HYPERTENSION

EPIDEMIOLOGY

Hypertension is counted as the major cause and most important factor in the development of cardiovascular diseases worldwide.⁽¹⁾ At present, it is estimated that about 1 billion people worldwide have hypertension (>140 / 90 mmHg), and this number is expected to increase to 1.56 billion by 2025.⁽²⁾ 

According to Pakistan National Health Survey (1990-94) survey, 17.9% of the population over the age of 15 years and 33% over the age of 45years were labeled as hypertensive (>140 / 90 mmHg). A similar prevalence (15% over the age of 18 years and 36% over the age of 45years) was reported by another survey conducted in the Northern Areas of Pakistan.⁽³⁾

CLASSIFICATION OF HYPERTENSION:

Based on recommendations of the JNC 7, the classification of BP (expressed in mm Hg) for adults aged 18 years or older is as follows:⁽⁴⁾

• Normal: systolic lower than 120 mm Hg, diastolic lower than 80 mm Hg
• Prehypertension: systolic 120-139 mm Hg, diastolic 80-89 mm Hg
• Stage 1: systolic 140-159 mm Hg, diastolic 90-99 mm Hg
• Stage 2: systolic 160 mm Hg or greater, diastolic 100 mm Hg or greater

Prehypertension, a new category designated in the JNC 7 report, emphasizes that patients with prehypertension are at risk for progression to hypertension and that lifestyle modifications are important preventive strategies.

PATHOPHYSIOLOGY:

The pathogenesis of essential hypertension is multifactorial and highly complex.⁽⁵⁾ Multiple factors modulate the blood pressure (BP) for adequate tissue perfusion and include humoral mediators, vascular reactivity, circulating blood volume, vascular caliber, blood viscosity, cardiac output, blood vessel elasticity, and neural stimulation. A possible pathogenesis of essential hypertension has been proposed in which multiple factors, including genetic predisposition, excess dietary salt intake, and adrenergic tone, may interact to produce hypertension. Although genetics appears to contribute to essential hypertension, the exact mechanism has not been established.

Due to investigations into the pathophysiology of hypertension, both in animals and humans, growing evidence suggest that hypertension may have an immunological basis. Studies have revealed that hypertension is associated with renal infiltration of immune cells and that pharmacologic immunosuppression (such as with the drug mycophenolate mofetil) or pathologic immunosuppression (such as occurs with HIV) results in reduced blood pressure in animals and humans. Evidence suggests that T lymphocytes and T-cell derived cytokines (e.g. interleukin 17, tumor necrosis factor alpha) play an important role in hypertension.

One hypothesis is that prehypertension results in oxidation and altered mechanical forces that lead to the formation of neoantigens, which are then presented to T cells, leading to T-cell activation and infiltration of critical organs (e.g. kidney, vasculature). This results in persistent or severe hypertension and end organ damage. Sympathetic nervous system activation and noradrenergic stimuli have also been shown to promote T-lymphocyte activation and infiltration and contribute to the pathophysiology of hypertension.^(6-8)

One mechanism of hypertension has been described as high-output hypertension. High-output hypertension results from decreased peripheral vascular resistance and concomitant cardiac stimulation by adrenergic hyperactivity and altered calcium homeostasis. A second mechanism manifests with normal or reduced cardiac output and elevated systemic vascular resistance due to increased vasoreactivity. Another (and overlapping) mechanism is increased salt and water reabsorption (salt sensitivity) by the kidney, which increases circulating blood volume.

Cortisol reactivity, an index of hypothalamic-pituitary-adrenal function, may be another mechanism by which psychosocial stress is associated with future hypertension.⁽⁸⁾  In a prospective substudy of the Whitehall II cohort, with 3 years follow-up of an occupational cohort in previously healthy patients, investigators reported 15.9% of the patient sample developed hypertension in response to laboratory-induced mental stressors and found an association between cortisol stress reactivity and incident hypertension.⁽⁹⁾

NATURAL HISTORY:

The natural history of essential hypertension evolves from occasional to established hypertension. After a long invariable asymptomatic period, persistent hypertension develops into complicated hypertension, in which end-organ damage to the aorta and small arteries, heart, kidneys, retina, and central nervous system is evident.

