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Hunter Mwansa, MD, St. Vincent Charity Medical Center, Case Western Reserve University, Cleveland, OH
Sula Mazimba, MD, MPH, Division of Cardiovascular Medicine, University of Virginia Health System, Charlottesville
Glen D. Solomon, MD, FACP, Professor and Chair, Department of Internal Medicine, Wright State University, Boonshoft School of Medicine, Dayton, OH
Hypertension is a common and serious condition that contributes to an estimated 40% of deaths from coronary heart disease and stroke, and is the second leading cause of end-stage renal disease.
Because of the importance and frequency of hypertension in primary care practices, we are devoting two issues to the subject. This issue focuses on the definition of blood pressure and current guidelines, risk factors, relationship to cardiovascular disease, blood pressure measurement, patient evaluation, and secondary causes. The next issue will cover treatments (pharmacological and non-pharmacological), initial therapy, relationship to various disease conditions (diabetes, ischemic heart disease, heart failure, chronic kidney disease, cerebrovascular disease, ischemic stroke, stroke prevention, atrial fibrillation, valvular heart disease, aortic regurgitation, sexual dysfunction), resistant hypertension, hypertensive crises and emergencies, preoperative management, and adherence strategies.
— Gregory R. Wise, MD, FACP, Editor
Hypertension (HTN) is a leading cause of death and morbidity worldwide.1,2 The burden and prevalence of the disease is increasing globally. The annual rate of death and disability-adjusted life-years associated with a systolic blood pressure (SBP) ≥ 140 mmHg increased from 97.9 to 106.3 per 100,000 persons and 5.2 million to 7.8 million, respectively, between 1990 and 2015. 2 HTN also is associated with increased cardiovascular disease (CVD) risk as well as being a major cause of death in western countries.3 In the United States, HTN is associated with more CVD deaths than any other modifiable disease condition.4 For example, according to data from an epidemiological study, the National Health and Nutrition Examination Survey (NHANES), involving 23,272 participants, an estimated 50% of deaths from coronary heart disease (CHD) and stroke were attributable to HTN.5 In another epidemiological cohort, the Atherosclerosis Risk in Communities study, HTN contributed to about 25% of CVD events (CHD, coronary revascularization, stroke, or heart failure).6 HTN is also the second leading cause of end-stage renal disease (ESRD) among patients with kidney disease in the United States (34% of incident ESRD).7
Based on the 2017 American College of Cardiology/American Heart Association (ACC/AHA) consensus guidelines, HTN recently was redefined as blood pressure (BP) ≥ 130/80 mmHg (from a previous threshold of 140/80 mmHg).8 However, this new definition has not received universal endorsement. The American Academy of Family Physicians and American College of Physicians have opposed these new guidelines and published their own consensus statements.9 The new systolic BP diagnostic threshold (also a therapeutic target goal) has been the focus of contention. Opponents of the new ACC/AHA guidelines contend that there may be a potential for more harm than benefit, especially among elderly patients with adoption of these strict criteria.9 Also, they further contend that the ACC/AHA guidelines lend more weight to evidence derived from the Systolic Blood Pressure Intervention Trial (SPRINT) and less consideration of the systematic review of other scientific data. From an epidemiological standpoint, the new definition for HTN translates to a net increase in the prevalence of the HTN among U.S. adults. In a recent study, researchers estimated that the overall prevalence of HTN in the United States will increase to 45.4% of the population (105 million adults) from 32.0% (74.1 million) when compared to the 2014 guidelines.10 Overall, the prevalence of HTN is not distributed uniformly across the U.S. population. The prevalence of HTN increases with age, and is higher among blacks than age- and sex-matched Caucasian, Asian, and Hispanic Americans.8 The heterogeneity in the prevalence of HTN could be attributable partly to the national obesity trends as well as the increasing segment of the population that is elderly. For example, the prevalence of obesity among U.S. adults aged ≥ 20 years was 56.0% and 69.0% in the NHANES 1988-1994 and 2011-2014, respectively, and these rates correspond to HTN prevalence rates of 28.8% and 32.0% for the same period using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) BP definitions. The Framingham Heart Study reported a 90% life-time risk of developing HTN for non-hypertensive adults aged 55 or 65 years in both men and women,11,12 while some studies estimate more than a 50% prevalence of HTN in adults aged 60 to 69 years and 75% prevalence for those aged 70 years or older.13 The lifetime risk of developing HTN is higher among African Americans and Hispanics than whites and Asians.12
