Arterial Hypertension

Overview

Systemic arterial hypertension is the leading modifiable risk factor for all-cause morbidity and death globally, and it is linked to an elevated risk of cardiovascular disease (CVD). Fewer than half of persons with hypertension are aware of their illness, and many more are aware but untreated or improperly managed, despite the fact that good hypertension therapy decreases the worldwide burden of disease and mortality.

The cause of hypertension is complicated by the interaction of environmental and pathophysiological variables affecting many systems, as well as hereditary predisposition. Accurate standardized blood pressure (BP) measurement, assessment of patients' predicted risk of atherosclerotic CVD, evidence of target organ damage, detection of secondary causes of hypertension, and presence of comorbidities, including CVD and kidney disease, are all part of the evaluation of hypertensive patients.

Arterial hypertension definition 

Systemic arterial hypertension (also known as hypertension) is defined by persistently high blood pressure (BP) in the systemic arteries. BP is generally represented as the ratio of systolic BP (the pressure exerted on the artery walls when the heart contracts) to diastolic BP (the pressure when the heart relaxes(

The blood pressure thresholds that characterize hypertension vary depending on the technique of measurement. Hypertension can be caused by a variety of factors. The majority of patients (90–95%) have primary hypertension with a complex gene-environment etiology.

Hypertension is the most common preventable risk factor for cardiovascular disease (CVD, which includes :

• Coronary heart disease,
• Heart failure
• Stroke,
• Myocardial infarction, 
• Atrial fibrillation, and 
• Chronic kidney disease (CKD), 
• Cognitive impairment, and 
• The leading single contributor to all-cause death and disability worldwide. 

The link between blood pressure and the increased risk of CVD is graded and continuous, beginning as low as 115/75 mmHg, well within the normotensive range. Successful hypertension prevention and treatment are critical in lowering illness load and enhancing lifespan in the world's population. In the treatment of hypertension

Epidemiology

According to the World Health Organization, high blood pressure is the primary cause of 54 percent of strokes and 47 percent of instances of ischemic heart disease, placing it among the leading risk factors for cardiovascular morbidity and death. The decline in stroke incidence over the last few decades can be attributed in significant part to lower blood pressure.

Globally, 3.5 billion persons have non-optimal systolic blood pressure values (that is, >110–115 mmHg), and 874 million adults have systolic blood pressure readings of 140 mmHg or more. As a result, one out of every four individuals has hypertension. Between 1990 and 2015, the total worldwide number of healthy life years lost to non-optimal BP increased by 43%, owing to population growth, population aging, and a 10% increase in the age-standardized prevalence of hypertension.

According to the Global Burden of Disease study, non-optimal BP remains the most significant single risk factor contributing to the global burden of disease and global all-cause mortality, accounting for 9.4 million deaths and 212 million lost healthy life years (8.5 percent of the global total) each year.

Pathophysiology

BP regulation

BP is determined by various cardiovascular system factors, including blood volume and cardiac output (the quantity of blood pumped by the heart per minute), as well as arterial tone balance, which is regulated by both intravascular volume and neurohumoral systems.

The renin-angiotensin-aldosterone system (RAAS), the involvement of natriuretic peptides and the endothelium, the sympathetic nervous system (SNS), and the immune system all play a part in maintaining physiological blood pressure levels. Malfunction or disruption of BP regulatory elements in any of these systems can result in increases in mean BP, BP variability, or both over time, resulting in target organ damage and CVD consequences.

The causes of hypertension are complicated and have a hereditary basis. Primary hypertension is caused by a variety of genes; some allelic variations of numerous genes are connected to an elevated risk of developing primary hypertension and are virtually always associated with a positive family history.

This genetic tendency, combined with a variety of environmental variables such as high Na+ intake, poor sleep quality or sleep apnea, excessive alcohol use, and high mental stress, all contribute to the development of hypertension. Finally, the likelihood of getting hypertension increases with age due to increasing stiffness of the arterial vasculature caused by, among other things, slowly emerging alterations in vascular collagen and increases in atherosclerosis.

Immunological variables can also play a significant role, particularly in the context of viral or rheumatological disorders such as rheumatoid arthritis. The mosaic hypothesis of hypertension describes the diverse biology of the disease.

