension is higher with female versus male sex, nonsmoking ver- sus current smoking status, and routine office measurement of BP by clinician observers versus unattended BP measure- ments. Many, but not all, studiesS4.4-4,S4.4-6,S4.4-8,S4.4-25,S4.4-26 have identified a minimal increase in risk of CVD complications or all-cause mortality in patients who have white coat hyperten- sion. This has resulted in a recommendation by some panels to screen for white coat hypertension with ABPM (or HBPM) to avoid initiating antihypertensive drug treatment in such The white coat effect and masked uncontrolled hypertension appear to follow the risk profiles of their white coat hypertension and masked hypertension coun- There are no data on the risks and benefits of treating white coat and masked hypertension. Despite these method- ological differences, the data are consistent in indicating that Table 12. BP Patterns Based on Office and Out-of-Office Measurements Office/Clinic/ Healthcare Setting Home/Nonhealthcare/ ABPM Setting Normotensive No hypertension No hypertension Sustained hypertension Hypertension Hypertension Masked hypertension No hypertension Hypertension White coat hypertension Hypertension No hypertension ABPM indicates ambulatory blood pressure monitoring; and BP, blood pressure. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e27 masked hypertension and masked uncontrolled hypertension are associated with an increased prevalence of target organ damage and risk of CVD, stroke, and mortality compared with normotensive individuals and those with white coat hypertension. Figure 1 is an algorithm on the detection of white coat hypertension or masked hypertension in patients not on drug therapy. Figure 2 is an algorithm on detection of white coat effect or masked uncontrolled hypertension in patients on drug therapy. Table 12 is a summary of BP patterns based on office and out-of-office measurements. Recommendation-Specific Supportive Text 1. White coat hypertension prevalence averages approxi- mately 13% and as high as 35% in some hypertensive and ABPM and HBPM are better predictors of CVD risk due to elevated BP than are of- fice BP measurements, with ABPM being the preferred measurement option. The major clinical relevance of white coat hypertension is that it has typically been as- sociated with a minimal to only slightly increased risk of CVD and all-cause mortality risk.S4.4-3,S4.4-4,S4.4-7,S4.4-11,S4.4-24 If ABPM resources are not readily available, HBPM pro- vides a reasonable but less desirable alternative to screen for white coat hypertension, although the overlap with ABPM is only 60% to 70% for detection of white coat 2. The incidence of white coat hypertension converting to sustained hypertension (justifying the addition of antihy- pertensive drug therapy to lifestyle modification) is 1% to 5% per year byABPM or HBPM, with a higher incidence of conversion in those with elevated BP, older age, obe- sity, or black race.S4.4-2,S4.4-7 3. The overlap between HBPM and both daytime and 24-hour ABPM in diagnosing white coat hyperten- sion is only 60% to 70%, and the data for prediction of CVD risk are stronger with ABPM than with office Because a diagnosis of white coat hypertension may result in a decision not to treat or intensify treatment in patients with elevated office BP readings, confirmation of BP control by ABPM in ad- dition to HBPM provides added support for this decision. 4. In contrast to white coat hypertension, masked hyperten- sion is associated with a CVD and all-cause mortality risk twice as high as that seen in normotensive individuals, with a risk range similar to that of patients with sustained Therefore, out- of-office readings are reasonable to confirm BP control seen with office readings. 5. The white coat effect has been implicated in office- measured uncontrolled hypertension and pseudo- resistant hypertension, which may result in BP control being underestimated when subsequently assessed by The risk of vascular complications in patients with office-measured uncontrolled hyperten- sion with a white coat effect is similar to the risk in those with controlled hypertension.S4.4-3,S4.4-4,S4.4-7,S4.4-11,S4.4-12 White coat hypertension and white coat effect raise the concern that unnecessary antihypertensive drug therapy may be initiated or intensified. Because a diagnosis of white coat hypertension or white coat effect would result in a deci- sion to not treat elevated office BP readings, confirmation of BP control by HBPM (or ABPM) provides more de- finitive support for the decision not to initiate antihyper- tensive drug therapy or accelerate treatment. 6. Analogous to masked hypertension in untreated patients, masked uncontrolled hypertension is defined in treated pa- tients with hypertension by office readings suggesting ad- equate BP control but out-of-office readings (HBPM) that remain consistently above goal.S4.4-3,S4.4-15,S4.4-16,S4.4-32,S4.4-33 The CVD risk profile for masked uncontrolled hyper- tension appears to follow the risk profile for masked Although the evidence is consistent in identifying the increased risk of masked uncontrolled hypertension, evidence is lacking on whether the treatment of masked hypertension or masked uncontrolled hypertension reduces clinical outcomes. A suggestion for assessing CVD risk is pro- vided in Section 8. 7. Although both ABPM and HBPM are better predictors of CVD risk than are office BP readings, ABPM confir- mation of elevated BP by HBPM might be reasonable because of the more extensive documentation of CVD risk with ABPM. However, unlike the documentation of a significant white coat effect to justify the decision to not treat an elevated clinic BP, it is not mandatory to confirm masked uncontrolled hypertension determined by HBPM. Figure 1. Detection of white coat hypertension or masked hypertension in patients not on drug therapy. Colors correspond to Class of Recommendation in Table 1. ABPM indicates ambulatory blood pressure monitoring; BP, blood pressure; and HBPM, home blood pressure monitoring. 5. Causes of Hypertension 5.1. Genetic Predisposition Hypertension is a complex polygenic disorder in which many genes or gene combinations influence BP.S5.1-1,S5.1-2 Although several monogenic forms of hypertension have been identified, such as glucocorticoid-remediable aldosteronism, Liddle s syndrome, Gordon s syndrome, and others in which single- gene mutations fully explain the pathophysiology of hyper- tension, these disorders are rare.S5.1-3 The current tabulation of known genetic variants contributing to BP and hypertension includes more than 25 rare mutations and 120 single-nucleo- However, even with the discov- ery of multiple single-nucleotide polymorphisms influencing control of BP since completion of the Human Genome Project in 2003, the associated variants have only small effects. Indeed, at present, the collective effect of all BP loci identified through genome-wide association studies accounts for only about 3.5% of BP variability.S5.1-4 The presence of a high num- ber of small-effect alleles associated with higher BP results in a more rapid increase in BP with age.S5.1-5 Future studies will need to better elucidate genetic expression, epigenetic effects, transcriptomics, and proteomics that link genotypes with underlying pathophysiological mechanisms. 