In the last several decades, substantial progress has been made in the general awareness, treatment, and control of HTN. However, patients with HTN still have an increased risk of adverse CVD events compared to those without HTN.5 For example, in the NHANES 2009-2012 report, prevalence estimates were 80.2% and 85.4% for awareness, 70.9% and 80.6% for treatment, 69.5% and 68.5% for control among those on therapy, and 49.3% and 55.2% for overall control in adult men and women with HTN, respectively.14 These estimates were based on previous HTN guidelines (BP ≥ 140/90 mmHg for diagnosis and BP ≤ 140/90 mmHg for control). The number of adults with uncontrolled HTN has improved over the years, but challenges still persist, especially for those between the ages of 18 and 39 years and those ≥ 75 years of age in whom control rates are still low, 34.4% and 46%, respectively, based on data from the NHANES 2009-2012. There also are persistent and unique challenges of racial and gender disparities in the control of HTN. For example, BP control in blacks and Hispanics is disproportionately lower than in whites. Control rates among black and Hispanic men and women are 31.1% and 23.6%, respectively, and 43.3% and 52.9%, respectively, compared to 41.3% and 57.2% for white men and women, respectively, during the 2009-2012 time frame.15 Achieving greater control of HTN is desirable from a public health standpoint to mitigate the adverse events associated with the disease. In general, about 12.3% of hypertensive U.S. adults have an average SBP ≥ 160 mmHg or average diastolic blood pressure (DBP) ≥ 100 mmHg, highlighting the critical areas for improvement given that uncontrolled HTN leads to increased incidence of preventable ischemic heart disease, kidney disease, stroke, and death.16
HTN commonly occurs in individuals with other CVD risk factors. Table 1 shows modifiable and non-modifiable risk factors for the disease.
Based on data from the NHANES 2009-2012, among U.S. adults with HTN, 63.2% also had hypercholesterolemia, 49.5% were obese, 27.2% had diabetes mellitus, 15.8% had chronic kidney disease (CKD; defined as estimated glomerular filtration rate [eGFR] < 60 mL/min and/or urine albumin to creatinine ratio ≥ 300 mg/g), and 15.5% were also current smokers.17 These data highlight the fact that HTN is coexistent with other CVD risk factors. The clustering of multiple CVD risk factors in patients with HTN translates into increased absolute CHD and stroke risk. A study of U.S. adults with HTN between 2009 and 2012 reported a 10-year risk of CHD > 20%, 10-20%, and < 10% for 41.7%, 40.9%, and 18.4% of all participants, respectively.17 Hypertensive adults with two or more CVD risk factors have a significantly higher risk of CVD death, nonfatal myocardial infarction (MI), and fatal or nonfatal stroke than those with only one risk factor.17,18 Treatment of modifiable risk factors can help prevent and/or control BP with eventual reduction in the global CVD risk burden.
Notwithstanding, some patients with HTN have underlying genetic predisposition.19 Additionally, lifestyle factors, including high sodium intake, obesity, excessive alcohol intake, and certain medications (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs], stimulants, and decongestants) may induce or aggravate HTN and make it difficult to control.20,21,22
Elevations in SBP and/or DBP are associated with increased CVD risk.23,24 CVD risk is increased in a log-linear pattern from SBP < 105 mmHg to > 180 mmHg and from DBP < 75 mmHg to > 105 mmHg, according to a meta-analysis of 61 prospective trials.23 These authors further reported a doubling of risk for death from stroke, heart disease, or other vascular disease with a rise in SBP and DBP by 20 mmHg and 10 mmHg, respectively.
