Low-dose atorvastatin reduces ambulatory blood pressure in patients with mild hypertension and hypercholesterolaemia: a double-blind, randomized, placebo-controlled study.

Among several beneficial cardiovascular actions of statins, experimental studies have suggested that statins may also induce a mild blood pressure (BP) reduction. However, clinical data were controversial and the potential hypotensive statin effect remains uncertain. This study aimed to investigate the effect of atorvastatin on ambulatory BP in patients with mild hypertension and hypercholesterolaemia. A total of 50 patients with mild hypertension and hypercholesterolaemia participated in this double-blind, randomized, placebo-controlled study. Patients were randomized to either 10 mg atorvastatin or placebo for 26 weeks. Background antihypertensive treatment, if any, remained unchanged during follow-up. At baseline and study-end (26 weeks), ambulatory BP monitoring and blood sampling for determination of standard biochemical and safety parameters were performed in all participants. BP loads were defined as the percentage of BP measurements exceeding the hypertension threshold of 140/90 mm Hg for daytime and 125/75 mm Hg nighttime period. Atorvastatin significantly reduced 24-h systolic and diastolic BP (DBP; median (range)) as compared with placebo (-5.0 (-21.0, 4.0) vs +1.0 (-6.0, 7.0) mm Hg, P<0.001 and -3.0 (-16.0, 2.0) vs +0.1 (-7, 4) mm Hg, P<0.01, respectively). Reductions in systolic and DBP loads during follow-up were also evident in the atorvastatin, but not in the placebo group. BP-lowering effects of atorvastatin were consistent in both daytime and nighttime periods. This study shows a mild, but consistent throughout the 24-h period BP-lowering effect of atorvastatin in patients with mild hypertension and hypercholesterolaemia. This beneficial effect of atorvastatin on BP may represent another pathway through which this drug class provides cardiovascular risk reduction.

24-hour intraocular pressure and blood pressure levels with latanoprost/timolol fixed combination versus timolol.

PURPOSE: To evaluate 24-hr intraocular pressure (IOP) and blood pressure (BP) with timolol or latanoprost/timolol fixed combination (LTFC). METHODS: Patients with primary open-angle glaucoma or ocular hypertension with normal blood pressure were randomized to LTFC, dosed each evening, or timolol dosed twice daily in a cross-over design for 8 weeks and the opposite medicine for 8 weeks. IOP was measured at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours in the sitting position with Goldmann applanation tonometry and BP monitoring every 30 min while awake and every hour while asleep at the end of each 8-week treatment period. RESULTS: Twenty-nine patients had a 24-hr baseline IOP of 26.3 +/- 2.5 mmHg, systolic BP (SBP) of 121.4 +/- 12.4 mmHg, diastolic BP (DBP) 72.9 +/- 7.1 mmHg, and ocular perfusion pressure (OPP) of 33.9 +/- 5.7 mmHg. No statistical differences were found between untreated and treated 24-hr SBP, DBP, mean BP (MBP), heart rate, or nocturnal BP dipping status with either medication. LTFC lowered IOP more at each timepoint compared to timolol (difference between treatments 2.7 mmHg, p = 0.0002). CONCLUSIONS: Neither timolol or evening-dosed LTFC reduced SBP, DBP, MBP, OPP, or increased nocturnal dipping. LTFC was more effective than timolol in decreasing IOP.

Insulin sensitivity increase after calcium supplementation and change in intraplatelet calcium and sodium-hydrogen exchange in hypertensive patients with Type 2 diabetes.

AIMS/HYPOTHESIS: To investigate the effect of oral calcium (Ca(2+)) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca(2+) ([Ca(2+)](i)) and the transmembrane sodium-hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension. PATIENTS AND METHODS: In this parallel randomized controlled single-blinded trial, 31 patients were allocated to receive either 1500 mg of Ca(2+) orally, daily (n = 15) or no treatment (n = 16) for 8 weeks. At baseline and at the end of the 8-week period insulin sensitivity, [Ca(2+)](i) and the first isoform of NHE (NHE-1) activity were measured. RESULTS: At the end of the study, subjects who received Ca(2+) supplementation showed higher insulin sensitivity (Delta M-value 0.32 +/- 0.5 mmol/min P < 0.05) and lower [Ca(2+)](i) (125.0 +/- 24.7 to 80.4 +/- 10.6 nmol/l, P < 0.05, mean +/- sem) and NHE-1 activity (79.5 +/- 10.0 to 52.1 +/- 6.4 mmol Na/l red cell/h, P < 0.05). None of the above parameters were changed in the control group. Simple regression analysis demonstrated the change in [Ca(2+)](i) significantly determined insulin sensitivity change (beta = -0.36, P < 0.05). CONCLUSIONS/INTERPRETATION: Oral Ca(2+) supplementation improves insulin sensitivity in patients with Type 2 diabetes and hypertension. These changes are likely to be mediated by changes in intracellular ionic Ca(2+). NHE-1 activity was also reduced after Ca(2+) supplementation but its role in insulin sensitivity requires further investigation.

Cost-effectiveness of losartan in diabetic nephropathy: a Greek perspective.

