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Ectasia and the development of aneurysmal disease, for example, frequently occur in the aorta Chap. In addition to focal, flow-limiting stenoses, nonocclusive intimal atherosclerosis also occurs diffusely in affected arteries, as shown by intravascular imaging and postmortem studies. Atherogenesis in humans typically occurs over a period of many years, usually many decades. Growth of atherosclerotic plaques probably does not occur in a smooth, linear fashion but discontinuously, with periods of relative quiescence punctuated by periods of rapid evolution. The clinical expressions of atherosclerosis may be chronic , as in the development of stable, effort-induced angina pectoris or predictable and reproducible intermittent claudication.

Alternatively, a dramatic acute clinical event such as MI, stroke, or sudden cardiac death may first herald the presence of atherosclerosis. Other individuals may never experience clinical manifestations of arterial disease despite the presence of widespread atherosclerosis demonstrated postmortem. These early lesions most often seem to arise from focal increases in the content of lipoproteins within regions of the intima. In particular, the fraction of lipoproteins related to low-density lipoprotein LDL that bear apolipoprotein B appear causally related to Forgot Password?

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The consumption of these drinks should be discouraged. Excessive weight gain is associated with hypertension, and reducing weight towards an ideal body weight decreases BP. Weight reduction is recommended in overweight and obese hypertensive patients for control of metabolic risk factors, but weight stabilization may be a reasonable goal for many. The Prospective Studies Collaboration concluded that mortality was lowest at a body mass index BMI of approximately Weight loss should employ a multidisciplinary approach that includes dietary advice, regular exercise, and motivational counselling.

Weight loss can also be promoted by anti-obesity drugs and, to a greater degree, bariatric surgery, which appears to decrease CV risk in severely obese patients. Epidemiological studies suggest that regular aerobic physical activity may be beneficial for both the prevention and treatment of hypertension, and to lower CV risk and mortality.

A meta-analysis of RCTs, which rely on self-reported exercise and are by necessity unblinded, has shown that aerobic endurance training, dynamic resistance training, and isometric training reduce resting SBP and DBP by 3. For additional benefit in healthy adults, a gradual increase in aerobic physical activity to min a week of moderate intensity or min a week of vigorous-intensity aerobic physical activity, or an equivalent combination thereof, is recommended.

Smoking is a major risk factor for CVD and cancer. Smoking is second only to BP in contributing risk to the global burden of disease, and smoking cessation is probably the single most effective lifestyle measure for the prevention of CVD, including stroke, myocardial infarction, and PAD. Most patients will require drug therapy in addition to lifestyle measures to achieve optimal BP control. In the previous Guidelines, five major drug classes were recommended for the treatment of hypertension: ACE inhibitors, ARBs, beta-blockers, CCBs, and diuretics thiazides and thiazide-like diuretics such as chlortalidone and indapamide , based on: i proven ability to reduce BP; ii evidence from placebo-controlled studies that they reduce CV events; and iii evidence of broad equivalence on overall CV morbidity and mortality, with the conclusion that benefit from their use predominantly derives from BP lowering.

These conclusions have since been confirmed by recent meta-analyses. These Guidelines thus recommend that the same five major classes of drugs should form the basis of antihypertensive therapy. There are compelling or possible contraindications for each class of drug Table 20 and preferential use of some drugs for some conditions, as discussed below.

Coronary heart disease, clogged arteries and atherosclerosis

There is also evidence that there are differences in the persistence and discontinuation rates of the major drug classes. Other classes of drugs have been less widely studied in event-based RCTs or are known to be associated with a higher risk of adverse effects [e. These are useful additions to the antihypertensive armamentarium in patients whose BP cannot be controlled by proven combinations of the aforementioned major drug classes.

They have similar effectiveness , as each other and other major drug classes on major CV events and mortality outcomes. This result halted further research into the clinical utility of aliskiren for BP treatment. ACE inhibitors are associated with a small increased risk of angioneurotic oedema, especially in people of black African origin and, in such patients, when RAS blockers are used, an ARB may be preferred.

CCBs are widely used for the treatment of hypertension and have similar effectiveness as other major drug classes on BP, major CV events, and mortality outcomes. Though clinically a very relevant event, it is a difficult endpoint to quantify precisely, either because symptoms and signs are relatively non-specific or because oedema due to CCBs may result in misdiagnosis.

Comparison with diuretics may also be difficult because fluid loss may mask signs and symptoms of incipient heart failure rather than preventing it. CCBs have also been compared with other antihypertensive agents in HMOD-based trials, and are reported to be more effective than beta-blockers in slowing the progression of carotid atherosclerosis, and in reducing LVH and proteinuria.

CCBs are a heterogeneous class of agents. A smaller number of RCTs have compared non-dihydropyridines verapamil and diltiazem with other drugs, and meta-analyses evaluating the two subclasses vs. Diuretics have remained the cornerstone of antihypertensive treatment since their introduction in the s. Their effectiveness in preventing all types of CV morbidities and mortality has been confirmed in RCTs and meta-analyses. Chlorthalidone and indapamide have been used in a number of RCTs showing CV benefits, and these agents are more potent per milligram than hydrochlorothiazide in lowering BP, with a longer duration of action compared with hydrochlorothiazide and no evidence of a greater incidence of side effects.

Both thiazide and thiazide-like diuretics can reduce serum potassium and have a side effect profile that is less favourable than RAS blockers, which may account for their association with a higher rate of treatment discontinuation.