The RAAS regulates blood pressure by mediating Na+ retention, pressure natriuresis (the mechanism by which increases in renal perfusion pressure (the gradient between renal arterial and venous blood pressure) lead to decreased Na+ reabsorption and increased Na+ excretion), salt sensitivity, vasoconstriction, endothelial dysfunction, and vascular injury, and it is involved in the pathogenesis of hypertension.

The RAAS is present at the cellular level in many organs, but its most important role is to help regulate pressure-volume homeostasis in the kidney, where it maintains perfusion in volume depleted states (that is, when extracellular fluid volume is reduced due to sodium and fluid loss) and suppresses perfusion in volume expanded (fluid overload) conditions.

Renin and its precursor pro-renin are generated and stored in the kidney's juxtaglomerular cells before being released in response to various stimuli. Renin's primary job is to cleave angiotensinogen to produce angiotensin I. Angiotensin-converting enzyme (ACE) cleaves angiotensin I to create angiotensin II, which is central to the RAAS's pathogenic involvement in hypertension.

Diagnosis

Because essential or primary hypertension is frequently asymptomatic, all individuals should have their blood pressure monitored at routine office visits. Repeated blood pressure measures in a clinical office environment are most typically used to diagnose hypertension. Accurate BP measurement and recording are required to classify BP levels, determine BP-related CVD risk, and guide management.

Since 2010, methods for measuring out-of-office blood pressure have been widely used to aid hypertension diagnosis and therapy. These include home blood pressure monitoring and ambulatory blood pressure monitoring. The measuring of blood pressure at regular intervals by an individual at home or anywhere outside of the clinic environment is referred to as BP monitoring. BP monitoring is measuring and recording blood pressure at regular intervals (generally every 20–30 minutes), usually over a 24-hour period, and as people go about their everyday activities.

The capacity to assess BP outside of the office has allowed for the discovery of unique BP phenotypes, such as white coat or isolated clinic hypertension and masked or isolated ambulatory hypertension. White coat hypertension is distinguished by increased office blood pressure but normal ambulatory BP monitoring or Home blood pressure monitoring readings.

The examination of a hypertensive patient necessitates more than just a diagnosis of high blood pressure. It should also include an evaluation of the CVD risk, target organ damage, and concomitant clinical diseases that may impact the BP or associated target organ damage, as well as detection of secondary hypertension-like characteristics.

Some of these investigations are regular tests that must be performed on all patients, while others are only performed on certain patient groups identified by history, clinical examination, and routine testing. A single gene mutation explains the pathophysiology of hypertension in uncommon hereditary types of hypertension.

 A small percentage of individuals have a potentially reversible cause of hypertension, and a correct diagnosis might result in a cure or a significant improvement in blood pressure control with a decrease in CVD risk. As a result, it is reasonable to undertake a basic secondary hypertension screening in all patients. The clinical history, physical examination, and regular laboratory tests are used in the screening.

Secondary hypertension should be explored in situations of abrupt hypertension worsening, poor BP response to pharmacological therapy, or significant target organ damage that is out of proportion to the length and severity of hypertension.

Signs suggestive of secondary hypertension

• Symtoms of Cushing syndrome
• Enlarged kidneys (polycystic kidney(
• Abdominal murmurs (renovascular hypertension(
• Precordial murmurs (aortic coarctation, aortic disease(

Signs of target organ damage

• Brain: motor or sensory deficit
• Retina: hypertensive retinopathy
• Heart: atrial fibrillation, arrhythmias, and peripheral edema
• Peripheral arteries: absent, reduced or asymmetrical pulses 
• Carotid arteries: murmurs

Laboratory investigations in the diagnosis of hypertension

Routine tests

• Haemoglobin and haematocrit
• Fasting plasma glucose
• Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol
• Fasting serum triglycerides
• Serum potassium and sodium
• Serum uric acid
• Serum creatinine
• Estimated glomerular filtration rate (eGFR)
• Urine analysis including a test for microalbuminuria
• 12-lead EKG

Screening

Despite clear evidence that hypertension is a significant controllable CVD risk factor, research from throughout the world demonstrate that a considerable number of people with hypertension are either uninformed of their high blood pressure or are aware but not being treated or are being treated insufficiently. As a result, there is a strong case for screening middle-aged or younger people in order to diagnose and treat more hypertensive individuals.

