A new study by investigators at Brigham and Women’s Hospital puts the results of a landmark trial about blood pressure control into terms that may be easier to interpret and communicate to patients.
When data from The Systolic Blood Pressure Intervention Trial (SPRINT) were published in 2015, the medical community responded enthusiastically to the news that reducing blood pressure lower than the normal targets could reduce overall death rates by 27 percent for adults at high cardiovascular risk.
While these study results are being integrated into clinical practice, explaining what they mean and why they are important to patients can be challenging.
Investigators from the Brigham describe how aggressively lowering blood pressure levels can extend a person’s life expectancy.
They report that having a blood pressure target of less than 120 mm Hg — rather than the standard 140 mm Hg — can add six months to three years to a person’s lifetime, depending upon how old they are when they begin intensive blood pressure control. Results are published in JAMA Cardiology.
“When physicians discuss optimizing blood pressure, patients often wonder what benefits they may anticipate with intensive blood pressure control,” said lead author Muthiah Vaduganathan, MD, MPH, a cardiologist at the Brigham.
“That was the inspiration for our work: We’ve taken the data and reframed it to contextualize the results in a way that’s most meaningful to patients.”
Vaduganathan and colleagues used age-based methods to conduct their analysis.
These methods are frequently used in other fields — for instance, when projecting the long-term survival benefits of a new cancer drug — but have not been commonly applied in studying cardiovascular disease.
By applying age-based methods to the data from SPRINT, the team could estimate the long-term benefits of intensive blood pressure control.
The SPRINT study enrolled more than 9,000 adults who were 50 years or older, were at high cardiovascular risk but did not have diabetes, and had a systolic blood pressure between 130- and 180-mm Hg (130 mm Hg or higher is considered high blood pressure).
Participants were randomized to intensive (at least 120 mm Hg) or standard (at least 140 mm Hg) systolic blood pressure targets.
Participants were given antihypertensive therapies, free of cost, to achieve their blood pressure targets and were followed for an average of a little over three years.
The authors note that the analysis did not account for potential risks, including kidney injury and low blood pressure, that are associated with intensive blood pressure control.
Vaduganathan and colleagues estimated that if people had continued taking their antihypertensive therapies for the remainder of their lives, those with the intensive blood pressure target could add six months to three years to their life expectancy, compared to those with the standard blood pressure target.
This span depended upon the person’s age — for someone who began antihypertensive medications at 50 years old, they predicted a difference of 2.9 years; for someone 65 years old, a difference of 1.1 years; and for someone 80 years old, a difference of nine months.
The authors note that the analysis did not account for potential risks, including kidney injury and low blood pressure, that are associated with intensive blood pressure control.
Estimates of survival benefits must be carefully weighed against these potential risks in the selection of blood pressure targets for individual patients.
“Our hope is that these findings offer a more easily communicated message when discussing the potential benefits and risks of sustained blood pressure control over time,” said Vaduganathan.
“These statistics about life expectancy may be more tangible and personalized for patients and more relatable when making these decisions.”
The current definition of hypertension (HTN) is systolic blood pressure (SBP) values of 130mmHg or more and/or diastolic blood pressure (DBP) more than 80 mmHg. Hypertension ranks among the most common chronic medical condition characterized by a persistent elevation in the arterial pressure.
Hypertension has been among the most studied topics of the previous century and has been one of the most significant comorbidities contributing to the development of stroke, myocardial infarction, heart failure, and renal failure.
The definition and categories of hypertension have been evolving over years, but there is a consensus that persistent BP readings of 140/90mmHg or more should undergo treatment with the usual therapeutic target of 130/80mmHg or less.
This article will attempt to review the available knowledge derived from RCTs and the recent updates and guidelines on hypertension put forward by major societies including those from the 8th report of Joint National Committee (JNC-8), American College of Cardiology (ACC), American Society of Hypertension (ASH), European Society of Cardiology (ESC) and European Society of Hypertension (ESH).
Most cases of hypertension are idiopathic which is also known as essential hypertension. It has long been suggested that an increase in salt intake increases the risk of developing hypertension. One of the described factors for the development of essential hypertension is the patient genetic ability to salt response. About 50 to 60% of the patients are salt sensitive and therefore tend to develop hypertension.
More than one billion adults worldwide have hypertension with up to 45% of the adult populace being affected with the disease. The high prevalence of hypertension is consistent across all socio-economic and income strata, and the prevalence rises with age accounting for up to 60% of the population above 60 years of age.
In the year 2010, the global health survey report was published in Lancet, which comprised of patient data from 67 countries, reported Hypertension as the leading cause of death and disability-adjusted life years worldwide since the year 1990.
