What are the general management strategies for hypertension in both high-risk patients and the general population, including dietary modifications and pharmacological interventions?

General Management of Hypertension

Blood Pressure Targets

For most adults, target blood pressure should be <140/90 mm Hg minimum, with an optimal target of 120-139 mm Hg systolic if well tolerated 1. For higher-risk patients including those with diabetes, chronic kidney disease, or established cardiovascular disease, the target is <130/80 mm Hg 2, 1. In adults ≥65 years, target SBP <130 mm Hg 3.

Initial Assessment and Diagnosis

• Confirm hypertension diagnosis using out-of-office measurements: home BP monitoring ≥135/85 mm Hg or 24-hour ambulatory BP ≥130/80 mm Hg, rather than relying solely on office readings 1.
• Perform routine investigations including urine strip test for blood and protein, serum electrolytes and creatinine, blood glucose, total:HDL cholesterol ratio, and 12-lead electrocardiograph 1.
• Assess cardiovascular risk using 10-year CVD risk calculation and screen for target organ damage, diabetes, chronic kidney disease, or established CVD 1.

Lifestyle Modifications (First-Line for All Patients)

Lifestyle modifications should be initiated simultaneously with pharmacological therapy in confirmed hypertension, not sequentially 1. The BP-lowering effects of individual lifestyle components are partially additive and enhance the efficacy of pharmacologic therapy 3.

Dietary Management

• Sodium restriction to <2g/day by eliminating excessively salty foods and limiting salt in cooking, which produces 5-10 mmHg systolic reduction with greater benefit in elderly patients 4, 1.
• Potassium supplementation through dietary sources to enhance BP reduction 3.
• Weight reduction to achieve BMI 20-25 kg/m² through reduced fat and total calorie intake; a 10 kg weight loss is associated with 6.0 mmHg systolic and 4.6 mmHg diastolic reduction 4, 1.
• DASH diet pattern, which reduces systolic and diastolic BP by 11.4 and 5.5 mmHg more than control diet 4.

Physical Activity and Alcohol

• Regular aerobic physical exercise (predominantly dynamic like brisk walking rather than isometric) designed to improve fitness, with a minimum of 30 minutes most days producing 4 mmHg systolic and 3 mmHg diastolic reduction 4, 1.
• Alcohol limitation to <21 units/week for men, <14 units/week for women 1.

Pharmacological Intervention

Initial Therapy: Combination Over Monotherapy

Start immediately with two-drug combination therapy rather than monotherapy for confirmed hypertension (BP ≥140/90 mm Hg) 1. Use fixed-dose single-pill combinations when available to improve adherence 1.

First-Line Combination Options

The preferred first-line combination is a RAS blocker (ACE inhibitor or ARB) combined with either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic 1, 3.

For Non-Black Patients:

• Start with ACE inhibitor or ARB + calcium channel blocker 2, 5.
• Alternative: ACE inhibitor or ARB + thiazide/thiazide-like diuretic 2.

For Black Patients:

• Start with calcium channel blocker + thiazide/thiazide-like diuretic, as this combination may be more effective than calcium channel blocker + ACE inhibitor/ARB 2.

Specific Drug Classes and Dosing

Thiazide/Thiazide-Like Diuretics

• Chlorthalidone 12.5-25mg daily is preferred over hydrochlorothiazide due to its longer duration of action and proven cardiovascular disease reduction 2, 3.
• Hydrochlorothiazide 25-50mg daily is an alternative if chlorthalidone is unavailable 2.

ACE Inhibitors/ARBs

• Losartan: usual starting dose 50 mg once daily, can be increased to maximum 100 mg once daily 6.
• For patients with possible intravascular depletion (e.g., on diuretic therapy), start with 25 mg 6.
• Other options include enalapril, candesartan, benazepril, or olmesartan 2, 3.

Calcium Channel Blockers

• Amlodipine 5-10mg daily is the preferred dihydropyridine calcium channel blocker 2, 3.
• Monitor for peripheral edema, which may be attenuated by adding an ACE inhibitor or ARB 2.

Stepwise Treatment Algorithm

If BP remains uncontrolled on dual therapy at optimal doses, add a third agent from the remaining class to achieve triple therapy (ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic) 2, 1.

1. Optimize doses of initial two-drug combination before adding a third agent 2, 5.
2. Add thiazide/thiazide-like diuretic as third agent if not already included, creating the evidence-based triple therapy combination targeting three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction 2.
3. Monitor serum potassium and creatinine 2-4 weeks after initiating RAS blockers or diuretics 2, 1.
4. Reassess BP within 2-4 weeks after any dose adjustment, with goal of achieving target BP within 3 months 2, 1.