An observational study involving more than 1 million adults ≥ 30 years of age reported an increased incidence in CVD, heart failure (HF), cerebrovascular accidents (CVA), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA) with higher SBP and DBP when the two were evaluated independently.24 These findings are consistent with observations from the Framingham Heart Study demonstrating that individuals with SBP between 130-139 mmHg and DBP between 85-89 mmHg had twice as high relative risk of cardiovascular mortality compared to those with normal BP using the JNC 7 criteria.25 This graded dose-response relationship of BP thresholds and cardiovascular outcomes has served as the impetus for recommending more stringent HTN cutoffs (BP ≥ 130/80 mmHg) by the ACC/AHA. The rationale for this strict BP threshold is to enable identification of “normal BP” by JNC 7 guidelines in patients for whom early lifestyle intervention measures may vitiate the progression of HTN.8,26
Others have raised concern that the label “prehypertension” in the previous iterations of guidelines may have led to “therapeutic inertia” resulting in less care.27 The 2017 ACC/AHA guidelines on HTN also place emphasis on reducing the global CVD risk of a patient. In this vein, the guidelines recommend estimating the 10-year risk of cardiovascular disease to allow for individualized care (http://tools.acc.org/ASCVD-Risk-Estimator/). As previously stated, there has been no universal endorsement of these guidelines. Some sections of the medical community have argued that lowering the BP threshold for diagnosis of HTN may be misinterpreted to be a mandate for unwarranted pharmacologic therapy with potential for harm in patients with minimal CVD risk.27 Another concern is that the 10% 10-year-risk designation advocated in the ACC/AHA guidelines is not strongly supported by evidence from randomized, controlled trials (RCTs). The SPRINT trial that formed the foundation for this recommendation had enrolled patients with more comorbid conditions (15% or higher Framingham risk scores) to identify patients who would benefit from an intensive BP treatment strategy. Thus, critics contend that the sicker SPRINT trial population is not easily generalizable to the general population.27
In a break from the JNC 8 Expert Panel on BP, the ACC/AHA guidelines were lowered across the board even for people aged 65 years or older. A SPRINT subgroup analysis showed benefit from an intense BP control strategy, even in those 75 years of age or older, without significant differences in adverse events reported (including hypotension, syncope, and electrolyte abnormalities) between the two trial arms. There are genuine concerns for potentially serious adverse effects with intense therapy in the debilitated and frail elderly. Theoretically, elderly patients, especially those with poor vascular compliance (pulse pressures > 80-90 mmHg), may experience dizziness and poor mentation with tight BP control. Further, the new BP guidelines failed to address the challenge of diastolic HTN. As opposed to SBP, DBP elevation has not been associated consistently with increased CVD risk.28,29 However, it is important to note that DBP < 60 mmHg in patients with diabetes and those with CAD has been associated with higher risks of progressive kidney disease and ischemic heart disease.30 Given these considerations, a balanced approach anchored firmly on a careful assessment of patient risk and strong clinical judgment is advised in the application of guidelines on HTN. Table 2 compares definitions and classification of HTN between the JNC 7 and the 2017 ACC/AHA guidelines.
Unlike DBP, SBP consistently has been associated with CVD risk in multiple studies.28,29 However, some studies suggest that DBP might be a more potent risk factor for CVD than SBP in those younger than 50 years of age, following which age SBP assumes a greater role in CVD risk.31 The aging process is associated with reduced compliance of the arterial vasculature leading to vascular stiffness.31 For this reason, isolated SBP is common in the elderly population. The age-related increase in central arterial stiffness results in greater peripheral runoff during systole and less blood in the aorta during diastole that culminate in low DBP.32 Therefore, aging is associated with an increase in pulse pressure (PP), the difference between SBP and DBP. Both SBP and PP are major predictors of cardiovascular mortality in people older than 60 years of age.31 Treatment of isolated SBP reduces overall mortality, cardiovascular mortality, and development of HF.33,34
Obtaining accurate and valid BP measurements is essential in categorizing BP level, diagnosis, and appropriate management of HTN. BP measurements are best obtained using a well-functioning and validated BP measuring device. Concerns for mercury spillages with potential toxicity have led to increased adoption of oscillometric devices that rely primarily on sensors to detect oscillations in pulsatile blood volume during cuff inflation and deflation. Aneroid manometers and automated electronic devices now are widely available. However, these BP measuring devices must be validated and calibrated periodically. Table 3 highlights a summary of steps necessary in ensuring accurate BP measurement.8
Out of office BP measurement and self-monitoring of BP allow for regular measurement of BP at home or elsewhere. Interestingly, there is evidence to suggest BP reduction is achieved readily with self-monitoring of BP in hypertensive subjects.35,36,37 These reductions in SBP and DBP may be even more pronounced when self-monitoring is used in conjunction with other interventions. More recently, it has been observed that there are frequent discordances between office and out of office BP measurements, with some advocating for increased use of out-of-office BP measurements to ascertain correct BP measurements.8 The two main methods commonly used for out-of-office BP measurements are home BP measurement (HBPM) and ambulatory BP measurement (ABPM). ABPM allows for BP measurement during routine daily activities and is preferred to HBPM. However, HBPM is more practical and can be reliable if the BP measuring device is validated and properly calibrated and the patient is educated on proper use. Office BP rates generally are higher than both ambulatory and home BP rates, especially in those with higher blood pressures. In general, office BP of 130/80 mmHg corresponds to HBPM BP of 130/80 mmHg and to average ABPM BPs of 130/80 mmHg, 110/65 mmHg, and 125/75 mmHg for daytime, nighttime, and 24 hours, respectively.8 Additionally, office BP of 140/90 mmHg corresponds to HBPM BP of 135/85 mmHg and to average ABPM BPs of 135/85 mmHg, 120/70 mmHg, and 130/80 mmHg for daytime, nighttime, and 24 hours, respectively.38,39 It is important to ensure that patients are well-educated on proper BP measuring techniques. (See Table 3.)
