Hypertension

Abstract

Systemic arterial hypertension is the most important modifiable risk factor for all-cause morbidity and mortality worldwide and is associated with an increased risk of cardiovascular disease (CVD). Fewer than half of those with hypertension are aware of their condition, and many others are aware but not treated or inadequately treated, although successful treatment of hypertension reduces the global burden of disease and mortality. The aetiology of hypertension involves the complex interplay of environmental and pathophysiological factors that affect multiple systems, as well as genetic predisposition. The evaluation of patients with hypertension includes accurate standardized blood pressure (BP) measurement, assessment of the patients' predicted risk of atherosclerotic CVD and evidence of target-organ damage, and detection of secondary causes of hypertension and presence of comorbidities (such as CVD and kidney disease). Lifestyle changes, including dietary modifications and increased physical activity, are effective in lowering BP and preventing hypertension and its CVD sequelae. Pharmacological therapy is very effective in lowering BP and in preventing CVD outcomes in most patients; first-line antihypertensive medications include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, dihydropyridine calcium-channel blockers and thiazide diuretics.

Figure 1.. Association between systolic blood pressure and coronary heart disease mortality

Relationship of systolic BP to subsequent risk of coronary heart disease mortality in >340,000 US men 35–57 years of age at the beginning of the study followed-up for an average 11.6 years. A | Distribution of the incidence of coronary heart disease mortality, adjusted for age, race, total serum cholesterol level, cigarettes smoked per day, use of medication for diabetes, and income. Individuals with the highest BPs were at greatest risk for CVD mortality. B | Prevalence of coronary heart disease mortality; only a minority of the sample was exposed to the high risk associated with hypertension (≥140 mmHg for systolic BP, as per office BP measurement). However, a much larger number of them, who had BP in the non-hypertensive range, were exposed to the more modest but still important increases in CVD risk. C | Estimation of the percent of excess coronary heart disease deaths occurring in each category of systolic BP, using those with a systolic BP <110 mm Hg as the reference group. About two-thirds of the overall burden of BP-related CHD mortality occurred in men who had a systolic BP ≥140 mmHg (25% of the sample). However, about two-thirds of the remaining disease burden could be attributed to the approximately 20% of adults who had a systolic BP in the high-normal range (systolic BP 130–139 mmHg). Data from Ref..

Figure 2.. The main neuroendocrine systems involved in the regulation of blood pressure.

Neurohumoral, immune and organ systems involved in the maintenance of blood pressure. BP: Blood pressure, RAAS: renin-angiotensin-aldosterone system.

Figure 3.. Role of the renin-angiotensin-aldosterone system in the regulation of blood pressure

Decreased renal afferent perfusion pressure, reduced Na⁺ delivery to the macula densa (an area lining the wall of the distal convoluted tubule in correspondence of the glomerulus), activation of renal sympathetic nerves (via β₁ adrenergic receptor stimulation) and a variety of vasodilators, including prostaglandin E2, stimulate the release of renin. Angiotensin II activates the AT1 receptor, triggering smooth muscle cell contraction, systemic vasoconstriction, increased renovascular resistance and decreased renal medullary blood flow, a mediator of salt sensitivity. Stimulation of the AT2 receptor has opposite effects, resulting in vasodilation, natriuresis and anti-proliferative actions. Cross-transplantation studies using wild-type mice and mice lacking the AT1 receptor have shown that both systemic and renal actions of angiotensin II are relevant to physiologic BP regulation, but that the detrimental effects of angiotensin II in hypertension are mediated mainly via the kidney^,. ACE inhibitors and AT1 receptor antagonists have been shown to increase Ang-(1–7) levels in plasma and urine of normotensive animals and enhance renal ACE2 activity.. Studies in rodents and humans with non-diabetic kidney disease suggest that upregulation of ACE2 may delay progression of kidney disease.

Figure 4. Pathways affected in single gene, Mendelian hypertension and hypotension syndromes

Some inherited diseases can affect the renal-angiotensin-aldosterone system pathways and, therefore, the blood pressure; hypertensive disorders are listed in red boxes and hypotensive disorders in green boxes. MR, mineralocorticoid receptor; GRA, glucocorticoid-remediable aldosteronism; PHA1, pseudohypoaldosteronism, type-1; AME, apparent mineralocorticoid excess; SLC12A1, solute carrier family 12 member 1; SLC12A3, solute carrier family 12 member 3; CLCNKB, chloride channel protein ClC-Kb; KCNJ, inward rectifier potassium channel; ECaC, epithelial calcium channel; ENaC; epithelial Na channel; WNK1, Serine/threonine-protein kinase WNK1; HSD11B1, corticosteroid 11-beta-dehydrogenase isozyme 1; CYP21A2, steroid 21-hydroxylase; CYP17A1, steroid 17-alpha-hydroxylase/17,20 lyase; CYP11B1, cytochrome P450 11B1, mitochondrial. Modified from Ref

Figure 5.. Algorithm for the management of hypertension

Reproduced from ref.