5.2. Environmental Risk Factors Various environmental exposures, including components of diet, physical activity, and alcohol consumption, influence BP. Many dietary components have been associated with Some of the diet-related factors associated with high BP include overweight and obesity, excess intake of sodium, and insufficient intake of potassium, calcium, magnesium, protein (especially from vegetables), fiber, and fish fats. Poor diet, physical inactivity, and excess intake of alcohol, alone or in combination, are the underlying cause of a large proportion of hypertension. Gut microbiota have also been linked to hypertension, especially in experimental Some of the best-proven environmental rela- tionships with high BP are briefly reviewed below, and non- pharmacological interventions to lower BP are discussed in Section 6.2. 5.2.1. Overweight and Obesity Insurance industry actuarial reports have identified a strik- ing relationship between body weight and high BPS5.2.1-1 and a direct relationship between overweight/obesity and Epidemiological studies, including the Framingham Heart StudyS5.2.1-3 and the Nurses Health have consistently identified a direct relation- ship between body mass index and BP that is continuous and almost linear, with no evidence of a threshold.S5.2.1-5,S5.2.1-6 The relationship with BP is even stronger for waist-to- hip ratio and computed tomographic measures of central Attributable risk estimates from the Nurses Health Study suggest that obesity may be respon- sible for about 40% of hypertension, and in the Framingham Offspring Study, the corresponding estimates were even Figure 2. Detection of white coat effect or masked uncontrolled hypertension in patients on drug therapy. Colors correspond to Class of Recommendation in Table 1. See Section 8 for treatment options. ABPM indicates ambulatory blood pressure monitoring; BP, blood pressure; CVD, cardiovascular disease; and HBPM, home blood pressure monitoring. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e29 higher (78% in men and 65% in women).S5.2.1-8,S5.2.1-9 The relationship between obesity at a young age and change in obesity status over time is strongly related to future risk of hypertension. In combined data from 4 longitudinal stud- ies begun in adolescence with repeat examination in young adulthood to early middle age, being obese continuously or acquiring obesity was associated with a relative risk of 2.7 for developing hypertension. Becoming normal weight reduced the risk of developing hypertension to a level similar to those who had never been obese.S5.2.1-10 5.2.2. Sodium Intake Sodium intake is positively associated with BP in migrant,S5.2.2-11 and prospective cohort stud- and accounts for much of the age-related increase in In addition to the well-accepted and important relationship of dietary sodium with BP, excessive consump- tion of sodium is independently associated with an increased risk of stroke,S5.2.2-17,S5.2.2-18 and other adverse Certain groups with various demographic, physiological, and genetic characteristics tend to be particularly sensitive to the effects of dietary sodium on BP.S5.2.2-21 S5.2.2-23 Salt sensitivity is a quantitative trait in which an increase in sodium load disproportionately increases BP.S5.2.2-21,S5.2.2-24 Salt sensitivity is especially common in blacks, older adults, and those with a higher level of BP or comorbidities such as CKD, DM, or the metabolic syndrome.S5.2.2-25 In aggregate, these groups constitute more than half of all US adults.S5.2.2-26 Salt sensitivity may be a marker for increased CVD and all-cause mortality risk independently of BP,S5.2.2-27,S5.2.2-28 and the trait has been demonstrated to be reproducible.S5.2.2-29 Current tech- niques for recognition of salt sensitivity are impractical in rou- tine clinical practice, so salt sensitivity is best considered as a group characteristic. Potassium intake is inversely related to BP in migrant,S5.2.3-30 cross- and prospective cohortS5.2.3-33 studies. It is also inversely related to stroke.S5.2.3-34 S5.2.3-36 A higher level of potassium seems to blunt the effect of sodium on BP,S5.2.3-37 with a lower sodium potassium ratio being associated with a lower level of BP than that noted for corresponding levels of sodium or potassium on their Likewise, epidemiological studies suggest that a lower sodium potassium ratio may result in a reduced risk of CVD as compared with the pattern for corresponding levels of either cation on its own.S5.2.3-39 5.2.4. Physical Fitness Epidemiological studies have demonstrated an inverse relation- ship between physical activity and physical fitness and level of BP and hypertension.S5.2.4-40 Even modest levels of physical activity have been associated with a decrease in the risk of inci- In several observational studies, the relationship between physical activity and BP has been most apparent in white men.S5.2.4-40 With the advent of electronic activity trackers and ABPM, it has become increasingly feasi- ble to conduct studies that relate physical activity and BP.S5.2.4-42 Physical fitness, measured objectively by graded exercise testing, attenuates the rise of BP with age and prevents the development of hypertension. In the CARDIA (Coronary Artery Risk Development in Young Adults) study,S5.2.4-43 phys- ical fitness measured at 18 to 30 years of age in the upper 2 deciles of an otherwise healthy population was associated with one third the risk of developing hypertension 15 years later, and one half the risk after adjustment for body mass index, as compared with the lowest quintile. Change in fitness assessed 7 years later further modified risk.S5.2.4-43 In a cohort of men 20 to 90 years of age who were followed longitudi- nally for 3 to 28 years, higher physical fitness decreased the rate of rise in SBP over time and delayed the time to onset of The presence of a direct relationship between alcohol consumption and BP was first reported in 1915S5.2.5-45 and has been repeatedly identified in contemporary cross-sec- tional and prospective cohort studies.S5.2.5-46 Estimates of the contribution of alcohol consumption to population incidence and prevalence of hypertension vary according to level of intake. In the United States, it seems likely that alcohol may account for close to 10% of the population burden of hyper- tension (higher in men than in women). In contrast to its detrimental effect on BP, alcohol intake is associated with Figure 3. Screening for secondary hypertension. Colors correspond to Class of Recommendation in Table 1. TOD indicates target organ damage (eg, cerebrovascular disease, hypertensive retinopathy, left ventricular hypertrophy, left ventricular dysfunction, heart failure, coronary artery disease, chronic kidney disease, albuminuria, peripheral artery disease). Table 13. Causes of Secondary Hypertension With Clinical