The progression of essential hypertension is as follows:

1. Prehypertension in persons aged 10-30 years (by increased cardiac output)
2. Early hypertension in persons aged 20-40 years (in which increased peripheral resistance is prominent)
3. Established hypertension in persons aged 30-50 years
4. Complicated hypertension in persons aged 40-60 years

SIGN AND SYMPTOMS:

High blood pressure usually causes no symptoms and high blood pressure often is labeled "the silent killer." People who have high blood pressure typically don't know it until their blood pressure is measured.

Sometimes people with markedly elevated blood pressure may develop:

• Headache
• Dizziness
• Blurred vision
• Nausea and vomiting
• Chest pain and shortness of breath.

COMPLICATIONS OF HYPERTENSION:

Each of the following complications is closely associated with the presence of hypertension:

• Left ventricular hypertrophy (LVH) is a common and early finding in patients with hypertension.⁽¹⁰⁾ LVH is associated with a higher incidence of subsequent heart failure, myocardial infarction, sudden death, and stroke.⁽¹¹⁾
• The risk of heart failure, both systolic (reduced ejection fraction) and diastolic (preserved ejection fraction), increases with the degree of blood pressure elevation.⁽¹²⁾ The pathogenesis of heart failure in patients with hypertension is both ischemic and non-ischemic.
• Hypertension is the most common and most important risk factor for ischemic stroke, the incidence of which can be markedly reduced by effective antihypertensive therapy.⁽¹³⁾
• Hypertension is the most important risk factor for the development of intracerebral hemorrhage.⁽¹⁴⁾
• Hypertension is a leading risk factor for ischemic heart disease, including myocardial infarction and coronary interventions.⁽¹⁵⁾
• Hypertension is a risk factor for chronic kidney disease and end-stage renal disease.^(16,17) It can both directly cause kidney disease, which is called hypertensive nephrosclerosis, and accelerate the progression of a variety of other renal diseases. The relationship between blood pressure and renal disease is stronger among blacks.

DIAGNOSTIC TEST:

SCREENING: In practice, blood pressure measurement is simple and quick.

However, at a minimum, the frequency of screening should be as follows:

• Adults 40 years or older should have their blood pressure measured at least annually
• Adults between 18 and 39 years should also be screened at least annually if they have risk factors for hypertension (e.g. obesity) or if their previously measured blood pressure was130-139/85-89 mmHg
• Adults between 18 and 39 years whose latest blood pressure was<130/80 mmHg and have no risk factors for hypertension should be screened at least every three years.

DIAGNOSIS: In patients who have an elevated screening blood pressure, the diagnosis of hypertension should be confirmed using out-of-office blood pressure measurement, preferably ambulatory blood pressure monitoring (ABPM). Home blood pressure monitoring is an acceptable alternative to ABPM if ABPM is not possible. This approach is consistent with recommendations from the United State Preventive Services Task Force (USPSTF) and the Canadian Hypertension Education Program (CHEP).^(18,19)

Evaluation: Once it has been determined that the patient has persistent hypertension, an evaluation should be performed to ascertain the following information:

• To determine the extent of target-organ damageand / or established cardiovascular disease.
• To assess other cardiovascular risk factors.
• To identify lifestyle factors that could potentially contribute to hypertension.
• To identify interfering substances (e.g. chronic use of non-steroidal anti-inflammatory drugs, oral contraceptives) and potentially curable causes of secondary hypertension.

HISTORY: The history should search for those facts that help determine the presence of precipitating or aggravating factors, the natural course of the blood pressure, the extent of target-organ damage, and the presence of other risk factors for cardiovascular disease. The patient should also be asked about the signs and symptoms that suggest an identifiable cause of hypertension.

Important aspects of the history in the patient with hypertension⁽²⁰⁾

Duration of hypertension	Presence of other risk factors
Last known normal blood pressure	Smoking
Course of the blood pressure	Diabetes
Prior treatment of hypertension	Dyslipidemia
Drugs: types, doses, side effects	Physical inactivity
Intake of agents that may cause hypertension	Dietary history
Nonsteroidal anti-inflammatory drugs	Sodium
Estrogens	Processed foods
Adrenal steroids	Alcohol
Cocaine	Saturated fats
Sympathomimetics	Psychosocial factors
Excessive sodium	Family structure
Family history	Work status
Hypertension	Educational level
Premature cardiovascular disease or death	Sexual function
Familial diseases: pheochromocytoma, renal disease, diabetes, gout	Features of sleep apnea
Symptoms of secondary causes	Early morning headaches
Muscle weakness	Daytime somnolence
Spells of tachycardia, sweating, tremor	Loud snoring
Thinning of the skin	Erratic sleep
Flank pain
Symptoms of target-organ damage
Headaches
Transient weakness or blindness
Loss of visual acuity
Chest pain
Dyspnea
Claudication

