1. What is the epidemiology of hypertension?

Hypertension remains a common disease among Americans. Data from the National Health and Nutrition Examination Survey reveal that 29% of Americans are hypertensive; this prevalence rate has remained stable for the past 15 years. African Americans bear the highest burden, as over 41% are hypertensive. Other racial groups (i.e. Whites, Asians, and Hispanics) demonstrate hypertension prevalence of 25% to 28%. During this time period, blood pressure (BP) control has improved, largely through the increased use of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), and thiazide-type diuretics in single-pill or multiple-pill combinations. In 2001 to 2002, only 45% of treated hypertensive patients achieved control, defined as BPs <140/90 mm Hg (or <130/80 mm Hg for diabetic patients or chronic kidney disease [CKD] patients [patients with estimated glomerular filtration rates (GFR) <60 mL/min per 1.73 m ² or urinary albumin concentrations >200 mg/g creatinine]). By 2009 to 2010, 60% of treated hypertensive patients had achieved control. However, BP control remains difficult for African Americans, Hispanics, patients with diabetes, and CKD patients. Compared to Caucasians, African Americans and Hispanics are 1.4- and 1.3-fold less likely to achieve control. Again, the greater use of thiazide-type diuretics improves BP control for African Americans. Nearly 70% of treated hypertensive patients without significant comorbidities achieved control by 2009 to 2010, though only approximately 45% of patients with either diabetes mellitus or CKD achieved control.

Obesity complicates hypertension treatment. A cross-sectional study of German hypertensive patients showed that obese patients (i.e., patients with body mass indices ≥30 kg/m ² ) are 1.4- to 2-fold less likely to achieve BP control, compared to normal weight hypertensive patients. While

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  12% of Americans are currently diabetic

  
  
  
  
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    by 2050, diabetic prevalence may increase to more than 25%

  
  
  
  
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  36.5% of Americans are currently obese

  
  
  
  
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    by 2030, 41% may be obese, and 11% may be severely obese

  
  
  
  
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  15% of Americans suffer from CKD

  
  
  
  
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    by 2030, the prevalence of CKD in adults over the age of 30 may be close to 50%

  
  

Recent epidemiologic studies confirm the association of albuminuria and poor BP control in patients with CKD. In a study of 232 US veterans with CKD, proteinuria, not estimated GFR, was found to be an independent predictor of systolic BP. Among the independent predictors of hypertension (age, race, and number of antihypertensive medications), proteinuria most strongly correlated with hypertension. Compared to estimated GFR, albuminuria (or proteinuria) is a stronger determinant of hypertension; albuminuria is also a stronger determinant of poor BP control.

2. What is the cardiovascular disease risk?

The World Health Organization estimates that hypertension is directly responsible for 13% of all deaths worldwide, and its effect is largely independent of a country’s underlying wealth. The Center for Disease Control and Prevention determined that hypertension-related deaths for Americans 45 years of age and older (i.e., hypertension was listed as a cause of death on death certificates) increased 62% between 2000 and 2013, though, as a primary cause of death, hypertension remained stable during this time period (17.5% of all deaths). The Prospective Studies Collaboration, a meta-analysis of 1 million patients, showed that cardiovascular mortality risk began with BPs as low as 115/75 mm Hg, and, for patients 40 to 69 years old, each 20/10 mm Hg increase in BP increased cardiovascular mortality 2-fold.

Whether a J-curve—the point at which low BPs treated within the physiologic range increase cardiovascular risk—exists, is controversial. This is of interest, as the coronary arteries receive significant perfusion during diastole; low diastolic BPs may predispose patients to adverse outcomes. The Prospective Studies Collaboration did not note a J-curve, though older studies have, especially in hypertensive patients with underlying cardiovascular disease who achieve diastolic BPs <85 to 90 mmHg.

CKD imparts increased cardiovascular risk as well. A large meta-analysis of nearly 267,000 patients with diabetes mellitus, hypertension, or cardiovascular disease showed that both low estimated GFRs and albuminuria independently increased all-cause and cardiovascular mortality. Compared to patients with an estimated GFR of 95, cardiovascular mortality risk increased 73% in patients with an estimated GFR of 45, and increased 208% in patients with an estimated GFR of 15. Patients with albumin-to-creatinine ratios of 10, 30, and 300 mg/g experienced a 13%, 55%, and 159% increase in cardiovascular mortality risk, compared to patients with an albumin-to-creatinine ratio of 5 mg/g.

