Journal of hypertension. Supplement : official journal of the International Society of Hypertension最新文献

The early detection of cardiac organ damage in clinical practice is primordial for cardiovascular risk profiling of patients with hypertension. In this respect the determination of microalbuminuria is very appealing because it increasingly appears to be the most cost-effective means to identify cardiovascular and renal complications. Considering the treatment of patients with target organ damage, blockers of the renin-angiotensin system have a key position as they are very effective in regressing left ventricular hypertrophy, lowering urinary albumin excretion and delaying the progression of nephropathy. In high-risk patients with atherosclerosis, the use of a blocker of the renin-angiotensin system is also appealing, and it appears increasingly judicious to combine such a blocker with a calcium antagonist whenever required to control blood pressure.

Inhibition of the renin-angiotensin system (RAS) either with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) has been shown to be beneficial for cardiorenal protection. The combination of both is an exciting prospect and pathophysiologically plausible. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study provides evidence that dual blockade does not further reduce cardiovascular events or worsen renal outcomes. However, in patients with existing diabetic nephropathy, a trend towards a better outcome was observed. Therefore, combination of ARBs and ACEIs could be an alternative for selected patients, but not a standard approach in the management of chronic kidney disease. The benefits of dual blockade on hard renal endpoints remain to be shown.

Prevention of diabetes represents an important therapeutic goal in current cardiovascular risk reduction strategies. Blockade of the renin-angiotensin system has been shown to markedly reduce the incidence of new-onset diabetes in different patient populations. Recent results from three large clinical endpoint trials with the angiotensin-II receptor blocker telmisartan regarding new-onset diabetes, atrial fibrillation, and left ventricular hypotrophy will be discussed.

Cardiovascular disease is responsible for 70% of all mortality among patients with type 2 diabetes and is also a major contributor to diabetes-related healthcare costs. The ADVANCE trial clearly demonstrated that a simple and easily applicable pharmacological strategy based on perindopril/indapamide fixed combination could substantially reduce total and cardiovascular mortality (-14% and -18%, respectively). The observed benefits were largely caused by a substantial decrease in systolic blood pressure (SBP), confirming the need to have ambitious therapeutic goals in such high-risk patients. This point is of importance because most of the patients included in the trial were being treated for hypertension, and baseline brachial SBP and diastolic blood pressure at inclusion were very close to normal. Previous mechanistic studies have highlighted the positive effect of perindopril/indapamide fixed combination on large artery function as well as on microvascular structure. For example, in the REASON trial, in patients treated with perindopril/indapamide, the decrease in central aortic SBP, which closely correlated with the decrease in left ventricular hypertrophy, reflected a significant improvement in large artery function and a changing pattern in both peripheral reflection coefficients and structural arteriolar network. These data are supported by those from other studies, which show increases in coronary blood flow reserve with perindopril/indapamide treatment. In conclusion, normalization of SBP, pulse pressure, arterial function and myocardial perfusion, a haemodynamic profile known to improve survival in the hypertensive populations at high cardiovascular risk, seems to be more easily achieved when a strategy based on the perindopril/indapamide combination is applied.

The need to prevent the development of renal damage and its associated increase in cardiovascular risk in patients with type 2 diabetes is well established. Early intervention to maintain strict blood pressure control and to prevent the development of microalbuminuria is mandatory and will constitute the primary aim of intervention in patients with diabetes and also in prediabetes, characterized by the presence of cardiometabolic risk. If microalbuminuria is already present, similar blood pressure control and normalized urinary albumin excretion are required. If diabetic nephropathy is established, similar blood pressure and albumin targets must be achieved. In this regard, data from the ADVANCE study suggest that the combination of perindopril and indapamide can greatly help clinicians to achieve these targets. This combination on top of standard treatment significantly reduced the risk of renal events by 21% (P < 0.0001), the progression of albuminuria by 22% (P < 0.0001), and increased the regression of albuminuria by 16% (P = 0.002). Furthermore, the rate of renal events decreased log-linearly with decreasing follow-up blood pressure, down to systolic blood pressure below 110 mmHg. According to the ADVANCE results, treatment with the perindopril/indapamide fixed combination on top of contemporary cardiovascular care prevents one renal event in 20 patients with type 2 diabetes treated over 5 years. Evidence of renal protection is added to the reduction in total and cardiovascular mortality in the main ADVANCE trial.