Indications and Diagnostic Screening Tests Prevalence Clinical Indications Physical Examination Screening Tests Additional/Confirmatory Tests Common causes Renal parenchymal 1% 2% Urinary tract infections; obstruction, hematuria; urinary frequency and nocturia; analgesic abuse; family history of polycystic kidney disease; elevated serum creatinine; abnormal urinalysis Abdominal mass (polycystic kidney disease); skin pallor Renal ultrasound Tests to evaluate cause of renal disease Renovascular Resistant hypertension; hypertension of abrupt onset or worsening or increasingly difficult to control; flash pulmonary edema (atherosclerotic); early-onset hypertension, especially in women (fibromuscular hyperplasia) Abdominal systolic- diastolic bruit; bruits over other arteries (carotid atherosclerotic or fibromuscular dysplasia), femoral Renal Duplex Doppler ultrasound; MRA; abdominal CT Bilateral selective renal intra-arterial angiography Primary 8% 20% Resistant hypertension; hypertension with hypokalemia (spontaneous or diuretic induced); hypertension and muscle cramps or weakness; hypertension and incidentally discovered adrenal mass; hypertension and obstructive sleep apnea; hypertension and family history of early-onset hypertension or stroke Arrhythmias (with hypokalemia); especially atrial fibrillation Plasma aldosterone/ renin ratio under standardized conditions (correction of hypokalemia and withdrawal of aldosterone antagonists for 4 6 wk) Oral sodium loading test (with 24-h urine aldosterone) or IV saline infusion test with plasma aldosterone at 4 h of infusion Adrenal CT scan, adrenal vein sampling. Obstructive sleep 25% 50% Resistant hypertension; snoring; fitful sleep; breathing pauses during sleep; daytime sleepiness Obesity, Mallampati class III IV; loss of normal nocturnal BP fall Berlin Epworth Sleepiness overnight oximetry Polysomnography Drug or alcohol 2% 4% Sodium-containing antacids; caffeine; nicotine (smoking); alcohol; NSAIDs; oral contraceptives; cyclosporine or tacrolimus; sympathomimetics (decongestants, anorectics); cocaine, amphetamines and other illicit drugs; neuropsychiatric agents; erythropoiesis-stimulating agents; clonidine withdrawal; herbal agents (Ma Huang, ephedra) Fine tremor, tachycardia, sweating (cocaine, ephedrine, MAO inhibitors); acute abdominal pain (cocaine) Urinary drug screen (illicit drugs) Response to withdrawal of suspected agent Uncommon causes Pheochromocytoma/para 0.1% 0.6% Resistant hypertension; paroxysmal hypertension or crisis superimposed on sustained hypertension; spells, BP lability, headache, sweating, palpitations, pallor; positive family history of pheochromocytoma/ paraganglioma; adrenal incidentaloma Skin stigmata of neurofibromatosis (caf -au-lait spots; neurofibromas); Orthostatic hypotension fractionated metanephrines or plasma metanephrines under standard conditions (supine position with indwelling IV cannula) CT or MRI scan of abdomen/pelvis Cushing s <0.1% Rapid weight gain, especially with central distribution; proximal muscle weakness; depression; hyperglycemia Central obesity, moon face, dorsal and supraclavicular fat pads, wide (1-cm) violaceous striae, hirsutism dexamethasone suppression test 24-h urinary free cortisol excretion (preferably multiple); midnight salivary cortisol (Continued) Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e31 a higher level of high-density lipoprotein cholesterol and, within modest ranges of intake, a lower level of CHD than that associated with abstinence.S5.2.3-35 5.3. Childhood Risk Factors and BP Tracking BP distribution in the general population increases with age. Multiple longitudinal studies have investigated the relation- ship of childhood BP to adult BP. A meta-analysis of 50 such studies showed correlation coefficients of about 0.38 for SBP and 0.28 for DBP, with BPs in the upper range of the pedi- atric distribution (particularly BPs obtained in adolescence) predicting hypertension in adulthood.S5.3-1 Several factors, including genetic factors and development of obesity, increase the likelihood that a high childhood BP will lead to future Premature birth is associated with a 4 mm Hg higher SBP and a 3 mm Hg higher DBP in adulthood, Uncommon causes (Continued) <1% Dry skin; cold intolerance; constipation; hoarseness; weight gain Delayed ankle reflex; periorbital puffiness; coarse skin; cold skin; slow movement; goiter Thyroid-stimulating hormone; free thyroxine None <1% Warm, moist skin; heat intolerance; nervousness; tremulousness; insomnia; weight loss; diarrhea; proximal muscle weakness Lid lag; fine tremor of the outstretched hands; warm, moist skin Thyroid-stimulating hormone; free thyroxine Radioactive iodine uptake and scan Aortic coarctation (undiagnosed or 0.1% Young patient with hypertension (<30 y of age) BP higher in upper extremities than in lower extremities; absent femoral pulses; continuous murmur over patient s back, chest, or abdominal bruit; left thoracotomy scar (postoperative) Echocardiogram Thoracic and abdominal CT angiogram or MRA Primary hyperpara- Rare Hypercalcemia Usually none Serum calcium Serum parathyroid hormone Congenital adrenal Rare Hypertension and hypokalemia; incomplete masculinization in males and primary amenorrhea in females (17-alpha-hydroxylase Signs of virilization or incomplete masculinization Hypertension and hypokalemia with low or normal aldosterone and renin deoxycorticosterone (DOC), alpha-OH; decreased androgens and estrogen; elevated deoxycorticosterone and corticosterone Mineralocorticoid excess syndromes other than primary Rare Early-onset hypertension; resistant hypertension; hypokalemia or hyperkalemia Arrhythmias (with hypokalemia) Low aldosterone and renin Urinary cortisol metabolites; genetic testing Rare Acral features, enlarging shoe, glove, or hat size; headache, visual disturbances; diabetes mellitus Acral features; large hands and feet; frontal bossing Serum growth hormone 1 ng/mL during oral glucose load Elevated age- and level; MRI scan of the pituitary *Depending on the clinical situation (hypertension alone, 5%; hypertension starting dialysis, 22%; hypertension and peripheral vascular disease, 28%; hypertension in the elderly with congestive heart failure, 34%). 