PHYSICAL EXAMINATION: The main goals on the physical examination are to evaluate for signs of end-organ damage (such as retinopathy) and for evidence of a cause of identifiable hypertension.

The various pulses should be palpated, and the abdomen should be auscultated for a renal artery bruit. The presence of an upper-abdominal bruit with a diastolic component that lateralizes toward one side is highly suggestive of renal artery stenosis.

LABORATORY TESTING: The procedures that should be routinely performed to evaluate for underlying causes (and signs of end-organ damage), as well as cardiovascular risk, are:⁽²¹⁾

• Blood chemistries including electrolytes, glucose, and creatinine, An estimated glomerular filtration rate (eGFR) should be determined.
• Lipid profile. Most hypertensive patients will have hyperlipidemia or sufficiently elevated cardiovascular risk to indicate statin therapy.^(22,23)
• Urinalysis to detect hematuria and analbumin / creatinine ratio to estimate albumin excretion.
• Electrocardiogram (ECG).

TESTS THAT ARE OCCASIONALLY PERFORMED: Additional tests may be indicated in certain settings. These include:

ECHOCARDIOGRAPHY: Routine echocardiographic evaluation of hypertensive patients is not recommended, unless there are specific indications, such as clinically evident heart failure, or if left ventricular dysfunction or coronary artery disease is suspected.⁽²⁴⁾ Echocardiography is a more sensitive method to detect left ventricular hypertrophy than the ECG. In patients suspected of having coronary artery disease, stress echocardiography (rather than standard echocardiography) may be preferred.⁽²⁵⁾

SERUM URIC ACID: Hyperuricemia has been found to be a precursor and possible pathogenetic factor for hypertension.⁽²⁶⁾ It is not known whether the presence of hyperuricemia or its treatment will influence the management of hypertension.

PLASMA RENIN ACTIVITY: Although the plasma renin activity (PRA) may provide prognostic information,⁽²⁷⁾ the test is usually performed only in patients with possible low-renin forms of hypertension, such as primary mineralocorticoid excess. The PRA may provide guidance in the evaluation and treatment of resistant hypertension.^(28,29)

WORKUP FOR RENOVASCULAR HYPERTENSION: Additional testing for renovascular disease is indicated only in patients in whom the history is suggestive (mentioned below):

• An acute elevation in serum creatinine of at least 30% after administration of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB)
• Moderate to severe hypertension in a patient with diffuse atherosclerosis, a unilateral small kidney, or asymmetry in renal size of more than 1.5 cm that cannot be explained by another reason
• Moderate to severe hypertension in patients with recurrent episodes of flash pulmonary edema
• Onset of stage II hypertension after age 55 years
• Systolic or diastolic abdominal bruit (not very sensitive)

ALBUMINURIA: In patients with hypertension, moderately increased albuminuria (formerly, microalbuminuria) is associated with an increased incidence of cardiovascular disease. The value of measuring albumin excretion in patients with primary hypertension without diabetes is being increasingly advocated to assess cardiovascular risk; however, it does not have value as a screening tool for nephropathy in non-diabetic patients with hypertension.^(30,31)

PATIENT SELECTION FOR TREATMENT:

All patients should undergo appropriate lifestyle (non-pharmacologic) modification. In the absence of evidence for hypertensive target-organ damage, the following decisions about antihypertensive medications are generally not made until there has been an adequate trial of non-pharmacologic therapy. However, if there is evidence for target-organ damage, decisions on antihypertensive medications may be warranted earlier.