Management of Resistant Hypertension

Definition and Prevalence

Resistant hypertension is defined as seated office BP >140/90 mm Hg in a patient treated with three or more antihypertensive medications at optimal doses including a diuretic, after excluding pseudoresistance 4. Approximately 50% of patients diagnosed with resistant hypertension have pseudoresistance rather than true resistant hypertension 4.

Critical Steps Before Adding Fourth Agent

1. Exclude pseudoresistance: poor BP measurement technique, white coat effect, nonadherence, and suboptimal medication choices 4.
2. Verify medication adherence, as non-adherence is the most common cause of apparent treatment resistance 2.
3. Identify interfering medications such as NSAIDs, which should be avoided or withdrawn 4.
4. Screen for secondary causes including primary aldosteronism, renal artery stenosis, obstructive sleep apnea, and pheochromocytoma 4, 7.

Diuretic Optimization

Ensure maximally tolerated doses of diuretics and optimal choice: use thiazide-like (chlorthalidone) rather than thiazide diuretics, and initiate loop diuretics for eGFR <30 ml/min/1.73m² or clinical volume overload 4.

Fourth-Line Agent

Add low-dose spironolactone 25-50mg daily as the preferred fourth-line agent in those whose serum potassium is <4.5 mmol/L and whose eGFR is >45 ml/min/1.73m² 4, 2. Spironolactone provides additional BP reductions of 20-25/10-12 mmHg when added to triple therapy 2.

Alternative fourth-line agents if spironolactone is contraindicated include amiloride, doxazosin, eplerenone, clonidine, or a beta-blocker 2.

Special Populations

High-Risk Patients

Metabolic Syndrome

• Patients with hypertension and metabolic syndrome have a high-risk profile 4.
• Treatment should include BP control as in the general population and treatment of additional risk factors based on overall cardiovascular risk 4.
• Lifestyle modifications (diet and exercise) form the foundation of metabolic syndrome treatment 4.

Inflammatory Rheumatic Diseases

• Presence of inflammatory rheumatic disease should increase cardiovascular risk by 1 step 4.
• BP should be lowered as in the general population, preferentially with RAS-inhibitors and calcium channel blockers 4.
• Avoid high doses of NSAIDs 4.

Psychiatric Diseases

• Depression has been associated with cardiovascular morbidity and mortality, emphasizing the importance of BP control 4.
• BP should be lowered as in the general population, preferentially with RAS-inhibitors and diuretics with lesser rate of pharmacological interactions under antidepressants 4.
• Use calcium channel blockers and alpha-1 blockers with care in patients with orthostatic hypotension 4.

Diabetes and Chronic Kidney Disease

• Target BP <130/80 mm Hg 2.
• For diabetic nephropathy with elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g), losartan reduces the rate of progression of nephropathy 6.
• Lowering BP to levels well below 140/90 mm Hg is needed to slow progression of renal dysfunction 8.

Left Ventricular Hypertrophy

• Start with losartan 50 mg once daily 6.
• Add hydrochlorothiazide 12.5 mg daily and/or increase losartan to 100 mg once daily, followed by increasing hydrochlorothiazide to 25 mg once daily based on BP response 6.
• Note: This benefit does not apply to Black patients 6.

Elderly Patients

• Do not withhold appropriate treatment intensification solely based on age 2.
• Target SBP <130 mm Hg in adults ≥65 years 3.
• Isolated systolic hypertension should not be considered a physiologic manifestation of normal aging and requires treatment 8.

Monitoring and Follow-Up

• See patients frequently (every 1-3 months) until BP is controlled 1.
• Achieve target BP within 3 months of treatment initiation or modification 1.
• Allow 2-4 weeks for full effect of dose adjustments before further changes 5.
• Refer to hypertension specialist if BP remains uncontrolled despite adherence to four-drug regimen including a diuretic 5.

Critical Pitfalls to Avoid

• Never use monotherapy as initial treatment for confirmed hypertension (BP ≥140/90 mm Hg) - combination therapy is recommended from the outset 1.
• Never combine two RAS blockers (ACE inhibitor + ARB) - this increases adverse events including hyperkalemia and acute kidney injury without additional cardiovascular benefit 2, 1.
• Never delay pharmacological treatment while attempting lifestyle modifications alone in confirmed hypertension - both should be initiated simultaneously 1.
• Do not add a third drug class before maximizing doses of the current two-drug regimen 2.
• Do not add beta-blocker as third agent unless there are compelling indications such as angina, post-MI, heart failure with reduced ejection fraction, or need for heart rate control 2.
• Avoid non-dihydropyridine calcium channel blockers (diltiazem or verapamil) in patients with heart failure 2.