8% in general population with hypertension; up to 20% in patients with resistant hypertension. Although obstructive sleep apnea is listed as a cause of secondary hypertension, RCTs on the effects of continuous positive airway pressure on lowering BP in patients with hypertension have produced mixed results (see Section 5.4.4 for details). For a list of frequently used drugs causing hypertension and accompanying evidence, see Table 14. BP indicates blood pressure; CT, computed tomography; DOC, 11-deoxycorticosterone; IGF-1, insulin-like growth factor-1; IV, intravenous; MAO, monamine oxidase; MRI, magnetic resonance imaging; MRA, magnetic resonance arteriography; NSAIDs, nonsteroidal anti-inflammatory drugs; OH, hydroxylase; and RCT, randomized clinical trial. Table 13. Continued Prevalence Clinical Indications Physical Examination Screening Tests Additional/Confirmatory Tests with somewhat larger effects in women than in men.S5.3-3 Low birth weight from other causes also contributes to higher BP in later life.S5.3-4 5.4. Secondary Forms of Hypertension Recommendations for Secondary Forms of Hypertension COR LOE Recommendations I C-EO 1. Screening for specific form(s) of secondary hypertension is recommended when the clinical indications and physical examination findings listed in Table 13 are present or in adults with resistant hypertension. IIb C-EO 2. If an adult with sustained hypertension screens positive for a form of secondary hypertension, referral to a physician with expertise in that form of hypertension may be reasonable for diagnostic confirmation and treatment. Synopsis A specific, remediable cause of hypertension can be identified in approximately 10% of adult patients with hypertension.S5.4-1 If a cause can be correctly diagnosed and treated, patients with secondary hypertension can achieve a cure or experience a marked improvement in BP control, with reduction in CVD risk. All new patients with hypertension should be screened with a history, physical examination, and laboratory inves- tigations, as recommended in Section 7, before initiation of treatment. Secondary hypertension can underlie severe elevation of BP, pharmacologically resistant hypertension, sud- den onset of hypertension, increased BP in patients with hypertension previously controlled on drug therapy, onset of diastolic hypertension in older adults, and target organ damage disproportionate to the duration or severity of the hypertension. Although secondary hypertension should be suspected in younger patients (<30 years of age) with elevated BP, it is not uncommon for primary hypertension to manifest at a younger age, especially in blacks,S5.4-2 and some forms of secondary hypertension, such as renovas- cular disease, are more common at older age. Many of the causes of secondary hypertension are strongly associated with clinical findings or groups of findings that suggest a specific disorder. Figure 3 is an algorithm on screening for secondary hypertension. Table 13 is a detailed list of clinical indica- tions and diagnostic screening tests for secondary hyperten- sion, and Table 14 is a list of drugs that can induce secondary hypertension. Recommendation-Specific Supportive Text 1. The causes of secondary hypertension and recommend- ed screening tests are provided in Table 13, and drugs that can induce secondary hypertension are provided in Table 14. 2. Diagnosis of many of these disorders requires a complex set of measurements, specialized technical expertise, and/ or experience in data interpretation. Similarly, specific treatment often requires a level of technical training and experience. 5.4.1. Drugs and Other Substances With Potential to Impair BP Control Numerous substances, including prescription medications, over-the-counter medications, herbals, and food substances, may affect BP (Table 14).S5.4.1-1 S5.4.1-6 Changes in BP that occur because of drugs and other agents have been associ- ated with the development of hypertension, worsening con- trol in a patient who already has hypertension, or attenuation of the BP-lowering effects of antihypertensive therapy. A change in BP may also result from drug drug or drug food In the clinical assessment of hyper- tension, a careful history should be taken with regard to sub- stances that may impair BP control, with close attention paid to not only prescription medications, but also over-the-counter substances, illicit drugs, and herbal products. When feasible, drugs associated with increased BP should be reduced or dis- continued, and alternative agents should be used. 5.4.2. Primary Aldosteronism Recommendations for Primary Aldosteronism COR LOE Recommendations I C-EO 1. In adults with hypertension, screening for primary aldosteronism is recommended in the presence of any of the following concurrent conditions: resistant hypertension, hypokalemia (spontaneous or substantial, if diuretic induced), incidentally discovered adrenal mass, family history of early-onset hypertension, or stroke at a young age (<40 years). I C-LD 2. Use of the plasma aldosterone: renin activity ratio is recommended when adults are screened for primary aldosteronism.S5.4.2-1 I C-EO 3. In adults with hypertension and a positive screening test for primary aldosteronism, referral to a hypertension specialist or endocrinologist is recommended for further evaluation and treatment. Synopsis Primary aldosteronism is defined as a group of disorders in which aldosterone production is inappropriately high for sodium status, is relatively autonomous of the major regula- tors of secretion (angiotensin II and potassium), and cannot be suppressed with sodium loading.S5.4.2-2,S5.4.2-3 The increased production of aldosterone induces hypertension; cardiovascu- lar and kidney damage; sodium retention; suppressed plasma renin activity; and increased potassium excretion, which, if prolonged and severe, may cause hypokalemia. However, hypokalemia is absent in the majority of cases and has a low negative predictive value for the diagnosis of primary In about 50% of the patients, primary aldosteronism is due to increased unilateral aldosterone pro- duction (usually aldosterone-producing adenoma or, rarely, unilateral adrenal hyperplasia); in the remaining 50%, pri- mary aldosteronism is due to bilateral adrenal hyperplasia Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e33 Recommendation-Specific Supportive Text 1. Primary aldosteronism is one of the most frequent dis- orders (occurring in 5% to 10% of patients with hyper- tension and 20% of patients with resistant hyperten- sion) that causes secondary hypertension.S5.4.2-5,S5.4.2-6 The toxic tissue effects of aldosterone induce greater target organ damage in primary aldosteronism than in primary hypertension. Patients with primary aldo- steronism have a 3.7-fold increase in HF, a 4.2-fold increase in stroke, a 6.5-fold increase in MI, a 12.1- fold increase in atrial fibrillation (AF), increased left ventricular hypertrophy (LVH) and diastolic dysfunc- tion, increased stiffness of large arteries, widespread tissue fibrosis, increased remodeling of resistance vessels, and increased kidney damage as compared with patients with primary hypertension matched for Because the deleterious effects of aldosterone overproduction are often reversible with unilateral laparoscopic adrenalectomy or treatment with mineralocorticoid receptor antagonists (ie, spi- ronolactone or eplerenone), screening of patients with hypertension at increased risk of primary aldosteron- ism is beneficial.S5.4.2-2,S5.4.2-3 These include hypertensive patients with adrenal incidentaloma, an incidentally discovered adrenal lesion on a computed tomography or magnetic resonance imaging (MRI) scan performed for other purposes. Patients with hypertension and a history of early onset hypertension and/or cerebro- vascular accident at a young age may have primary aldosteronism due to glucocorticoid-remediable al- dosteronism (familial hyperaldosteronism type-1) and