INTRODUCTION ― Hypertension is defined as persistently elevated arterial blood pressure (BP) or usual office blood pressure of 140/90 mm Hg or higher, but recent U.S. guidelines have changed the definition to 130/80. Normal blood pressure (BP) in adults: systolic BP < 120 mmHg and diastolic < 80 mmHg. According to NICE guidelines, hypertension (HTN) can be classified to...

Prehypertension: systolic BP 120 to 139 mmHg or diastolic BP 80 to 89 mmHg.
Stage 1 HTN: systolic BP 140 to 159 mmHg or diastolic BP 90 to 99 mmHg.
Stage 2 HTN: systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg.

ETIOLOGY

Primary or essential hypertension, unknown cause (90% patients). Secondary causes (see figure 1) of hypertension (10% patients).

Image source: Manual Of Medicine

Figure 1; Causes of Secondary Hypertension.

PATHOPHYSIOLOGY

Abnormalities involving humoral (i.e., the renin–angiotensin–aldosterone system [RAAS]) or vasodepressor mechanisms, abnormal neuronal mechanisms, defects in peripheral autoregulation, and disturbances in sodium, calcium, and natriuretic hormones. Disturbance in the central nervous system (CNS), autonomic nerve fibers, adrenergic receptors, or baroreceptors. Abnormalities in renal or tissue autoregulatory processes for: sodium excretion, plasma volume and arteriolar constriction. Deficiency in synthesis of vasodilators in vascular endothelium (prostacyclin, bradykinin, nitric oxide) or excess vasoconstrictors (angiotensin II, endothelin I). High sodium intake or lack of dietary calcium.

ASSESSMENT

The asymptomatic nature of hypertension and the inherent variability in blood pressure delay the diagnosis of hypertension. Hypertension is commonly considered a “silent killer,” which can be asymptomatic, undetected, and untreated, while it silently damages the blood vessels, heart, brain, and kidneys. The principal clinical manifestations are related to end-organ damage, especially ischemic heart disease, heart failure, and stroke. Renal damage commonly is first suspected by an asymptomatic elevation in the serum creatinine level.

DIAGNOSIS

Diagnosis based on average of ≥ 2 readings taken at each of ≥ 2 visits (see Table 1).

Differential diagnosis. Primary, White coat hypertension; BP cuff is too small. Secondary, see Etiology section.

Table 1;

Classification of Blood Pressure in Adults.

Laboratory tests. Blood urea nitrogen (BUN)/serum creatinine, lipid panel, fasting blood glucose, serum electrolytes, spot urine albumin-to-creatinine ratio and hemoglobin and hematocrit. Laboratory tests for secondary hypertension ARE plasma norepinephrine and urinary metanephrine levels, plasma and urinary aldosterone concentrations, plasma renin activity, captopril stimulation test, renal vein renin and renal artery angiography. AND do 12-lead electrocardiogram (ECG).

MANAGEMENT

Short-term pharmacologic therapy with a low-dose angiotensin receptor blocker (ARB) may prevent the conversion from prehypertension to hypertension, BUT blood pressure quickly rises again if the ARB is discontinued. Thus, lifelong prescription medication is the cornerstone of effective therapy for primary hypertension, with lifestyle modification serving as a very important adjunct but not as an alternative. The objective is to use anti-hypertensive drug therapy to reduce the blood pressure and associated metabolic abnormalities sufficiently to reduce cardiovascular disease risk, with benefits that are proportional to the reduction in blood pressure achieved, without compromising the patient’s quality of life.

In practice. Multidrug regimens with 2 or 3 medications of different drug classes are almost always required to achieve recommended blood pressure goals. Low-dose drug combinations exert synergistic beneficial effects while minimizing dose-dependent side effects. For most patients with hypertension, moderate or intensive statin therapy is indicated as part of a comprehensive cardiovascular risk-reduction strategy. For further information see note, "Optimization of lipids in cardiovascular patients (focus on statin dose instead of LDL levels)".