The UK has made the most serious attempt by a healthcare system to improve the diagnostic aspects of hypertension, based on the pay-for-performance principle, that is, to provide incentives to general practitioners (primary care physicians) for the appropriate diagnosis and treatment of chronic diseases, including hypertension.

Early studies indicated that this campaign was connected with greater BP monitoring and improved BP management, but a subsequent report indicated that this was not a persistent improvement.

Prevention

The connection between blood pressure and the risk of CVD emphasizes the significance of treating hypertension, especially when it is severe. Furthermore, it emphasizes the significance of efforts to lower BP-related CVD risk in persons with higher-than-normal BP (average systolic BP 120–129 mmHg) but below the hypertension threshold. Reducing blood pressure in people with high normal blood pressure (referred to as raised blood pressure in the 2017 US recommendations) has the potential to immediately reduce CVD risk and to prevent or at least slow the age-related propensity for individuals to acquire hypertension.

Most nations have a significant propensity for blood pressure, particularly systolic blood pressure, and the incidence of hypertension to rise gradually from infancy until late in life. However, studies in isolated societies with little contact with the outside world show that high blood pressure is not an inevitable result of aging and that the rise in blood pressure associated with local migration by members of isolated societies is related to dietary changes, decreased physical activity, and alcohol consumption. These studies highlight the rationality of efforts to avoid high blood pressure in contexts where an age-related rise in blood pressure is widespread. 

Management

BP treatment thresholds and targets

Until 2015, most guidelines advised a target blood pressure of 140/90 mmHg for most individuals and 150/90 mmHg for elderly patients over the age of 60 or 80. Patients with a history of stroke were not eligible. Participants were randomly assigned to either a regular systolic blood pressure target of 140 mmHg or an intensive systolic blood pressure target of 120 mmHg.

Lifestyle changes

Nonpharmacological therapies have been demonstrated to be beneficial in decreasing blood pressure and avoiding hypertension. Weight loss, reduced Na+ intake, increased potassium intake, increased physical activity, reduced alcohol use, and diets like the Dietary Approaches to Stop Hypertension (DASH) diet that include numerous factors that favorably influence BP are the most effective therapies.

The DASH diet is highly beneficial when paired with other effective BP-lowering strategies, such as limiting dietary salt intake. Individuals can best adopt these therapies through lifestyle changes. Even minor changes in a person's lifestyle might be beneficial.

Websites from government agencies and professional societies offer useful recommendations for changing one's lifestyle and monitoring one's blood pressure. Careful blood pressure monitoring is required since the favorable benefits of lifestyle changes are contingent on the intervention being maintained.

Physical activity

Regular physical exercise lowers blood pressure in hypertensive people. Endurance exercise lowers blood pressure more in those with hypertension than in people with normal blood pressure. A narrative analysis of 27 randomized clinical studies in hypertensive people found that regular medium- to high-intensity aerobic exercise decreased blood pressure by an average of 11/5 mmHg.

Sessions lasting 40–60 minutes and completed at least three times per week had the greatest effect on blood pressure. Three studies of isometric exercise (strength training) in hypertensive persons revealed a BP decrease comparable to that generated by aerobic exercise.

Weight Loss

Excess adiposity normally elevates blood pressure in susceptible individuals, and patients with hypertension who are also obese require more antihypertensive drugs to regulate their blood pressure and are more likely to be resistant to therapy. The reaction, however, varies greatly across individuals. Despite the fact that lifestyle therapies such as hypocaloric diets and physical activity are routinely suggested for patients with obesity and hypertension, typical weight reduction is modest and the majority of individuals regain weight.

Pharmacological interventions

In three randomized controlled studies including people with high normal blood pressure, low-dose pharmacological treatment was demonstrated to be beneficial in decreasing BP and avoiding hypertension. The Brazilian center for prevention evaluated low-dose long-acting thiazide-like diuretic chlorthalidone in conjunction with the potassium sparing drug amiloride against placebo.

Treatment with a low-dose chlorthalidone and amiloride combination resulted in both a drop in blood pressure and hypertension prevention, as well as a reduction in left ventricular mass. A pharmacological intervention is simpler to adopt and sustain than a lifestyle modification intervention, yet it is reasonable to be hesitant to propose a lifetime of pharmaceutical therapy for hypertension prevention.