therefore warrant screening.S5.4.2-2,S5.4.2-3 2. The aldosterone:renin activity ratio is currently the most accurate and reliable means of screening for primary Table 14. Frequently Used Medications and Other Substances That May Cause Elevated BP* Agent Possible Management Strategy Alcohol Limit alcohol to 1 drink daily for women and 2 drinks for menS5.4.1-7 Amphetamines (eg, amphetamine, methylphenidate dexmethylphenidate, dextroamphetamine) Discontinue or decrease doseS5.4.1-8 Consider behavioral therapies for ADHDS5.4.1-9 Antidepressants (eg, MAOIs, SNRIs, TCAs) Consider alternative agents (eg, SSRIs) depending on indication Avoid tyramine-containing foods with MAOIs Atypical antipsychotics (eg, clozapine, olanzapine) Discontinue or limit use when possible Consider behavior therapy where appropriate Recommend lifestyle modification (see Section 6.2) Consider alternative agents associated with lower risk of weight gain, diabetes mellitus, and dyslipidemia (eg, aripiprazole, ziprasidone)S5.4.1-10,S5.4.1-11 Caffeine Generally limit caffeine intake to <300 mg/d Avoid use in patients with uncontrolled hypertension Coffee use in patients with hypertension is associated with acute increases in BP; long-term use is not associated with increased BP or CVDS5.4.1-12 Decongestants (eg, phenylephrine, pseudoephedrine) Use for shortest duration possible, and avoid in severe or uncontrolled hypertension Consider alternative therapies (eg, nasal saline, intranasal corticosteroids, antihistamines) as appropriate Herbal supplements (eg, Ma Huang [ephedra], St. John s wort [with MAO inhibitors, yohimbine]) Avoid use Immunosuppressants (eg, cyclosporine) Consider converting to tacrolimus, which may be associated with fewer effects on BPS5.4.1-13 S5.4.1-15 Oral contraceptives Use low-dose (eg, 20 30 mcg ethinyl estradiol) agentsS5.4.1-16 or a progestin-only form of contraception, or consider alternative forms of birth control where appropriate (eg, barrier, abstinence, IUD) Avoid use in women with uncontrolled hypertensionS5.4.1-16 NSAIDs Avoid systemic NSAIDs when possible Consider alternative analgesics (eg, acetaminophen, tramadol, topical NSAIDs), depending on indication and risk Recreational drugs (eg, bath salts [MDPV], cocaine, methamphetamine, etc.) Discontinue or avoid use Systemic corticosteroids (eg, dexamethasone, fludrocortisone, methylprednisolone, prednisone, prednisolone) Avoid or limit use when possible Consider alternative modes of administration (eg, inhaled, topical) when feasible Angiogenesis inhibitor (eg, bevacizumab) and tyrosine kinase inhibitors (eg, sunitinib, sorafenib) Initiate or intensify antihypertensive therapy *List is not all inclusive. ADHD indicates attention-deficit/hyperactivity disorder; BP, blood pressure; CVD, cardiovascular disease; IUD, intra-uterine device; MAOI, monoamine-oxidase inhibitors; MDPV, methylenedioxypyrovalerone; NSAIDs, nonsteroidal anti-inflammatory drugs; SNRI, serotonin norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; and TCA, tricyclic antidepressant. The most commonly used cutoff value is 30 when plasma aldosterone concentration is re- ported in nanograms per deciliter (ng/dL) and plasma re- nin activity in nanograms per milliliter per hour (ng/mL/ Because the aldosterone:renin activity ratio can be influenced by the presence of very low renin levels, the plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive.S5.4.2-3 Patients should have unrestricted salt intake, serum potassium in the normal range, and mineralocorticoid receptor antago- nists (eg, spironolactone or eplerenone) withdrawn for at least 4 weeks before testing.S5.4.2-2,S5.4.2-3 3. The diagnosis of primary aldosteronism generally re- quires a confirmatory test (intravenous saline suppression test or oral salt-loading test).S5.4.2-2,S5.4.2-3 If the diagnosis of primary aldosteronism is confirmed (and the patient agrees that surgery would be desirable), the patient is re- ferred for an adrenal venous sampling procedure to de- termine whether the increased aldosterone production is unilateral or bilateral in origin. If unilateral aldosterone production is documented on adrenal venous sampling, the patient is referred for unilateral laparoscopic adrenal- ectomy, which improves BP in virtually 100% of patients and results in a complete cure of hypertension in about If the patient has bilaterally increased aldosterone secretion on adrenal venous sampling or has a unilateral source of excess aldosterone production but cannot undergo surgery, the patient is treated with spi- ronolactone or eplerenone as agent of choice.S5.4.2-2,S5.4.2-3 Both adrenalectomy and medical ktherapy are effective in lowering BP and reversing LVH. Treating primary al- dosteronism, either by mineralocorticoid receptor antag- onists or unilateral adrenalectomy (if indicated), resolves hypokalemia, lowers BP, reduces the number of antihy- pertensive medications required, and improves param- eters of impaired cardiac and kidney function.S5.4.2-9,S5.4.2-10 5.4.3. Renal Artery Stenosis Recommendations for Renal Artery Stenosis References that support recommendations are summarized in Online Data Supplements 7 and 24. COR LOE Recommendations I A 1. Medical therapy is recommended for adults with atherosclerotic renal artery IIb C-EO 2. In adults with renal artery stenosis for whom medical management has failed (refractory hypertension, worsening renal function, and/or intractable HF) and those with nonatherosclerotic disease, including fibromuscular dysplasia, it may be reasonable to refer the patient for consideration of revascularization (percutaneous renal artery angioplasty and/ or stent placement). Synopsis Renal artery stenosis refers to a narrowing of the renal artery that can result in a restriction of blood flow. Atherosclerotic disease (90%) is by far the most common cause of renal artery stenosis, whereas nonatherosclerotic disease (of which fibro- muscular dysplasia is the most common) is much less prevalent and tends to occur in younger, healthier patients.S5.4.3-3 Renal artery stenosis is a common form of secondary hypertension. Relieving ischemia and the ensuing postischemic release of renin by surgical renal artery reconstruction is an invasive strat- egy with a postoperative mortality as high as 13%.S5.4.3-4 With the advent of endovascular procedures to restore blood flow, several trials were designed to test the efficacy of these pro- cedures against medical therapy, but they suggested no benefit over medical therapy alone.S5.4.3-1,S5.4.3-2 Recommendation-Specific Supportive Text 1. Atherosclerotic disease in the renal arteries represents systemic disease and higher risk of both renal failure and cardiovascular morbidity and mortality. No RCT to date has demonstrated a clinical advantage of renal artery revascularization (with either angioplasty or stenting) over medical therapy.S5.4.3-2 On the basis of the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) trial, the recommended medical approach en- compasses optimal management of hypertension with an antihypertensive regimen that includes a