• In the absence of end-organ damage, a patient should not be labeled as having hypertension unless the blood pressure is persistently elevated afterthree to six visits over a several-month period.
• Antihypertensive medications should generally be begun if the systolic pressure is persistently ≥140 mmHg (in patients younger than 60 years)and / or the diastolic pressure is persistently ≥90 mmHg in the office and at home, despite attempted non-pharmacologic therapy. The same applies to patients 60 to 79 years, although such patients are somewhat more likely to develop side effects from therapy. In patients 80 years and older, antihypertensive medications should generally be started if the systolic pressure is persistently ≥150 mmHg and / or the diastolic pressure is persistently ≥90 mmHg.

THERAPY CONSIDERATION:

Starting with two drugs may be considered in patients with a baseline blood pressure more than 20/10 mmHg above goal. This strategy may increase the likelihood that target blood pressures are achieved in a reasonable time period, but should be used cautiously in patients at increased risk for orthostatic hypotension (such as diabetics and the elderly).

In some patients with proteinuric chronic kidney disease or known cardiovascular disease, antihypertensive therapy may be indicated when the systolic pressure is persistently above 130 mmHg and / or the diastolic pressure is above 80 mmHg. The benefit of such blood pressure lowering in patients with chronic kidney disease is probably limited to patients excreting more than 0.5 to 1 g of protein per day.

In a number of conditions (e.g. heart failure, post-myocardial infarction), antihypertensive drugs are given to improve survival, independent of the blood pressure.

TREATMENT OPTIONS:

NON-PHARMACOLOGIC THERAPY: Treatment of hypertension should involve non-pharmacologic therapy (also called lifestyle modification) alone or in concert with antihypertensive drug therapy:⁽³²⁾

• Dietary salt restriction: Reduce sodium intake to no more than 100 mmol/d (2.4 g sodium or 6 g sodium chloride; range of approximate SBP reduction, 2-8 mm Hg).⁽³³⁾
• Weight loss: Weight loss in overweight or obese individuals can lead to a significant fall in blood pressure independent of exercise. The decline in blood pressure induced by weight loss can also occur in the absence of dietary sodium restriction,⁽³⁴⁾ but even modest sodium restriction may produce an additive antihypertensive effect.⁽³⁵⁾ The weight loss-induced decline in blood pressure generally ranges from 0.5 to 2 mmHg for every 1 kg of weight lost, or about 1 mmHg for every 1 pound lost.⁽³⁶⁾
• Dietary Approaches to Stop Hypertension (DASH) diet: The DASH dietary pattern is high in vegetables, fruits, low-fat dairy products, whole grains, poultry, fish, and nuts; and low in sweets, sugar-sweetened beverages, and red meats. The DASH dietary pattern is consequently rich in potassium, magnesium, calcium, protein, and fiber, but low in saturated fat, total fat, and cholesterol.
• Exercise: Aerobic exercise, and possibly resistance training, can decrease systolic and diastolic pressure by, on average, 4 to 6 mmHg and 3 mmHg, respectively, independent of weight loss.
• Limited alcohol intake: Women who consume two or more alcoholic beverages per day and men who have three or more drinks per day have a significantly increased incidence of hypertension compared with nondrinkers;^(37,38) this effect is dose related and is most prominent when intake exceeds five drinks per day. On the other hand, decreasing alcohol intake in individuals who drink excessively significantly lowers blood pressure. Moderate alcohol use (one drink per day for women and one to two drinks per day for men) has a limited effect on blood pressure, associated with a modest decrease in cardiovascular risk as compared with no alcohol consumption.
• Patient education: Patient education has been demonstrated to result in improved blood pressure control.⁽³⁹⁾ In addition to education of patients by their clinicians, blood pressure control may be improved when patients with hypertension hear the personal stories of their peers with hypertension.⁽⁴⁰⁾

PHARMACOLOGIC THERAPY:

GENERAL EFFICACY: Recommendations for the use of specific classes of antihypertensive medications are based upon clinical trial evidence of decreased cardiovascular risk, blood pressure-lowering efficacy, safety, and tolerability. Most patients with hypertension will require more than one blood pressure medication to reach goal blood pressure. Having multiple available classes of blood pressure medication permits clinicians to individualize therapy based upon individual patient characteristics and preferences.

INITIAL MONOTHERAPY IN UNCOMPLICATED HYPERTENSION: In the absence of a specific indication, there are four main classes of drugs that are recommended for use as initial monotherapy:

• Thiazide diuretics
• Long-acting calcium channel blockers (most often a dihydropyridine such asamlodipine)
• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBs)

Most guidelines and recommendations, including those made by panel members from JNC 8 and European Society of Hypertension (ESH) / European Society of Cardiology (ESC), support the use of any of these classes as initial therapy in many patients.