In the United States, HTN alone accounts for more cardiovascular disease-related deaths than any other modifiable risk factor and is second only to cigarette smoking as a preventable cause of death for any reason.
Recent estimates have suggested the number of patients with hypertension could increase as much as by 15 to 20%, which could reach close to 1.5 billion by 2025.
There are various mechanisms described for the development of hypertension which includes increased salt absorption resulting in volume expansion, an impaired response of the renin-angiotensin-aldosterone system (RAAS), increased activation of the sympathetic nervous system. These changes lead to the development of increased total peripheral resistance and increased afterload which in turn leads to the development of hypertension.
History and Physical
Most cases of hypertension are asymptomatic and are diagnosed incidentally on blood pressures recording or measurement.
Some cases present directly with symptoms of end-organ damage as stroke-like symptoms or hypertensive encephalopathy, chest pain, shortness of breath and acute pulmonary edema.
Physical examination may be unyielding other than occasional pedal edema or raised blood pressure, but one needs to look for signs of:
- Coarctation of the aorta (radio-radial delay, radio-femoral delay, differences in left and right arm BP or upper and lower limb BP more than 20mmHg)
- Aortic valve disease (systolic ejection murmur, 4th heart sound)
- Renovascular disease or fibromuscular dysplasia (FMD) – (renal bruit, carotid bruit)
- Polycystic kidneys (enlarged kidneys bilaterally)
- Endocrine disorders [hypercortisolism(thin skin, easy bruising, hyperglycemia)
- Thyroid disorders(palpable/ painful or enlarged thyroid] which make up the common treatable causes for secondary hypertension
The presence of a 4th heart sound, which represents a stiff and non-compliant left ventricle, hints towards left ventricular hypertrophy and diastolic dysfunction.
Presence of lung rales and/or peripheral edema suggests cardiac dysfunction and gives a clue to the chronicity of hypertension.
The ACC recommends at least two office measurement on at least two separate occasions to diagnose hypertension.
The ESC/ESH recommends three office BP measurements at least 1 to 2 minutes apart, and additional measurements only if the initial two readings differ by greater than or equal to 10mmHg. BP is then recorded as the average of the last two readings.
Both societies endorse the use of higher BP readings and putting patients into higher stage/grade for adequate medical therapy.
The patient should remain seated quietly for at least 5 minutes before taking the blood pressure, and proper technique is necessary. The blood pressure cuff should cover 80% of the arm circumference because larger or smaller pressure cuffs can falsely under-estimate or over-estimate blood pressure readings.
Ambulatory blood pressure measurement is the most accurate method to diagnose hypertension and also aids in identifying individuals with masked hypertension as well as white coat effect.
The evaluation consists of looking for signs of end-organ damage and consists of the following,
- 12 lead ECG (to document left ventricular hypertrophy, cardiac rate, and rhythm)
- Fundoscopy to look for retinopathy/ maculopathy
- Blood workup including complete blood count, ESR, creatinine, eGFR, electrolytes, HbA1c, thyroid profile, blood cholesterol levels, and serum uric acid
- Urine albumin to creatinine ratio
- Ankle-brachial pressure index – ABI (if symptoms suggestive of peripheral arterial disease)
- Imaging including carotid doppler ultrasound, echocardiography and brain imaging (where clinically deemed feasible)
Treatment / Management
The management of hypertension subdivides into pharmacological and nonpharmacological management.
Non-pharmacological and lifestyle management are recommended for all individuals with raised BPs regardless of age, gender, comorbidities or cardiovascular risk status.
Patient education is paramount to effective management and should always include detailed instructions regarding weight management, salt restriction, smoking management, adequate management of obstructive sleep apnea and exercise. Patients need to be informed and revised at every encounter that these changes are to be continued lifelong for effective disease treatment.
Weight reduction is advisable if obesity is present although optimum BMI and optimal weight range is still unknown. Weight reduction alone can result in decreases of up to 5 to 20mmHg in systolic blood pressure.
Smoking may not have a direct effect on blood pressure but will help in reducing long term sequelae if the patient quits smoking.
Lifestyle changes alone can account for up to 15% reduction in all cardiovascular-related events.
Pharmacological therapy consists of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), diuretics (usually thiazides), calcium channel blockers (CCBs) and beta-blockers (BBs), which are instituted taking into account age, race and comorbidities such as presence of renal dysfunction, LV dysfunction, heart failure and cerebrovascular disease. JNC-8, ACC, and ESC/ ESH have their separate recommendations for pharmacological management.