renin-angio- tensin system (RAS) blocker, in addition to low-density lipoprotein cholesterol reduction with a high-intensity statin, smoking cessation, hemoglobin A1c reduction in patients with DM, and antiplatelet therapy.S5.4.3-1 2. Revascularization may be considered for those who do not respond to medical therapy and for those who have nonatherosclerotic disease (eg, Takayasu arteritis in Asian populations, fibromuscular dysplasia in other populations). Fibromuscular dysplasia occurs over the lifespan of women (mean: 53 years of age) with almost equal frequency in the renal and carotid circulations.S5.4.3-3 Percutaneous transluminal angioplasty alone (without stenting) can improve BP control and even normalize BP, especially in patients with recent onset of hypertension or 5.4.4. Obstructive Sleep Apnea Recommendation for Obstructive Sleep Apnea References that support the recommendation are summarized in Online Data Supplement 8. COR LOE Recommendation IIb B-R 1. In adults with hypertension and obstructive sleep apnea, the effectiveness of continuous positive airway pressure (CPAP) to reduce BP is not well established.S5.4.4-1 S5.4.4-5 Synopsis Obstructive sleep apnea is a common chronic condition char- acterized by recurrent collapse of upper airways during sleep, inducing intermittent episodes of apnea/hypopnea, hypox- emia, and sleep disruption.S5.4.4-6 Obstructive sleep apnea is a risk factor for several CVDs, including hypertension, coro- nary and cerebrovascular diseases, HF, and AF.S5.4.4-6 S5.4.4-9 Observational studies have shown that the presence of obstruc- tive sleep apnea is associated with increased risk of inci- Obstructive sleep apnea is Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e35 highly prevalent in adults with resistant hypertension and it has been hypothesized that treat- ment with CPAP may have more pronounced effects on BP reduction in resistant hypertension.S5.4.4-6 Recommendation-Specific Supportive Text 1. CPAP is an efficacious treatment for improving obstruc- tive sleep apnea. However, studies of the effects of CPAP on BP have demonstrated only small effects on BP (eg, 2 to 3 mm Hg reductions), with results dependent on patient compliance with CPAP use, severity of obstruc- tive sleep apnea, and presence of daytime sleepiness in Although many RCTs have been reported that address the effects of CPAP on BP in obstructive sleep apnea, most of the patients studied did not have documented hypertension, and the studies were too small and the follow-up period too short to allow for adequate evaluation. In addition, a well-designed RCT demonstrated that CPAP plus usual care, compared with usual care alone, did not prevent cardiovascular events in patients with moderate severe obstructive sleep apnea and established CVD.S5.4.4-14 6. Nonpharmacological Interventions Correcting the dietary aberrations, physical inactivity, and excessive consumption of alcohol that cause high BP is a fundamentally important approach to prevention and man- agement of high BP, either on their own or in combination with pharmacological therapy. Prevention of hypertension and treatment of established hypertension are complemen- tary approaches to reducing CVD risk in the population, but prevention of hypertension provides the optimal means of reducing risk and avoiding the harmful consequences of Nonpharmacological therapy alone is especially useful for prevention of hypertension, including in adults with elevated BP, and for management of high BP in adults with milder forms of hypertension.S6-4,S6-5 Nonpharmacological interventions can be accomplished by means of behavioral strategies aimed at lifestyle change, prescription of dietary supplements, or implementation of kitchen-based interventions that directly modify elements of the diet. At a societal level, policy changes can enhance the availability of healthy foods and facilitate physical activ- ity. The goal can be to modestly reduce BP in the general population or to undertake more intensive targeted lowering of BP in adults with hypertension or at high risk of devel- The intent of the general population approach is to achieve a small downward shift in the general population distribution of BP, which would be expected to result in substantial health benefits.S6.1-2 The targeted approach focuses on BP reduction in adults at greatest risk of develop- ing BP-related CVD, including individuals with hypertension, as well as those at increased risk of developing hypertension, especially blacks and adults who are overweight, consume excessive amounts of dietary sodium, have a high intake of alcohol, or are physically inactive. The targeted approach tends to be intensive, with a more ambitious goal for BP reduction. Both approaches are complementary and mutually reinforcing, and modeling studies suggest they are likely to provide similar public health benefit.S6.1-3,S6.1-4 However, as the precision of risk prediction tools increases, targeted pre- vention strategies that focus on high-risk individuals seem to become more efficient than population-based strategies.S6.1-5 6.2. Nonpharmacological Interventions Recommendations for Nonpharmacological Interventions References that support recommendations are summarized in Online Data Supplements 9-21. COR LOE Recommendations I A 1. Weight loss is recommended to reduce BP in adults with elevated BP or hypertension who are overweight or obese.S6.2-1 S6.2-4 I A 2. A heart-healthy diet, such as the DASH (Dietary Approaches to Stop Hypertension) diet, that facilitates achieving a desirable weight is recommended for adults with elevated BP or I A 3. Sodium reduction is recommended for adults with elevated BP or I A 4. Potassium supplementation, preferably in dietary modification, is recommended for adults with elevated BP or hypertension, unless contraindicated by the presence of CKD or use of drugs that reduce potassium I A 5. Increased physical activity with a structured exercise program is recommended for adults with elevated BP I A 6. Adult men and women with elevated BP or hypertension who currently consume alcohol should be advised to drink no more than 2 and 1 standard drinks* per day, *In the United States, 1 standard drink contains roughly 14 g of pure alcohol, which is typically found in 12 oz of regular beer (usually about 5% alcohol), 5 oz of wine (usually about 12% alcohol), and 1.5 oz of distilled spirits Synopsis Nonpharmacological interventions are effective in low- ering BP, with the most important interventions being the DASH (Dietary Approaches to Stop increased physical and a reduction in alcohol Various other nonpharmacological interventions have been reported to lower BP, but the extent and/or quality of the supporting clinical trial experience is less persuasive. Such interventions include consumption of increased intake of protein,S6.2-35 S6.2-37 or fish oil;S6.2-41 supplementa- tion with calciumS6.2-42,S6.2-43 and use of dietary patterns other than the DASH diet, including low-carbohydrate, vegetarian, and Mediterranean diets.S6.2-46 S6.2-49 Stress reduction is intuitively attractive but