However, a thiazide diuretic or long-acting calcium channel blocker should be used as initial monotherapy in black patients, and an ACE inhibitor or ARB should be used for initial monotherapy in patients who have diabetic nephropathy or non-diabetic chronic kidney disease complicated by proteinuria.

Beta blockers are no longer recommended as initial monotherapy in the absence of a specific (compelling) indication for their use, such as ischemic heart disease or heart failure with decreased ejection fraction.^(41,42)

COMBINATION THERAPY: In most cases, single-agent therapy will not adequately control blood pressure, particularly in those whose blood pressure is more than 20 / 10 mmHg above goal. Combination therapy with drugs from different classes has a substantially greater blood pressure-lowering effect than doubling the dose of a single agent.⁽⁴³⁾ When more than one agent is needed to control the blood pressure, therapy with a long-acting ACE inhibitor or ARB in concert with a long-acting dihydropyridine calcium channel blocker is recommended. Combination of an ACE inhibitor or ARB with a thiazide diuretic can also be used but may be less beneficial. ACE inhibitors and ARBs should not be used together.

GOAL BLOOD PRESSURE: After antihypertensive therapy is initiated, patients should be reevaluated and therapy should be increased every two to four weeks until adequate blood pressure control is achieved. Once blood pressure control is achieved, patients should be reevaluated every three to six months to ensure maintenance of control.

DISCONTINUING THERAPY: Some patients with stage 1 hypertension are well controlled, often on a single medication. After a period of years, the question arises as to whether antihypertensive therapy can be gradually diminished or even discontinued.

After discontinuation of treatment, between 5 and 55 percent of patients remain normotensive for at least one to two years;⁽⁴⁴⁾ a larger fraction of patients do well with a decrease in the number and / or dose of medications taken.^(45,46)

More gradual tapering of drug dose is indicated in well-controlled patients taking multiple drugs.⁽⁴⁷⁾

Abrupt cessation of therapy with a short-acting beta blocker (such as propranolol) or the short-acting alpha-2 agonist, clonidine, can lead to a potentially fatal withdrawal syndrome. Gradual discontinuation of these agents over a period of weeks should prevent this problem.

GOALS OF TREATMENT:

1. Reduce cardiovascular and renal morbidity and mortality.
2. Obtain target BP goals of <140 / 90 mmHg or <130 / 80 mmHg with diabetes or renal disease.

GUIDELINES:

To review “2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults” - Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8), please click on the following link

http://jama.jamanetwork.com/article.aspx?articleid=1791497CONSULTATION AND COUNSELLING

Encourage patients to keep an up-to-date record of their blood pressure numbers. Explain that knowing their blood pressure numbers is important, even when they’re feeling fine. If their blood pressure is normal, they can work with their health care team to keep it that way. If their blood pressure is too high, treatment may help prevent damage to their body’s organs.

Make sure patients understand the concept of high blood pressure (HBP). Educate patients on systolic / diastolic pressure and what constitutes a normal blood pressure reading.

Point out that if they’re being treated for HBP and have repeat readings in the normal range, their blood pressure is under control, but they still have the condition. Counsel patients to continue seeing their physician and adhere to their treatment plan to keep their HBP under control.

Explain the role lifestyle changes such as a healthy diet, exercise, salt reduction, and smoking cessation can play in reducing HBP. For patients taking HBP medicines, reinforce the importance of staying on their medicines.

OFFER PATIENTS THE FOLLOWING TIPS:

• Take all the HBP medications your physician prescribes. Know the names and doses of the medications and how to take them. If you have questions about your medicines, talk to your pharmacist or physician.
• Make sure you refill your medications before they run out. Take your medications exactly as prescribed—don’t skip days or cut tablets in half.
• If you’re having adverse effects from your medications, inform your pharmacist and talk with your physician. He or she may need to adjust the doses or prescribe other medications. You shouldn’t decide on your own to stop taking your medications.
• Be aware of possible drug interactions with Over the counter (OTC) medicines. Some OTC products note on the label not to take if you have HBP. When in doubt, ask your pharmacist for guidance.