Low-dose pharmacotherapy should be considered only for people who are at high risk of developing hypertension despite vigorous efforts to decrease blood pressure with one or more nonpharmacological therapies.

Antihypertensive pharmacotherapy has changed over several decades as a result of the introduction of numerous antihypertensive drug classes and large-scale outcomes studies demonstrating its advantages in terms of CVD morbidity and death. Clinicians are now confronted with a multiplicity of antihypertensive medicines from various pharmacological classes and fixed dosage combinations.

Antihypertensive pharmacotherapy often begins with first-line antihypertensive medicines, either alone or in combination. In individuals with greater levels of pretreatment BP, combination therapy may be recommended. ACE inhibitors, angiotensin II receptor blockers (also known as sartans), dihydropyridine calcium channel blockers, and thiazide diuretics are among the first-line antihypertensive drugs.

Beta-blockers are also suggested in patients with heart failure and a low left ventricular ejection fraction or who have had a heart attack, and some recommendations advocate beta-blockers as first-line antihypertensive drugs. Individual efficacy and tolerability should guide the decision. Ethnicity influences antihypertensive drug response, and calcium channel blockers and diuretics may be the first option among blacks.

Furthermore, in specific clinical situations, such as hypertension in pregnant women, other medications such as alpha-methyldopa (a central nervous system alpha adrenoreceptor agonist that inhibits the sympathetic nervous system) or labetalol (a beta adrenoreceptor blocker) are preferable, whereas some first-line antihypertensives, such as ACE inhibitors and angiotensin II receptor blockers, are contraindicated due to Antihypertensive medicine dosage in stages has been shown to reduce adherence and should be avoided wherever feasible. 

Many individuals, particularly those with severe hypertension, cannot regulate their blood pressure with monotherapy. When mixing antihypertensive medicines, it is necessary to examine if the drugs have additive or detrimental effects on blood pressure, as well as whether the patient has comorbidities that need specific treatment selections.

ACE inhibitors or angiotensin II receptor blockers, thiazide diuretics, and dihydropyridine calcium channel blockers are all additive in decreasing blood pressure and can be taken as a double or triple therapy.

Combining ACE inhibitors and angiotensin II receptor blockers, on the other hand, provides modest BP reduction while raising the risk of renal impairment and hyperkalemia (high blood potassium levels, which can lead to cardiac arrhythmias). Combining RAAS inhibitors with beta-adrenoreceptor blockers contributes modest BP reduction, although this combination is recommended in patients with acute myocardial infarction or heart failure with decreased left ventricular ejection fraction for reasons other than BP reduction.

Hypertension and obesity

Individuals with obesity should lose weight, which is especially crucial if they also have hypertension. Medications for the treatment of obesity have been created, but their approval status varies between the United States and Europe: certain treatments are only licensed in the United States (for example, lorcaserin and topiramate/phentermine), while others are only approved in Europe.

Some weight loss drugs have been shown to lower blood pressure in hypertensive individuals, however their unique pharmacological activities may mitigate the good effects of weight loss on blood pressure and CVD outcomes.

Bariatric surgery is quite successful in reducing body weight, and the risk of arterial hypertension is significantly decreased for up to five years after surgery. However, significant and sustained weight loss is required to significantly lower blood pressure after bariatric surgery, and there are no big clinical trials particularly examining the impact of weight loss drugs or bariatric surgery on hypertension control.

Conclusion 

Arterial hypertension is diagnosed when repeated readings at a doctor's office show levels of 140/90 mmHg or above. The diagnosis should be verified by 24-hour ambulatory blood pressure monitoring or home measurement. Other risk factors including end-organ damage should also be examined.

According to current European standards, the goal blood pressure for all individuals, including those with diabetes mellitus or renal failure, is 140/90 mmHg. If the medication is well tolerated, continued reduction of blood pressure with a set lower limit is suggested for the majority of patients.

Non-pharmacological treatments for high blood pressure include limiting salt in the diet, avoiding excessive alcohol use, quitting smoking, eating a balanced diet, exercising, and losing weight. Long-acting dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and thiazide-like diuretics are the first-line medications for arterial hypertension.

Mineralocorticoid-receptor blockers are useful in individuals whose blood pressure cannot be brought down to an acceptable level with first-line medications.