insufficiently as are several other interventions, including con- sumption of garlic,S6.2-52 or Behavioral therapies, including guided breathing, yoga, transcendental meditation, and biofeedback, lack strong evidence for their long-term BP-lowering effect.S6.2-51,S6.2-57 S6.2-61 The best proven nonpharmacological measures to prevent and treat hypertension are summarized in Table 15.S6.2-62 The nonpharmacological interventions presented in Table 15 may be sufficient to prevent hypertension and meet goal BP in managing patients with stage 1 hypertension, and they are an integral part of the management of persons with stage 2 hypertension. To a lesser extent, the Mediterranean (which incorporates the basics of healthy eat- ing but emphasizes consumption of legumes and monoun- saturated fat, avoidance of red meats, and moderate intake of wine) has been effective in reducing BP, as well as improving lipid profile. Recommendation-Specific Supportive Text 1. Weight loss is a core recommendation and should be achieved through a combination of reduced calorie intake and increased physical activity.S6.2-1 The BP-lowering effect of weight loss in patients with elevated BP is con- sistent with the corresponding effect in patients with established hypertension, with an apparent dose re- sponse relationship of about 1 mm Hg per kilogram of weight loss. Achievement and maintenance of weight loss through behavior change are challengingS6.2-64 S6.2-66 but feasible over prolonged periods of follow-up.S6.2-64 For those who do not meet their weight loss goals with nonpharmacological interventions, pharmacotherapy or minimally invasive and bariatric surgical procedures can Surgical procedures tend to be more effective but are usually reserved for those with more severe and intractable obesity because of the fre- quency of complications.S6.2-69 2. The DASH eating plan is the diet best demonstrated to be effective for lowering BP. Because the DASH diet is high in fruits, vegetables, and low-fat dairy products, it pro- vides a means to enhance intake of potassium, calcium, magnesium, and fiber. In hypertensive and nonhyperten- sive adults, the DASH diet has produced overall reduc- tions in SBP of approximately 11 mm Hg and 3 mm Hg, and the diet was especially effective When combined with weight lossS6.2-6 or a reduction in sodium intake,S6.2-5,S6.2-30 the effect size was substantially increased. Most of the clinical trial Table 15. Best Proven Nonpharmacological Interventions for Prevention and Treatment of Hypertension* Nonpharmacological Intervention Dose Approximate Impact on SBP Hypertension Normotension Reference Weight loss Weight/body fat Best goal is ideal body weight, but aim for at least a 1-kg reduction in body weight for most adults who are overweight. Expect about 1 mm Hg for every 1-kg reduction in body weight. Healthy diet DASH dietary pattern Consume a diet rich in fruits, vegetables, whole grains, and low-fat dairy products, with reduced content of saturated and total fat. Reduced intake of dietary sodium Dietary sodium Optimal goal is <1500 mg/d, but aim for at least a 1000-mg/d reduction in most adults. Enhanced intake of dietary potassium Dietary potassium Aim for 3500 5000 mg/d, preferably by consumption of a diet rich in potassium. Physical activity Aerobic 90 150 min/wk 65% 75% heart rate reserve Dynamic resistance 90 150 min/wk Isometric resistance 4 2 min (hand grip), 1 min rest between exercises, 30% 40% maximum voluntary contraction, 3 sessions/wk Moderation in alcohol intake Alcohol consumption In individuals who drink alcohol, reduce alcohol to: Men: 2 drinks daily Women: 1 drink daily Resources: Your Guide to Lowering Your Blood Pressure With DASH How Do I Make the DASH? Available at: https://www.nhlbi.nih.gov/health/resources/heart/ hbp-dash-how-to. Accessed September 15, 2017.S6.2-72 Top 10 Dash Diet Tips. Available at: http://dashdiet.org/dash_diet_tips.asp. Accessed September 15, 2017.S6.2-73 *Type, dose, and expected impact on BP in adults with a normal BP and with hypertension. In the United States, one standard drink contains roughly 14 g of pure alcohol, which is typically found in 12 oz of regular beer (usually about 5% alcohol), 5 oz of wine (usually about 12% alcohol), and 1.5 oz of distilled spirits (usually about 40% alcohol).S6.2-29 DASH indicates Dietary Approaches to Stop Hypertension; and SBP, systolic blood pressure. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e37 experience comes from short-term feeding studies,S6.2-7 but lifestyle change with the DASH diet has been suc- cessful in at least 2 trials that used a behavioral inter- vention over a 4-monthS6.2-30 period of follow-up. Websites and books provide advice on imple- mentation of the DASH diet.S6.2-13,S6.2-71 S6.2-74 Counseling by a knowledgeable nutritionist can be helpful. Several other diets, including diets that are low in calories from vegetarian and a Mediterranean dietary pattern,S6.2-49,S6.2-63 have been shown to lower BP. 3. Sodium reduction interventions prevent hypertension and lower BP in adults with hypertension, especially in those with higher levels of BP, blacks, older persons, and others who are particularly susceptible to the effects of sodium on BP.S6.2-8 S6.2-11 Sodium reduction interventions may prevent CVD.S6.2-76,S6.2-77 Lifestyle change (behavior- al) interventions usually reduce sodium intake by about 25% (approximately 1000 mg per day) and result in an average of about a 2 mm Hg to 3 mm Hg reduction in SBP in nonhypertensive individuals, though the reduc- tion can be more than double this in more susceptible individuals, those with hypertension, and those con- currently on the DASH dietS6.2-5 or receiving a weight Sodium reduction in adults with hypertension who are already being treated with BP- lowering medications further reduces SBP by about 3 mm Hg and can facilitate discontinuation of medica- tion, although this requires maintenance of the lifestyle change and warrants careful monitoring.S6.2-12 When combined with weight loss, the reduction in BP is al- most doubled. A reduction in sodium intake may also lower SBP significantly in individuals with resistant hypertension who are taking multiple antihypertensive (see Section 11.1). Reduced dietary sodium has been reported to augment the BP-lowering effects of RAS blocker therapy.S6.2-79 Maintenance of the lifestyle changes necessary to reduce sodium in- take is challenging,S6.2-2 S6.2-4,S6.2-12 but even a small decrement in sodium consumption is likely to be es- pecially in those whose BP is salt sensitive.S6.2-82 In the United States, most dietary sodium comes from addi- tions during food processing or during commercial food preparation at sit-down and fast-food restaurants.S6.2-83,S6.2-84 Person-specific and policy approaches can be used to reduce dietary sodium intake.S6.2-85,S6.2-86 Individuals can take action to reduce their dietary intake of sodium by choice of fresh foods, use of food labels to choose foods that are lower in sodium content, choice of foods with a no added sodium label, judicious use of condiments and sodium-infused