PRECAUTIONS:

Offer patients the following preventions:

• Eat healthy foods: Eat a healthy diet. Try the Dietary Approaches to Stop Hypertension (DASH) diet, which emphasizes fruits, vegetables, whole grains, poultry, fish and low-fat dairy foods. Get plenty of potassium, which can help prevent and control high blood pressure. Eat less saturated fat and trans fat.
• Decrease the salt in your diet: A lower sodium level, 1,500 milligrams (mg) a day is appropriate for people 51 years of age or older, and individuals of any age who are black or who have hypertension, diabetes or chronic kidney disease. Otherwise healthy people can aim for 2,300 mg a day or less.
• Maintain a healthy weight: Keeping a healthy weight, or losing weight if you're overweight or obese, can help you control your high blood pressure and lower your risk of related health problems. If you're overweight, losing even 5 pounds (2.3 kilograms) can lower your blood pressure.
• Increase physical activity: Regular physical activity can help lower your blood pressure, manage stress, reduce your risk of several health problems and keep your weight under control.
• Limit alcohol: Even if you're healthy, alcohol can raise your blood pressure. If you choose to drink alcohol, do so in moderation.
• Don't smoke: Tobacco injures blood vessel walls and speeds up the process of hardening of the arteries.
• Manage stress: Reduce stress as much as possible. Practice healthy coping techniques, such as muscle relaxation, deep breathing or meditation. Getting regular physical activity and plenty of sleep can help, too.
• Monitor your blood pressure at home: Home blood pressure monitoring can help you keep closer tabs on your blood pressure, show if medication is working, and even alert you and your doctor to potential complications. Home blood pressure monitoring isn't a substitute for visits to your doctor, and home blood pressure monitors may have some limitations. Even if you get normal readings, don't stop or change your medications or alter your diet without talking to your doctor first. If your blood pressure is under control, you may be able to make fewer visits to your doctor if you monitor your blood pressure at home.
• Practice relaxation or slow, deep breathing: Practice taking deep, slow breaths to help relax.

REFERENCES:

