Rationale for double renin-angiotensin-aldosterone system blockade.

The clinical benefits of both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) extend beyond blood pressure reduction to encompass tissue-protective effects in target organs, such as the heart, vasculature, and kidneys, that underlie the reductions in cardiovascular mortality and morbidity seen in large outcome trials. However, these effects are achieved by different mechanisms. ACE inhibitors reduce circulating and tissue angiotensin II levels and potentiate the beneficial effects of bradykinin, including generation of nitric oxide (NO). By contrast, the protective effects of ARBs are owing to the blockade of the angiotensin II type 1 (AT(1)) receptors and possibly also to the stimulation of angiotensin II type 2 (AT(2)) receptors, again resulting in NO release. In addition, some ARBs, such as telmisartan, are selective activators of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), thereby increasing insulin sensitivity. In contrast to other PPAR-gamma ligands, such as the thiazolidinediones, activation of this receptor by telmisartan does not result in weight gain. The complementary mechanisms of action of ACE inhibitors and ARBs create a rationale for combination therapy in high-risk patients. The benefits of this approach with telmisartan are being investigated in clinical trials, such as the Ongoing Telmisartan Alone in Combination with Ramipril Global Endpoint Trial (ONTARGET).

Effect of high-dose valsartan on inflammatory and lipid parameters in patients with Type 2 diabetes and hypertension.

AIMS: The present study aimed to explore the impact of the angiotensin type 1 receptor blocker valsartan (VAL) on inflammatory-/lipid-/glucose parameters in hypertensive diabetic patients with and without coronary artery disease (CAD). METHODS: This was a 16-week, randomized, double-blind, placebo-controlled two-center study with VAL 320 mg/d in 109 hypertensive diabetic patients (n=56 non-CAD; n=53 CAD). RESULTS: VAL treatment did not significantly affect serum interleukin-6 (IL-6) or tumor necrosis factor alpha (TNFalpha) levels in the overall study population but significantly reduced serum IL-6 in the subgroup with high inflammatory load at baseline (IL-6>median (2.0 ng/L), n=54: [median, ng/L]): VAL: from 3.5 to 2.4; placebo: from 3.2 to 3.5; p=0.035). VAL significantly lowered total- and LDL-cholesterol in the whole study population: [median, mg/dL]: total cholesterol: VAL: from 178 to 168; placebo: from 174 to 173, p=0.039; LDL-cholesterol: VAL: from 96 to 90, placebo: from 102 to 103, p=0.006, whereas glycemic parameters were not affected. CONCLUSIONS: The present study demonstrates significant anti-inflammatory efficacy of VAL in hypertensive diabetic patients with enhanced inflammatory burden. High-dose VAL therapy significantly lowered total- and LDL-cholesterol levels. The combined actions of cholesterol and blood pressure lowering by VAL may provide additional clinical benefits for these high-risk patients.

HYDRA: possible determinants of unsatisfactory hypertension control in German primary care patients.

The Hypertension and Diabetes Screening and Awareness (HYDRA) study is a cross-sectional point-prevalence study performed in September 2001; 45,125 primary care attendees were recruited from a representative nationwide sample of 1912 primary care practices in Germany. Around 42% of all patients presenting in these practices had hypertension (WHO definition). In approximately 70% of these patients, hypertension was diagnosed by doctors and 84% of diagnosed patients were on antihypertensive medication, but in less than 30% of treated patients was blood pressure controlled (< 140/90 mmHg). The control rate in all patients presenting with hypertension (including those patients unrecognized) was as low as 19%. The present analysis aimed to find explanations for this unsatisfactory outcome of hypertension control. The main finding was that the rate of diagnosis of hypertension is alarmingly low in young people, probably due to insufficient blood pressure screenings. The data further indicated that doctors still set their target of treatment according to outdated guidelines and that doctors still orientate their treatment primarily with regard to the diastolic pressure. These insights into the causes of unsatisfactory hypertension control may help to direct future educational programmes designed to improve hypertension management specifically to these deficits and thereby to improve control rates.