For example, the addition of 10 mg of rosuvastatin daily lowers this residual risk in patients who have intermediate cardiovascular risk and mildly elevated blood pressure and who are treated with a mild blood pressure-lowering regimen (candesartan 16 mg daily and hydrochlorothiazide 12.5 mg daily).

Lifestyle modifications. Lose weight if overweight (target BMI < 25). Limit alcohol intake to 1 oz of ethanol per day (< 2 drinks/day) in men or 0.5 oz (< 1 drink/day) in women. Perform regular aerobic exercise (at least 30 min/day on most days). Reduce Na intake to < 100 mmol/day (< 1.5 g of Na /day). Maintain adequate dietary K (> 3500 mg/day) intake in patients with normal kidney function AND stop smoking.

Pharmacological therapy. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults, goals of treatment are as follows:

For adults with confirmed hypertension and known cardiovascular disease (CVD) or 10-yr atherosclerotic cardiovascular disease (ASCVD) event risk of 10% or higher, a BP target of less than 130/80 mm Hg is recommended.

For adults with confirmed hypertension without additional markers of increased CVD risk, a BP target of less than 130/80 mm Hg may be reasonable.

In addition, initiation of therapy recommendations by using of BP-lowering medication is recommended for primary prevention of CVD in adults with no history of CVD and with an estimated 10-yr ASCVD risk <10% and stage 2 hypertension.

Use of BP-lowering medications is recommended for secondary prevention of recurrent CVD events in patients with clinical CVD and for primary prevention in adults with an estimated 10-yr ASCVD risk of 10% or higher and stage 1 hypertension. Initiate antihypertensive drug therapy with two first-line agents of different classes for adults with stage 2 hypertension and BP more than 20/10 mm Hg higher than their target. It is reasonable to initiate therapy with a single agent for adults with stage 1 hypertension and a goal less than 130/80 mm Hg. Patients with diabetes mellitus and chronic kidney disease are considered high risk.

Anti-hypertensive medication selection. In the general non-black population, preferred initial agents are thiazide-type diuretics, angiotensin-converting enzyme inhibitors (ACEI), calcium channel blockers (CCBs), or angiotensin receptor blockers (ARBs). ACEI or ARBs are preferred initial agents in diabetics and those with chronic kidney disease (CKD) in this population. Preferred initial agents in the black population (including diabetics) are thiazide-type diuretics or CCBs. When selecting drugs, try to give once per day dosages to improve compliance. Also consider the cost of the medication, metabolic and subjective side effects, and drug-drug interactions. The major advantages and limitations of each class of drugs are described as follows (see Table 2)..