1. Kannel WB. Blood pressure as a cardiovascular risk factor.J Am Med Assoc. 1996;275(20):1571–1576.
2. Sarafidis PA, Li S, Chen SC, et al. Hypertension awareness, treatment, and control in chronic kidney disease.Am J Med. 2008;121(4):332–340
3. Shah SM, Luby S, Rahbar M, Khan AW, McCormick JB. Hypertension and its Determinants amongAdults in High Mountain Villages of the NorthernAreas of Pakistan. J Hum Hypertens 2001;15(2):107-12
4. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension. 2003 Dec. 42(6):1206-52.
5. Gandhi SK, Powers JC, Nomeir AM, Fowle K, Kitzman DW, Rankin KM, et al. The pathogenesis of acute pulmonary edema associated with hypertension.N Engl J Med. 2001 Jan 4. 344(1):17-22
6. Harrison DG, Guzik TJ, Lob HE, et al. Inflammation, immunity, and hypertension. Hypertension. 2011 Feb. 57(2):132-40.
7. Guzik TJ, Hoch NE, Brown KA, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007 Oct 1. 204(10):2449-60.
8. Madhur MS, Lob HE, McCann LA, et al. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010 Feb. 55(2):500-7.
9. Hamer M, Steptoe A. Cortisol responses to mental stress and incident hypertension in healthy men and women.J Clin Endocrinol Metab. 2012 Jan. 97(1):E29-34
10. Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation 2000; 102:470.
11. Vakili BA, Okin PM, Devereux RB. Prognostic implications of left ventricular hypertrophy. Am Heart J 2001; 141:334.
12. Levy D, Larson MG, Vasan RS, et al. The progression from hypertension to congestive heart failure. JAMA 1996; 275:1557.
13. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997; 350:757.
14. Thrift AG, McNeil JJ, Forbes A, Donnan GA. Risk factors for cerebral hemorrhage in the era of well-controlled hypertension. Melbourne Risk Factor Study (MERFS) Group. Stroke 1996; 27:2020.
15. Wilson PW. Established risk factors and coronary artery disease: the Framingham Study. Am J Hypertens 1994; 7:7S.
16. Coresh J, Wei GL, McQuillan G, et al. Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med 2001; 161:1207.
17. Hsu CY, McCulloch CE, Darbinian J, et al. Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease. Arch Intern Med 2005; 165:923.
18. Siu AL, U.S. Preventive Services Task Force. Screening for high blood pressure in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2015; 163:778.
19. Daskalopoulou SS, Rabi DM, Zarnke KB, et al. The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 2015; 31:549.
20. https://www.uptodate.com
21. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289:2560.
22. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63:2889.
23. Egan BM, Li J, Qanungo S, Wolfman TE. Blood pressure and cholesterol control in hypertensive hypercholesterolemic patients: national health and nutrition examination surveys 1988-2010. Circulation 2013; 128:29.
24. Dasgupta K, Quinn RR, Zarnke KB, et al. The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 2014; 30:485.
25. Senior R, Monaghan M, Becher H, et al. Stress echocardiography for the diagnosis and risk stratification of patients with suspected or known coronary artery disease: a critical appraisal. Supported by the British Society of Echocardiography. Heart 2005; 91:427.
26. Forman JP, Choi H, Curhan GC. Uric acid and insulin sensitivity and risk of incident hypertension. Arch Intern Med 2009; 169:155.
27. Laragh J. Laragh's lessons in pathophysiology and clinical pearls for treating hypertension. Am J Hypertens 2001; 14:603.
28. Egan BM, Basile JN, Rehman SU, et al. Plasma Renin test-guided drug treatment algorithm for correcting patients with treated but uncontrolled hypertension: a randomized controlled trial. Am J Hypertens 2009; 22:792.
29. Egan BM, Laken MA, Sutherland SE, et al. Aldosterone Antagonists or Renin-Guided Therapy for Treatment-Resistant Hypertension: A Comparative Effectiveness Pilot Study in Primary Care. Am J Hypertens 2016; 29:976.
30. Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009; 27:2121.
31. Bakris GL, Molitch M. Microalbuminuria as a risk predictor in diabetes: the continuing saga. Diabetes Care 2014; 37:867.
32. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63:2960.
33. Whelton PK, Appel LJ, Sacco RL, Anderson CA, Antman EM, Campbell N, et al. Sodium, Blood Pressure, and Cardiovascular Disease: Further Evidence Supporting the American Heart Association Sodium Reduction Recommendations.Circulation. 2012 Nov 2
34. Tuck ML, Sowers J, Dornfeld L, et al. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med 1981; 304:930.
35. Whelton PK, Appel LJ, Espeland MA, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group. JAMA 1998; 279:839.
36. Stevens VJ, Corrigan SA, Obarzanek E, et al. Weight loss intervention in phase 1 of the Trials of Hypertension Prevention. The TOHP Collaborative Research Group. Arch Intern Med 1993; 153:849.
37. Forman JP, Stampfer MJ, Curhan GC. Diet and lifestyle risk factors associated with incident hypertension in women. JAMA 2009; 302:401.
38. Ascherio A, Rimm EB, Giovannucci EL, et al. A prospective study of nutritional factors and hypertension among US men. Circulation 1992; 86:1475.
39. Roumie CL, Elasy TA, Greevy R, et al. Improving blood pressure control through provider education, provider alerts, and patient education: a cluster randomized trial. Ann Intern Med 2006; 145:165.
40. Houston TK, Allison JJ, Sussman M, et al. Culturally appropriate storytelling to improve blood pressure: a randomized trial. Ann Intern Med 2011; 154:77.
41. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311:507.
42. Webb AJ, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet 2010; 375:906.
43. Wald DS, Law M, Morris JK, et al. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med 2009; 122:290.
44. Schmieder RE, Rockstroh JK, Messerli FH. Antihypertensive therapy. To stop or not to stop? JAMA 1991; 265:1566.
45. Nelson MR, Reid CM, Krum H, et al. Short-term predictors of maintenance of normotension after withdrawal of antihypertensive drugs in the second Australian National Blood Pressure Study (ANBP2). Am J Hypertens 2003; 16:39.
46. Freis ED, Thomas JR, Fisher SG, et al. Effects of reduction in drugs or dosage after long-term control of systemic hypertension. Am J Cardiol 1989; 63:702.
47. Finnerty FA Jr. Stepped-down therapy versus intermittent therapy in systemic hypertension. Am J Cardiol 1990; 66:1373.