ABPM devices are programmed to obtain readings every 15 to 30 minutes throughout the day and every 15 to 60 minutes during the night. Other than providing reliable measures of BP, ABPM devices also give clinically relevant trends on nocturnal BP dipping through provision of daytime to nighttime BP ratio. The device also might help identify early-morning BP surge, 24-hour BP variability, and symptomatic hypotension. Because of this difference in office, HBPM, and ABPM BP values, different BP thresholds have been advanced to categorize high BP with use of HBPM and ABPM, but general consensus still is lacking. Previously, the JNC 7 suggested diagnosis of HTN in individuals with ambulatory daytime BP ≥ 135/85 mmHg and BP ≥ 120/75 mmHg during sleep.26 This recommendation was driven partly by evidence that individuals with average ambulatory BP readings > 135/85 mmHg have a two-fold increased incidence of cardiovascular events compared to those with BP < 135/85 mmHg.40 ABPM is indicated in individuals with suspected white-coat and masked HTN, resistant HTN, hypotensive symptoms with antihypertensive medication, and episodic HTN.
HBPM and ABPM make further stratification of BP into several clinically useful categories possible. White coat HTN is characterized by elevated office BP, but normal readings on ABPM or HBPM. The “white coat” effect is considered significant when office SBPs/DBPs are > 20/10 mmHg than home or ambulatory SBP/DBPs. It is important to recognize white coat HTN, since it has been implicated in pseudo-resistant HTN, leads to underestimation of office BP control,41 and can be a cause of unnecessary intensification of antihypertensive therapy. The prevalence of white coat HTN is between 13% and 35%.42,43 White coat HTN rarely progresses to sustained HTN in those who are older and obese,44 and has been associated with a slightly increased risk of CVD and all-cause mortality risk.45,46,47 Conversely, masked HTN is characterized by normal office BP but elevated out-of-office (HBPM or ABPM) BP readings. Estimates from population-based surveys suggest a prevalence of 10% to 26% and 14% to 30% for masked HTN in population-based surveys and normotensive office populations, respectively.48,49,50 However, masked HTN is associated with a two-fold increased CVD and all-cause mortality compared to that seen in normotensive individuals.51 Thus, HBPM and ABPM serve to identify patients with white coat and masked HTN.
Masked uncontrolled HTN, an entity analogous to masked HTN, is characterized by office BP readings suggestive of adequate control but HBPM or ABPM readings that are consistently above BP goal.52 Masked uncontrolled HTN seems to have a CVD risk profile similar to that of masked HTN,53 but the therapeutic implications of identifying it remain unclear. It appears reasonable to screen patients with increased CVD risk or target organ damage for masked uncontrolled HTN.
Evaluation of the patient with HTN is focused on achieving the following goals:
1. Identification of potentially reversible individual patient lifestyle risk factors, cardiovascular risk factors, and comorbid diseases;
2. Identification of potential secondary causes of HTN; and
3. Assessment of target organ damage.
The above goals also may prove useful in guiding patient management. Obtaining a detailed history and thorough physical exam might help identify potentially reversible risk factors, secondary causes, comorbid medical conditions, and complications of HTN. History might aid in differentiating between primary (essential) and secondary HTN. Some clues from a patient’s history for essential HTN include a family history of HTN, advancing age, overweight/obesity, physical inactivity, and high sodium intake. Therefore, clinicians must inquire about a patient’s dietary habits, physical activity, tobacco use, and alcohol use. It is also important to look for comorbid medical conditions and associated complications such as diabetes, dyslipidemia, HF, obstructive sleep apnea, CVAs, PAD, and renal disease. Vigilance for secondary causes of HTN is key. (See Table 4.)