Difficulties in achieving a reduction in morbidity and mortality in patients with diabetes are a result of the complexity of the disease and its intertwined relationship with hypertension and renal impairment. In the recently published Action in Diabetes and Vascular disease: PreterAx and DiamicroN-MR Controlled Evaluation (ADVANCE) trial, treatment of patients with diabetes with the fixed combination perindopril/indapamide on top of background treatments provided clinically and statistically significant reductions in blood pressure (from 145/81 to 136/73 mmHg), all-cause mortality (-14%), cardiovascular mortality (-18%), major cardiovascular events (-9%), renal events (-21%) and new-onset microalbuminuria (-21%) when compared with placebo. As the ADVANCE trial included both hypertensive and normotensive patients, its results suggest that systematically treating all patients with diabetes with perindopril/indapamide, independently of their baseline blood pressure, may have significant long-term value that can be explained partly by the reversal of end-organ damage to the kidney and the heart. Considering that patients with both hypertension and diabetes are characterized by generalized macro- and microvascular disease, the results of the ADVANCE trial, taken together with results of other perindopril/indapamide hypertension studies, support a broad use of perindopril/indapamide treatment for the long-term improvement of prognosis in hypertensive patients as well as in patients with diabetes.

Objectives: To evaluate among individuals with diabetes whether major microvascular and macrovascular events are reduced by: (1) blood pressure lowering with a perindopril/indapamide combination compared with placebo; (2) intensive glucose control (targeting a haemoglobin A1c level of < or =6.5%) with a gliclazide MR-based regimen, compared with usual care.

Methods: Participants with diabetes aged 55 years and older with at least one additional vascular risk factor were randomly assigned, using a 2 x 2 factorial design, to additional blood pressure lowering versus placebo and intensive versus standard glucose control. The primary outcomes were macrovascular (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) and microvascular (new or worsening nephropathy or retinopathy) events jointly and separately.

Results: A total of 11 140 participants were randomly assigned to the blood pressure and glucose-lowering arms, which ended after 4.3 and 5.5 years, respectively. The effects of the two interventions were independent and additive on prespecified endpoints. Compared with placebo, additional blood pressure lowering of 5.6/2.2 mmHg was associated with reductions of 9% in the primary endpoint (P = 0.041), 18% in cardiovascular death (P = 0.027), 14% in total mortality (P = 0.025), and 21% in total renal events (P < 0.01). Compared with standard glucose control, intensive control (mean in-trial 0.67 percentage point reduction in haemoglobin A1c level) was associated with reductions of 10% in the primary endpoint (P = 0.013), 14% in major microvascular events (P = 0.01) and 11% in total renal events (P < 0.001).

Conclusion: Additional blood pressure lowering and intensive glucose control, as achieved in ADVANCE, produce independent benefits and, when combined, substantially reduced cardiovascular mortality and all-cause mortality and improved renal outcomes.

This white paper is an urgent call to action from an international group of physicians. The continued failure to control hypertension takes an unacceptable toll on patients, families and society and it must be addressed. Any patient with blood pressure of 140/90 mmHg or greater can be characterized as a 'challenging patient', is at significant risk, and requires persistent optimization of therapy until target blood pressure is achieved. Six key challenges in reaching this goal blood pressure are described: (1) inadequate primary prevention; (2) faulty awareness of risk; (3) lack of simplicity; (4) therapeutic inertia; (5) insufficient patient empowerment; and (6) unsupportive healthcare systems. This white paper identifies straightforward actions that will produce rapid improvements in the management of hypertension, with a simple aim: to treat all challenging patients effectively to goal blood pressure, preventing disability and saving lives.