3. Should diastolic, systolic, or pulse pressure be used as a treatment target?

Studies for more than 25 years old have consistently shown that systolic BPs correlate more closely to cardiovascular outcomes and mortality than diastolic BPs, at least for older patients. However, diastolic BPs do provide important prognostic information for younger patients (i.e., those younger than 50 years). As patients age, arterial stiffening occurs, which impairs the buffering of the systolic impulse and causes an increase in the reflected wave. With increased arterial stiffening, systolic pressure rises and diastolic pressure falls.

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  For patients <50 years of age, every 10 mm Hg increase in diastolic BP increases relative cardiovascular risk by 34%.

  
  
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  Patients ≥ 60 years of age, every 10 mm Hg increase in pulse pressure increases cardiovascular risk 24%.

  
  
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  Diastolic and systolic BPs provide equal cardiovascular risk information for patients 50 to 59 years of age.

Patients with CKD, despite being younger, often have increased arterial stiffness and systolic hypertension. Arterial stiffness worsens with higher stages of kidney disease. Therefore among patients with CKD, systolic hypertension should be the major target for treatment.

4. What BP measurement technique should be used?

Hypertension trials use standardized clinic blood measurements to assess the efficacy of treatment regimens and BP targets. Data from these trials have been used to set BP treatment guidelines. Unfortunately, in the day-to-day world of clinical practice, standardized clinic BPs are rarely obtained, as they are technically demanding and time consuming. Improper techniques of measuring BPs correlates poorly with ambulatory BPs, which is currently considered the gold standard for BP measurement. A patient undergoing ambulatory BP monitoring wears a BP cuff for 24 hours. The BP data provided by 24-hour monitoring correlate more closely than clinic BPs, both routine and standardized, to target organ damage and cardiovascular outcomes. Both the United States and the United Kingdom advocate for the use of ambulatory BP monitoring when diagnosing patients with hypertension. Unfortunately, ambulatory BP monitoring, while considered cost effective in hypertension management, still remains largely relegated to clinical trials. An acceptable surrogate for ambulatory BP monitoring is home BP monitoring. Patients performing home BP monitoring obtain BPs in their usual settings. These data provide more information about kidney and cardiovascular risk than clinic BPs. Patients should be advised to use validated monitors. Clinicians may find a list of validated monitors at the Dabl Educational website ( http://www.dableducational.org/index.html ). A minimum of 12 BP recordings, obtained over 1 week, should be used for clinical decision making.

A recent development in BP measurement technique is automated office BP monitoring. Automated office BP measurements are obtained using either a BPTru or an Omron HEM-907. BPTru does not require a period of seated rest whereas the Omron device can be programmed to measure BP only after 5 minutes of seated rest is completed. With both devices, however, medical personnel are not in the room during the measurement. Both are validated machines that are capable of measuring clinic BP while a patient is sitting quietly alone in an examination room. Because medical personnel are absent, the white coat effect (i.e., the artificially elevated BP caused by a patient’s alerting reaction in the clinical setting) is avoided.

Automated office BPs are lower than routine and standardized clinic BPs, though each measurement technique correlates poorly to ambulatory BP measurements. However, as a predictor of target organ damage, automated office BP measurements are superior, as recently demonstrated in a trial of 275 veterans with CKD. Routine clinic BPs were measured after study participants had undergone echocardiography, and automated office BPs were measured using the Omron HEM-907 after participants had rested quietly alone for 5 minutes. Three measurements, 30 seconds apart, were obtained and averaged. Both routine clinic and automated office BP measurements did not predict daytime ambulatory BPs particularly well. Routine clinic systolic BPs were, on average, 4.8 mm Hg higher than daytime ambulatory systolic BPs, though they could underestimate daytime ambulatory systolic BPs by nearly 27 mm Hg or overestimate by 36.5 mm Hg. The automated office systolic BP data were not much better. They were, on average, 7.9 mm Hg lower than daytime ambulatory systolic BPs; they could underestimate daytime ambulatory systolic BPs by 33.2 mm Hg or overestimate 17.4 mm Hg. However, as a predictor of left ventricular hypertrophy, automated office systolic BPs performed significantly better than routine clinic systolic BPs, and they were almost superior to the predictive ability of daytime ambulatory systolic BPs.