JNC-8 recommends the following:
- Starting pharmacological therapy for individuals with DM and CKD with BP greater than or equal to 140/90mmHg to therapeutic target BP less than 140/90mmHg
- Starting pharmacological therapy for individuals 60 years of age and over with BP greater than or equal to 150/90mmHg to therapeutic target BP less than 150/90mmHg
- Starting pharmacological therapy for individuals 18 to 59years of age with SBP greater than or equal to 140mmHg to therapeutic target SBP less than 140mmHg
- individuals with DM and non-black population, treatment should include a thiazide diuretic, CCB, and an ACEi/ARB
- individuals in the black population, including those with DM, treatment should include a thiazide diuretic and CCB
- individuals with CKD, treatment should be started with or include ACEi/ARB, and this applies to all CKD patients irrespective of race or DM status
- Ten-year atherosclerotic cardiovascular disease (ASCVD) risk should be estimated
- Anti-hypertensive medications are usually initiated when BP readings are persistently greater than or equal to 140/90mmHg
- High-risk population (diabetics, CKD, individuals with ASCVD) or in those individuals with 10-year ASCVD risk greater than or equal to 10%, therapy can be initiated at lower BP cutoffs
- The goal of treatment is to keep blood pressures in as close to normal range as possible, i.e., BP less than or equal to 130/80mmHg
ESC/ ESH recommends the following:
- Starting pharmacological therapy for grade 2 or 3 hypertension regardless of the level of risk
- Starting pharmacological therapy for grade 1 hypertension when there is hypertension mediated end-organ damage (HMOD)
- Grade 1 hypertension in the absence of HMOD requires either high risk for CVD or failure of lifestyle interventions, for initiating pharmacological therapy
- Starting pharmacological therapy for individuals greater than or equal to 80 years of age with BP greater than or equal to 160/90mmHg to therapeutic target less than 160/90mmHg regardless of DM, CKD, CAD or TIA/ CVA
- Starting pharmacological therapy for individuals 18 to 79 years of age with BP greater than or equal to 140/90mmHg to therapeutic target less than 140/90mmHg regardless of DM, CKD, CAD or TIA/ CVA
Researchers have also studied renal denervation is a form of interventional treatment where renal sympathetic supply is ablated, via specialized catheter equipment, as a potential treatment for resistant hypertension (where adequate blood pressure control is not achieved despite adequate compliance to two or three anti-hypertensive drugs and lifestyle measures).
Multiple randomized trials including SPYRAL, RADIANCE, and SIMPLICITY-HTN trials have shown equivocal results, so this remains an investigational therapy.
Secondary hypertension should always be sought for as the differential especially if the patient is at extremes of age (young or elderly).
Hyperaldosteronism, coarctation of the aorta, renal artery stenosis, chronic kidney disease, and aortic valve disease should always be kept in the differential.
Pertinent Studies and Ongoing Trials
The SYST-EUR trial, HYVET and SHEP studies were amongst the large RCTs that formed the basis for recommendations from the 8th report of JNC.
The SPRINT trial, HOPE-3 trial, Gubbio population study, Framingham heart study along with other RCTs, formed the basis for recommendations from ACC and ESC/ESH guidelines.
Polytherapy has become the mainstay of treatment and is endorsed and recommended by ACC as well as ESC/ ESH.
There have been two main approaches:
- Either instituting two or more drugs (usually an ACEi or an ARB along with thiazide diuretic and calcium channel blocker) simultaneously, or
- Stepwise titration approach with single therapy being up-titrated to maximum dosage before instituting a second drug.
Both have been successful in improving patient outcomes provided there is adequate compliance and treatment adherence.
All the societies recommend at least an 8 to 12-week duration of anti-hypertensive medication before assessing BP control and reviewing patient for complications.
There is a consensus that home BP measurements or ABPM should be checked at or before initiation of therapy and then three months after starting therapy for monitoring and documentation of adequate BP control.
Toxicity and Side Effect Management
Side effects are generally mild and resolve promptly upon decreasing the dosage or discontinuing the drug for short intervals.
Patients should be frequently monitored for side effects, more so in the early initiation phase of therapy when they are much frequent. Side effects are usually self-limited and include hypotension (more common with calcium channel blockers (CCBs) and ACEi/ ARBs), electrolyte imbalances, pedal edema (more common with CCBs) and renal dysfunction. Renal dysfunction and electrolyte imbalance especially hyponatremia and hyperkalemia are frequent with ACEi and ARBs and need to be monitored periodically until the achievement of static levels of Cr, K, and Na.
For patients with severe side effects like symptomatic hyperkalemia or hyponatremia, syncope and acute kidney injury (AKI), treatment needs to be discontinued, and in-patient management is advised. Nephrologist and cardiologist opinions also need to be sought in such cases. Once the issues settle, treatment needs to be re-instituted gradually and cautiously with careful monitoring and frequent follow-ups.