foods, use of spices and low-sodium flavorings, careful ordering when eating out, control of food portion size, and avoiding or minimizing use of salt at the table. Dietary counseling by a nutrition- ist with expertise in behavior modification can be help- ful. A reduction in the amount of sodium added during food processing, as well as fast food and restaurant food preparation, has the potential to substantially reduce so- dium intake without the need for a conscious change in 4. Dietary potassium is inversely related to BP and hy- pertension in migrant studies,S6.2-88 cross-sectional and prospective cohort studies.S6.2-92 Likewise, dietary potassiumS6.2-93 S6.2-96 and a high in- take of fruits and vegetables are associated with a lower incidence of stroke.S6.2-97 Potassium interventions have been effective in lowering BP,S6.2-13,S6.2-14,S6.2-16,S6.2-81 especially in adult patients consuming an excess of and in blacks.S6.2-13 The typical BP-lowering effect of a 60-mmol (1380-mg) adminis- tration of potassium chloride has been about 2 mm Hg and 4 to 5 mm Hg in adults with normotension and hypertension, respectively, although the response is up to twice as much in persons consuming a high-sodium diet. A reduction in the sodium/potassium index may be more important than the corresponding changes in either electrolyte alone.S6.2-99 Some but not all studies suggest that the intervention effect may be restricted to adult patients with a low (1500-mg to 2000-mg) daily intake of potassium.S6.2-92,S6.2-100 Most of the intervention experience comes from trials of relatively short duration but the BP-lowering effect of potassium in adult patients consuming a high- sodium diet has been reproduced after an interval of 4.4 In most trials, potassium supplementation was achieved by administration of potassium chloride pills, but the BP response pattern was similar when di- etary modification was used.S6.2-13 Because potassium- rich diets tend to be heart healthy, they are preferred over use of pills for potassium supplementation. The 2015 Dietary Guidelines for AmericansS6.2-101 encourage a diet rich in potassium and identify the adequate intake level for adult patients as 4700 mg/day.S6.2-102 The World Health Organization recommends a potassium intake of at least 90 mmol (3510 mg) per day from food for adult Good sources of dietary potassium include fruits and vegetables, as well as low-fat dairy products, selected fish and meats, nuts, and soy products. Four to five servings of fruits and vegetables will usually provide 1500 to >3000 mg of potassium. This can be achieved by a diet, such as the DASH diet, that is high in potassium 5. A BP-lowering effect of increased physical activity has been repeatedly demonstrated in clinical trials, espe- cially during dynamic aerobic exercise,S6.2-18,S6.2-20,S6.2-22 but also during dynamic resistance trainingS6.2-18,S6.2-21 and static isometric exercise.S6.2-18,S6.2-19,S6.2-31 The average reductions in SBP with aerobic exercise are approxi- mately 2 to 4 mm Hg and 5 to 8 mm Hg in adult patients with normotension and hypertension, respectively.S6.2-18 Most trials have been of relatively short duration, but increased physical activity has been an intrinsic compo- nent of longer-term weight reduction interventions used to reduce BP and prevent hypertension.S6.2-3,S6.2-4,S6.2-12 BP-lowering effects have been reported with lower- and higher-intensity exercise and with continuous and in- terval exercise training.S6.2-18,S6.2-103 Meta-analyses sug- gest isometric exercise results in substantial lowering of 6. In observational studies, there is a strong, predictable di- rect relationship between alcohol consumption and BP, especially above an intake of 3 standard drinks per day (approximately 36 ounces of regular beer, 15 ounces of wine, or 4.5 ounces of distilled spirits).S6.2-29,S6.2-104,S6.2-105 Meta-analyses of RCTs that have studied the effect of reduced alcohol consumption on BP in adults have iden- tified a significant reduction in SBP and DBP.S6.2-23,S6.2-24 The benefit has seemed to be consistent across trials, but confined to those consuming 3 drinks/day, as well as dose dependent, with those consuming 6 drinks/day at baseline who reduce their alcohol intake by about 50%, experiencing an average reduction in SBP/DBP of ap- Only limited in- formation is available on the effect of alcohol reduction on BP in blacks.S6.2-23,S6.2-106 In contrast to its effect on BP, alcohol seems to have a beneficial effect on several bio- markers for CVD risk, including high-density lipoprotein Observational studies have shown a relatively consistent finding of an inverse relationship between alcohol intake and CHD,S6.2-109,S6.2-110 within a moderate range (approximately 12 14 and 9 standard drinks/week for men and women, respectively). On bal- ance, it seems reasonable for those who are consuming moderate quantities of alcohol ( 2 drinks/day) to con- tinue their moderate consumption of alcohol. 7. Patient Evaluation The patient evaluation is designed to identify target organ damage and possible secondary causes of hypertension and to assist in planning an effective treatment regimen. Historical features are relevant to the evaluation of the patient (Table 16). The pattern of BP measurements and changes over time may differentiate primary from secondary causes of hypertension. A rise in BP associated with weight gain, lifestyle factors (such as a job change requiring travel and meals away from home), reduced frequency or intensity of physical activity, or advancing age in a patient with a strong family history of hypertension would suggest the diagnosis of primary hyper- tension. An evaluation of the patient s dietary habits, physi- cal activity, alcohol consumption, and tobacco use should be performed, with recommendation of the nonpharmacological interventions detailed in Section 6.2 where appropriate. The history should also include inquiry into possible occurrence of symptoms to indicate a secondary cause (Tables 13 and 16). The patient's treatment goals and risk tolerance should also be elicited. This is especially true for older persons, for whom an assessment of multiple chronic conditions, frailty, and prognosis should be performed, including consideration of the time required to see benefit from intervention, which may not be realized for some individuals. The physical examination should include accurate measure- ment of BP (Table 8). Automated oscillometric devices provide an opportunity to obtain repeated measurements without a pro- vider present, thereby minimizing the potential for a white coat effect. Change in BP from seated to standing position should be measured to detect orthostatic hypotension (a decline >20 mm Hg in SBP or >10 mm Hg in DBP after 1 minute is abnor- mal). For adults 30 years of age with elevated brachial BP, a thigh BP measurement is indicated; if the thigh measurement is lower than arm pressures, a diagnosis of coarctation of the aorta should be considered. The physical examination should include assessment of hypertension-related target organ dam- age. 