5. What are the blood pressure treatment goals?

The optimal blood pressure level for a patient is controversial. The panel that convened for the Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) published recommendations in early 2014. The members limited themselves to review only randomized, controlled trials. JNC 8 published a number of controversial recommendations:

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  Patients with diabetes and chronic kidney disease, the goal clinic blood pressure changed from <130/80 mm Hg to <140/90 mm Hg, as results from trials such as the ACCORD, REIN-2, AASK, and MDRD did not reveal that lower clinic blood pressures improved outcomes in these groups.

  
  
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  Based upon trials such as the HYVET, Syst-Eur, and SHEP, patients ≥60 years without diabetes mellitus or chronic kidney disease achieve a goal clinic blood pressure <150/90 mm Hg, while those <60 years achieve a blood pressure <140/90 mm Hg.

Many experts found this last recommendation troubling, as they felt it predisposed high-risk patients (e.g., older African Americans with hypertension) to lax blood pressure control and increased cardiovascular risk over time. Most international guidelines recommend changing the 60-year-old cut-off to 80 years of age or older.

In November of 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) published joint guidelines for the diagnosis and management of hypertension. The following terms were defined based on clinic blood pressures obtained in a standardized manner:

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  Normal blood pressure: systolic pressure <120 mm Hg, diastolic pressure is <80 mm Hg

  
  
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  Elevated blood pressure: systolic pressure 120 to 129 mm Hg, and diastolic pressure is <80 mm Hg

  
  
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  Stage 1 hypertension: systolic blood pressure of 130 to 139 mm Hg, or a diastolic blood pressure of 80 to 89 mm Hg

  
  
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  Stage 2 hypertension: systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure of ≥90 mm Hg

All patients should receive nonpharmacological therapy if they have elevated clinic blood pressures, stage 1 hypertension, or stage 2 hypertension. Those patients with ≥10 % risk of developing atherosclerotic cardiovascular disease over 10 years ( http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/ ) or with known cardiovascular disease should be treated pharmacologically if they have stage 1 hypertension. All patients, regardless of cardiovascular disease status, should receive pharmacological therapy if they have stage 2 hypertension.

The SPRINT trial called attention to the way blood pressure is measured. Automated office blood pressure monitoring was employed in the SPRINT trial by using the Omron HEM-907 device. The study protocol mandated that patients sit quietly for five minutes prior to the machine taking three measurements at one-minute intervals. The blood pressure measurements were then averaged. The trial randomized three groups of hypertensive patients ≥50 years at high risk for cardiovascular events:

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  Chronic kidney disease patients

  
  
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  Patients with known cardiovascular disease with an estimated 10-year Framingham risk score >15%

  
  
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  Patients with ≥75 years

The two blood pressure targets were either a systolic blood pressure <120 mm Hg or <140 mm Hg. The intensively treated group achieved a systolic blood pressure of 121.5 mm Hg, whereas the control group achieved a systolic blood pressure of 134.6 mm Hg. After a little more than three years of follow-up, the trial was stopped prematurely because of a 25% relative risk reduction among the intensive group in the primary endpoint. The primary endpoint was a combination of cardiovascular outcomes including cardiovascular mortality. Furthermore, a 27% relative risk reduction in all-cause mortality was seen. When interpreting the SPRINT results, one must be cautious not to directly compare these data to other hypertension trials that obtained clinic blood pressures using either oscillometric or mercury cuffs operated by medical personnel without the mandated period of five minutes of seated rest. Thus applying either the JNC 8 or the ACC/AHA recommendations in a post-SPRINT world becomes problematic. Automated office blood pressures generally run 5 to 10 mm Hg lower than traditionally obtained clinic blood pressures. The Canadian Hypertension Education Program now recommends that the cutoff for diagnosing hypertension by automated office blood pressure monitoring be <135/85 mm Hg, instead of <140/90 mm Hg. However, it is unlikely that an algebraic manipulation alone will be useful for individual level decision-making.

Out-of-office blood pressures are also generally lower than traditional clinic blood pressures. Recent ambulatory blood pressure thresholds have been published:

For awake ambulatory blood pressures:

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  For men without high-risk disease, the goal blood pressure is <135/85 mm Hg

  
  
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  For women without high-risk disease, the goal blood pressure is <125/80 mm Hg

  
  
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  For hypertensive patients with diabetes or chronic kidney disease, the goal blood pressure is <120/75 mm Hg

For home blood pressures the American Heart Association recommends

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  Hypertensive patients without high-risk disease a blood pressure goal of <135/85 mm Hg

  
  
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  Diabetic and chronic kidney disease patients with hypertension a blood pressure goal of <130/80 mm Hg