Table (2). Antihypertensive medications
Medication	Advantages	Disadvantages
ACE inhibitors	First-line therapy for patients with left ventricular dysfunction, helpful in prevention of diabetic renal disease; effective in decreasing LVH, and remodeling.	Dry cough is a frequent side effect (5% to 20% of patients); hyperkalemia may occur in patients with diabetes or severe renal insufficiency; hypotension may occur in volume-depleted patients; increased risk of renal failure in patients with renal artery stenosis; contraindicated in pregnancy.
ARBs	Well tolerated, favorable impact on quality of life; useful in patients unable to tolerate ACE inhibitors because of persistent cough and in CHF and diabetic patients; single daily dose. An episode of renal insufficiency with ACE inhibitors does not rule out future therapy with an ARB unless high-grade bilateral renal artery stenosis exists.	Hypotension may occur in volume-depleted patients; hyperkalemia; risk of renal failure in renal artery stenosis; contraindicated in pregnancy.
Thiazide diuretics	Inexpensive, once-daily dosing. Useful in edematous states, CHF, chronic renal disease, elderly patients (decreased incidence of hip fractures in elderly patients).	Significant adverse metabolic effects (hypokalemia), increased risk of cardiac arrhythmias, sexual dysfunction, gout flares, possible adverse effects on lipids and glucose levels.
Calcium antagonists	Helpful in hypertensive patients with ischemic heart disease. Generally favorable effect on quality of life; can be used in patients with bronchospastic disorders, renal disease, peripheral vascular disease, metabolic disorders, and salt sensitivity. CCBs BP-lowering effect is independent of Na + intake.	Diltiazem and verapamil should be avoided in patients with CHF due to systolic dysfunction because of their negative inotropic effects; pedal edema may occur with nifedipine and amlodipine; constipation can be severe in elderly patients receiving verapamil. CCB-related edema is positional in nature, it improves with lying position; additional strategies include switching CCB classes, reducing dosage, giving the medication later in the day, and adding a venodilator (nitrates, an ACE, or an ARB); diuretics may improve edema, but at the expense of a reduction in plasma volume.
Beta-blockers	Ideal in hypertensive patients with ischemic heart disease or status post myocardial infarction (MI); favored in hyperkinetic, young patients (resting tachycardia, wide pulse pressure, hyperdynamic heart) and stable CHF patients.	Adverse effect on quality of life (increased incidence of fatigue, depression, impotence), bronchospasm, hypoglycemia, peripheral vascular disease, adverse effects on lipids, masking of signs and symptoms of hypoglycemia in diabetics.
Alpha-adrenergic blockers	No adverse effect on blood lipids or insulin sensitivity; helpful in benign prostatic hypertrophy.	Postural hypotension, sedation; syncope can be avoided by giving an initial low dose at bedtime. Generally considered third- or fourth-line agent.
Central alpha-antagonists	Oral clonidine mainstay of therapy for hypertensive urgencies because of the ease of administration and relative safety. Transdermal clonidine: useful in management of labile HTN, the hospitalized patient who cannot take medications by mouth, and patients subject to early-morning BP surges. At equivalent doses, transdermal clonidine is more apt to precipitate salt and water retention than is the case with oral clonidine. Dose beyond 0.4 mg causes fatigue, sedation, dry mouth, salt and water retention, and rebound HTN upon abrupt termination of the medication.
Combined alpha- and beta-adrenergic receptor blockers	Labetalol, nebivolol, and carvedilol: Use is reserved to treat complicated hypertensive patients when an antihypertensive effect beyond beta-blockade is sought. IV labetalol is used for hypertensive emergencies. Carvedilol is shown to have less adverse effect on glycemic control than metoprolol and to reduce urinary protein excretion in hypertensive diabetic patients.
Direct-acting smooth muscle relaxant (Hydralazine)	Beneficial in black patients when used with isosorbide dinitrate.	May lead to reflex tachycardia, worsening ischemia (best used with nitrates), at higher doses or with renal failure can lead to a reversible drug-induced lupus.
Renin inhibitors (Aliskiren)	Generally well tolerated; once-daily dosing; can be used alone or in combination with other antihypertensive agents (avoid combining with ACEI or ARBs given increase of hyperkalemia).	Contraindicated in pregnancy; should not be used in patients with impaired renal function; excessive cost; paucity of cardiovascular outcomes data showing benefit.

REFERENCES

James, P.A., Oparil, S., Carter, B.L., Cushman, W.C., Dennison-Himmelfarb, C., Handler, J., Lackland, D.T., LeFevre, M.L., MacKenzie, T.D., Ogedegbe, O., Smith, S.C., Svetkey, L.P., Taler, S.J., Townsend, R.R., Wright, J.T., Narva, A.S. and Ortiz, E. (2014). 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, [online] 311(5), pp.507–20. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24352797

James, P.A., Oparil, S., Carter, B.L., Cushman, W.C., Dennison-Himmelfarb, C., Handler, J., Lackland, D.T., LeFevre, M.L., MacKenzie, T.D., Ogedegbe, O., Smith, S.C., Svetkey, L.P., Taler, S.J., Townsend, R.R., Wright, J.T., Narva, A.S. and Ortiz, E. (2014). 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, [online] 311(5), pp.507–20. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24352797
‌Ferri, F.F. (2020). Ferri’s clinical advisor 2020 : 5 books in 1. Philadelphia, Pa: Elsevier
NICE (2019). Overview | Hypertension in adults: diagnosis and management. Available at: https://www.nice.org.uk/guidance/ng136

Overview of hypertension