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Potassium may attenuate these effects, and a recent study has shown that the adverse effect of thiazides on glucose metabolism may be reduced by the addition of a potassium-sparing diuretic. In such circumstances, loop diuretics such as furosemide or torasemide should replace thiazides and thiazide-like diuretics to achieve an antihypertensive effect. RCTs and meta-analyses demonstrate that when compared with placebo, beta-blockers significantly reduce the risk of stroke, heart failure, and major CV events in hypertensive patients.

They also exhibit a somewhat less favourable side effect profile than that of RAS blockers, with a higher rate of treatment discontinuation when assessed in real-life conditions.

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  • Finally, beta-blockers are not a homogeneous class. In recent years, the use of vasodilating beta-blockers—such as labetalol, nebivolol, celiprolol, and carvedilol—has increased. Studies on nebivolol have shown that it has more favourable effects on central BP, aortic stiffness, endothelial dysfunction, etc. It has no adverse effect on the risk of new-onset diabetes and a more favourable side effect profile than classical beta-blockers, , including less adverse effects on sexual function. Bisoprolol, carvedilol, and nebivolol have been shown to improve outcomes in RCTs in heart failure; however, there are no RCTs reporting patient outcomes with these beta-blockers in hypertensive patients.

    Centrally active drugs were widely used in the earliest decades of antihypertensive treatment when other treatments were not available, but are less frequently used now, principally because of their poorer tolerability relative to the newer major classes of drugs. Antihypertensive drugs, other than the major classes already discussed above, are no longer recommended for the routine treatment of hypertension, and are primarily reserved for add-on therapy in rare cases of drug-resistant hypertension where all other treatment options have failed.

    Guidelines have generated a variety of different strategies to initiate and escalate BP-lowering medication to improve BP control rates.

    Abbreviations and acronyms

    In previous Guidelines, the emphasis was on initial use of different monotherapies, increasing their dose, or substituting for another monotherapy. However, increasing the dose of monotherapy produces little additional BP lowering and may increase the risk of adverse effects, whilst switching from one monotherapy to another is frustrating, time consuming, and often ineffective.

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    For these reasons, more recent Guidelines have increasingly focused on the stepped-care approach, initiating treatment with different monotherapies and then sequentially adding other drugs until BP control is achieved. Despite this, BP control rates have remained poor worldwide. Several reasons need to be considered to identify why the current treatment strategy has failed to achieve better BP control rates: Efficacy of pharmacological therapies.

    Are the best available treatments, in whatever combination, incapable of controlling BP in most patients? Physician or treatment inertia. Patient adherence to treatment. Evidence is accumulating that adherence is a much more important factor than previously recognised. Studies using urine or blood assays for the presence or absence of medication have shown that adherence to treatment is low. Insufficient use of combination treatment.

    BP is a multiregulated variable depending on many compensating pathways. Consequently, combinations of drugs, working through different mechanisms, are required to reduce BP in most people with hypertension. Thus, monotherapy is likely to be inadequate therapy in most patients. Complexity of current treatment strategies. There is also evidence that adherence to treatment is adversely affected by the complexity of the prescribed treatment regimen. In a recent study, adherence to treatment was strongly influenced by the number of pills that a patient was prescribed for the treatment of hypertension.

    The above considerations suggest that the most effective evidence-based treatment strategy to improve BP control is one that: i encourages the use of combination treatment in most patients, especially in the context of lower BP targets; ii enables the use of SPC therapy for most patients, to improve adherence to treatment; and iii follows a treatment algorithm that is simple, applies to all patients, and is pragmatic, with the use of SPC therapy as initial therapy for most patients, except those with BP in the high—normal range and in frail older patients see below.

    Among the large number of RCTs of antihypertensive therapy, only a few have directly compared different two-drug combinations, with systematic use of the two combinations in both arms. In other trials, treatment was initiated using monotherapy in either arm and another drug and sometimes more than one drug was added, usually in a non-randomized fashion, according to a pre-specified treatment algorithm.

    In a few trials, the design precluded the use of what might be considered optimal combinations because multiple monotherapies were being evaluated [e.


    With this caveat, Table 21 shows that a variety of drug combinations have been used in at least one active arm of placebo-controlled trials and have been associated with significant benefit on major CV events. In trials comparing different regimens Table 22 , all combinations have been used in a larger or smaller proportion of patients, without major differences in benefits. The only exceptions are two trials in which a large proportion of the patients received either an ARB—diuretic combination or CCB—ACE inhibitor combination, with both regimens being superior to a beta-blocker—diuretic combination in reducing CV outcomes.

    However, in six other trials with seven comparisons , beta-blockers followed by diuretics or diuretics followed by beta-blockers were not associated with a significantly different risk of any CV outcome, , , , — and the beta-blocker diuretic combination was significantly more effective than placebo in three trials.

    Major drug combinations used in trials of antihypertensive treatment in a stepped approach or as a randomized combination combinations vs.

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    Based on the results of outcome RCTs and recent meta-analyses, and evidence of BP-lowering effectiveness, all five major drug classes can, in principle, be combined with one another, except for ACE inhibitors and ARBs, whose concomitant use may lead to no additional benefit but increased adverse effects and is thus discouraged. These combinations are now widely available in a single pill and in a range of doses, facilitating simplification of treatment, flexible prescribing, and uptitration from lower to higher doses.

    These combinations will also limit potential adverse effects associated with diuretic or CCB monotherapy, reducing the risk of hypokalaemia due to diuretics and reducing the prevalence of peripheral oedema due to CCBs. These combinations also ensure that the RAS is inhibited as part of the treatment strategy, which is an important consideration for many patient groups e.