Angioedema has been a potentially life-threatening side effect of ACEi and ARBs in susceptible individuals and warrants prompt discontinuation and is also a lifelong contra-indication for ACEi/ ARB usage.
Classification and stages of hypertension as defined in recent American College of Cardiology (ACC) guidelines are as under
- Normal: SBP less than 120 and DBP less than 80mmHg;
- Elevated: SBP 120 to 129 and DBP less than 80mmHg;
- Stage 1 hypertension: SBP 130 to 139 or DBP 80 to 89mmHg;
- Stage 2 hypertension: SBP greater than or equal to 140 mmHg or greater than or equal to 90 mmHg.
White coat hypertension is an office BP 130/80 mmHg or more but less than 160/100mmHg which comes down to 130/80mmHg or less after at least 3 months of anti-hypertensive therapy. Ambulatory or home blood pressure measurement is usually necessary for this diagnosis.
Masked hypertension is an elevated office systolic BP 120 to 129mmHg, and diastolic BP less than 80mmHg but raised BP on ambulatory or home measurements (130/80mmHg or more).
The ACC classification came out in 2017, received an endorsement from the ASH, and recommended for individuals aged 20 years and above.
The recent ESC/ESH guidelines came out in 2018 and defined Hypertension as under
- Optimal: SBP less than 120mmHg and DBP less than 80mmHg
- Normal: SBP 120 to 129mmHg and/or DBP 80 to 84mmHg
- High normal: SBP 130 to 139mmHg and/or DBP 85 to 89mmHg
- Grade 1 hypertension: SBP 140 to 159mmHg and/or DBP 90 to 99mmHg
- Grade 2 hypertension: SBP 160 to 179mmHg and/or DBP 100 to 109mmHg
- Grade 3 hypertension: SBP greater than or equal to 180mmHg and/or DBP greater than or equal to 110mmHg
- Isolated systolic hypertension: SBP greater than or equal to 140mmHg and DBP less than 90mmHg (further classified into Grades as per above ranges of SBP)
ESC/ESH recommendations also shed light on home (HBPM) and ambulatory BP measurements (ABPM) and following cut-offs were given
- Daytime (or awake) mean SBP greater than or equal to 135mmHg and/or DBP greater than or equal to 85mmHg
- Night-time (or asleep) mean SBP greater than or equal to 120mmHg and/or DBP greater than or equal to 70mmHg
- 24 hr mean SBP greater than or equal to 130mmHg and/or DBP greater than or equal to 80mmHg
- Home BP mean SBP greater than or equal to 135mmHg and/or DBP greater than or equal to 85mmHg
The ESC/ESH recommendations applied to individuals aged 16 years and above.
The 8th report of Joint National Committee (JNC) came out in 2014 and received heavy criticism across the globe, did not address the definition of hypertension but put forward its recommendations based on previous definitions put forward by JNC-7. The ESC/ ESH classification came out in 2018 and is to be used in all individuals of ages 16 years and above.
- Normal: SBP less than 120mmHg and DBP less than 80mmHg
- Pre-Hypertension: SBP 120 to 139mmHg and DBP 80 to 89mmHg
- Stage 1 Hypertension: SBP 140 to 159mmHg and DBP 90 to 99mmHg
- Stage 2 Hypertension: SBP greater than or equal to 160mmHg and DBP greater than or equal to 100mmHg
The JNC-8 recommendations were exclusively for individuals aged 18 years and above.
Large scale metanalyses have also shown the rising CVD and vascular disease risk with a rise in systolic and diastolic blood pressures, with almost doubling of risk of death from heart disease and stroke with rising SBP of as much as 20 and DBP of 10mmHg.
The prognosis depends on blood pressure control and is favorable only if the blood pressures attain adequate control; however, complications may develop in some patients as hypertension is a progressive disease.
Adequate control and lifestyle measures only serve to delay the development and progression of sequelae such as chronic kidney disease and renal failure.
- Coronary heart disease (CHD)
- Myocardial infarction (MI)
- Stroke (CVA), either ischemic or intracerebral hemorrhage
- Hypertensive encephalopathy
- Renal failure, acute versus chronic
- Peripheral arterial disease
- Atrial fibrillation
- Aortic aneurysm
- Death (usually due to coronary heart disease, vascular disease, stroke-related)
In the case of resistant hypertension, a multi-disciplinary approach merits consideration.
A cardiologist, nephrologist and hypertension specialist should manage such patients in consort.
Often patients will also require psycho-social counseling and consultation with nutritionists and dieticians.
Brigham and Women’s Hospital