Therefore, reviewing medications and determining recreational drug use are crucial to the identification of reversible factors that might need to be addressed to help manage HTN. History can provide clues to the severity of HTN, including the presence of underlying end-organ damage. For example, chest pain and dyspnea in a hypertensive patient may signal cardiac complications including CAD and pulmonary edema. Headaches, visual disturbances, focal weakness, and confusion might occur in individuals with hypertensive retinopathy, CVA, and hypertensive encephalopathy. The presence of target organ damage signals the need for more aggressive BP control. A physical exam must focus on identifying possible causes of HTN (see Table 4) while also evaluating for target organ damage. The correct measurement of BP is crucial. (See Table 3.) Upper extremity (arm) BPs must be compared to mid-thigh BPs in those with suspected coarctation of the aorta. In select patients, orthostatic hypotension must be measured correctly (a decline in SBP > 20 mmHg or DBP > 10 mmHg after one minute on movement from supine to standing position). Patients with pheochromocytoma may be orthostatic. The body mass index (BMI) and waist circumference, especially for patients of South Asian descent, both must be determined. Fundoscopy must be done to assess for retinopathy in those patients presenting with hypertensive emergency. Presence of thyromegaly in the right clinical context may point to pre-existing thyroid disease. Presence of tremors might signal hyperthyroidism. Radial and femoral pulses must be assessed (atrial fibrillation is not uncommon in patients with HTN, and presence of radio-femoral delay may suggest aortic coarctation). A displaced apical impulse and presence of an S4 gallop on cardiac exam may point to long-standing HTN complicated by left ventricular hypertrophy (LVH). Hypertensive patients whose clinical course is complicated by HF may have physical evidence of volume overload, such as jugular venous distension, S3 gallop, pulmonary edema, hepatomegaly, and lower extremity edema. It is important to elicit for carotid and abdominal bruits, as their presence may suggest renovascular HTN. A palpable flank or abdominal mass might be a clue for polycystic kidney disease. A palpable abdominal bruit may suggest AAA. The pulmonary exam might reveal pulmonary edema in patients with a hypertensive emergency. A neurological exam must be conducted, paying close attention to neurological deficits pointing to prior CVAs, ruptured aneurysms, or vascular emergencies depending on the acuity of presentation.
Initial laboratory evaluation in a newly diagnosed hypertensive patient helps establish a baseline electrolyte status prior to medication use, CVD risk status, and ongoing medication monitoring for possible complications arising from therapy (e.g., renal dysfunction). Importantly, initial evaluation may help diagnose secondary causes of HTN.8 (See Table 4.)
The cost implications and lack of established effect on CVD risk reclassification and therapy preclude routine echocardiography in asymptomatic hypertensive patients. However, it must be noted that LVH as measured by electrocardiography, echocardiography, and magnetic resonance imaging is an independent predictor of CVD complications.54 In fact, reduction in LVH may predict a reduction in CVD risk independent of BP reduction.54 Routine testing to evaluate for secondary causes of HTN is not recommended. Evaluation for secondary causes of HTN might be necessary in those with onset of HTN at age < 30 years or > 55 years, increasing or sudden difficulty to control HTN despite prior adequate control, resistant HTN, historical or clinical clues suggestive of secondary HTN, and target organ damage disproportionate to level of BP elevation.8 Table 5 provides a list of important investigations in newly diagnosed hypertensive patients.
Secondary HTN is defined as elevated BP in the setting of identifiable and often correctable underlying disease. The prevalence of secondary HTN previously has been estimated at 5-10%.55
Table 4 provides a comprehensive review of identifiable causes of HTN, including renovascular disease (5-34%), obstructive sleep apnea (25-50%), primary aldosteronism (8-20%), drug- and alcohol-related (2-4%), and renal parenchymal disease (1-2%). Rarely, secondary HTN is attributable to pheochromocytoma (0.1-0.6%), hypothyroidism (< 1%), hyperthyroidism (< 1%), Cushing’s syndrome (< 0.1%), and coarctation of aorta (0.1%). Estimates on renovascular HTN are highly variable and depend on the cohort under consideration. For example, its prevalence is only 5% in those with HTN alone compared to a prevalence of 28% in those with HTN and peripheral vascular disease.56 Furthermore, estimates of prevalence of primary aldosteronism in the general population with HTN are 8% compared to 20% in those with resistant HTN.57
HTN is a major public health problem both in the United States and globally. The attendant high mortality and morbidity associated with HTN warrant concerted efforts aimed at prompt diagnosis along with vigilant screening for comorbid conditions that synergistically raise the risk profile for cardiovascular events. Secondary HTN is not uncommon and should be sought in the right clinical context.
Financial Disclosure: To reveal any potential bias in this publication, and in accordance with Accreditation Council for Continuing Medical Education guidelines, Dr. Wise (editor) reports he is involved with sales for CNS Vital Signs, Clean Sweep, and Admera Health. Dr. Mwansa (author), Dr. Mazimba (author), Dr. Solomon (peer reviewer), Ms. Coplin (executive editor), Ms. Mark (executive editor), and Ms. Hatcher (editorial group manager) report no financial relationships with companies related to the field of study covered by this CME activity.