BACKGROUND: Diabetic nephropathy is the primary cause of end-stage renal disease (ESRD), which involves substantial economic burden. The primary objective of this study was to estimate the potential effect of losartan on the costs associated with ESRD in patients with diabetic nephropathy in a Greek setting. A secondary aim was to approximate the direct health care cost of renal replacement therapy (RRT) in Greece. METHODS: A cost-effectiveness analysis was performed to compare losartan with placebo in patients with type 2 diabetes and nephropathy. Clinical data were derived from the RENAAL study. All costs were calculated from the perspective of the Greek social insurance system, in 2003 euros. Future costs were discounted at 3%. The time horizon was 3.5 years. Extensive sensitivity analyses were performed. RESULTS: The reduction in the number of ESRD days over 3.5 years in patients treated with losartan reduced ESRD-related costs by 3,056.54 euros, resulting in net cost savings of 1,665.43 euros per patient. Net cost savings increase thereafter, increasing to 2,686.48 euros per patient over a period of 4.0 years. The results were robust under a wide range of plausible assumptions. The weighted mean daily cost of RRT was estimated at 90.97 euros per patient. The total economic burden of RRT for the year 2003 has been estimated at 304.773 million euros. CONCLUSIONS: This study demonstrated that treatment of patients with diabetic nephropathy in Greece with losartan is cost-effective, as it leads to important savings for the social insurance system by slowing the progression to ESRD.

Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley's indices in patients with hypertension and type II diabetes.

The aim of this study was to evaluate the validity and reliability of homeostasis model assessment-insulin resistance (HOMA-IR) index, its reciprocal (1/HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and McAuley's index in hypertensive diabetic patients. In 78 patients with hypertension and type II diabetes glucose, insulin and triglyceride levels were determined after a 12-h fast to calculate these indices, and insulin sensitivity (IS) was measured with the hyperinsulinemic euglycemic clamp technique. Two weeks later, subjects had again their glucose, insulin and triglycerides measured. Simple and multiple linear regression analysis were applied to assess the validity of these indices compared to clamp IS and coefficients of variation between the two visits were estimated to assess their reproducibility. HOMA-IR index was strongly and inversely correlated with the basic IS clamp index, the M-value (r=-0.572, P<0.001), M-value normalized with subjects' body weight or fat-free mass and every other clamp-derived index. 1/HOMA-IR and QUICKI indices were positively correlated with the M-value (r=0.342, P<0.05 and r=0.456, P<0.01, respectively) and the rest clamp indices. McAuley's index generally presented less strong correlations (r=0.317, P<0.05 with M-value). In multivariate analysis, HOMA-IR was the best fit of clamp-derived IS. Coefficients of variation between the two visits were 23.5% for HOMA-IR, 19.2% for 1/HOMA-IR, 7.8% for QUICKI and 15.1% for McAuley's index. In conclusion, HOMA-IR, 1/HOMA-IR and QUICKI are valid estimates of clamp-derived IS in patients with hypertension and type II diabetes, whereas the validity of McAuley's index needs further evaluation. QUICKI displayed better reproducibility than the other indices.

Increased natriuretic ability and hypotensive effect during short-term high calcium intake in essential hypertension.

The present study has investigated whether an increased natriuresis could account for the hypotensive effect of a high calcium diet which has been reported by others. A calcium supplement (equivalent to 1 g of elemental calcium) was given for 5 days to 18 patients with essential hypertension in a randomized single-blind, placebo-controlled, cross-over trial. In 15 of the patients, 2 liters of isotonic saline were infused intravenously over 4 h during the last day of each test period and hourly urine collections were taken. Calcium supplementation produced a mild but significant hypercalcemia as well as increased urinary calcium excretion. Body weight and systolic blood pressure decreased significantly. The blood pressure decrease was indirectly related to the pretreatment plasma renin activity (r = -0.61, p less than 0.01). Urinary sodium excretion increased during calcium diet (80 mmol/day negative balance, p less than 0.01). During saline infusion under calcium supplementation the urine volume, osmolality and sodium excretion were significantly higher compared with placebo. The changes in urinary sodium excretion correlated positively with the changes in urinary calcium excretion (r = 0.68, p less than 0.01) in patients given the high calcium diet, when infused with saline. We conclude that calcium supplementation induces a considerable sodium loss in the urine which is very likely to result in the hypotensive effect.

The effects of canrenoate K on corticosteroid biosynthesis in nephrectomized dogs.

There is evidence from in vitro experiments that spironolactone not only antagonises the peripheral effects of aldosterone but also inhibits the production of corticosteroids by the adrenals. However relevant data from clinical studies are contradictory probably because spironolactone action on the kidneys also activates other mechanisms, such as renin secretion and potassium retention, which are potent stimulants of the adrenal cortex and thus tend to compensate for the inhibition. To determine the inhibitory effect of spironolactone on the adrenals in isolation, three groups of nephrectomized dogs were studied. Steroidogenesis was stimulated either by angiotensin II, potassium, or ACTH infusion. Potassium canrenoate was administered i.v. bolus at the beginning of the experiment. All the groups showed a similar marked decrease in plasma renin activity (PRA). Plasma aldosterone and cortisol were stimulated by the appropriate stimulus but their increase was blunted after the canrenoate K administration. The altered response between the subgroups was statistically significant (P less than 0.05). Plasma progesterone increased after the administration of canrenoate K. The response difference between the respective subgroups was again statistically significant (P less than 0.05). Canrenoate K was rapidly eliminated from the systemic circulation. These data indicate that canrenoate K causes a partial inhibition of aldosterone and cortisol stimulated secretion but augments the plasma levels of the precursor progesterone, as would be expected following inhibition of specific steps of corticosteroid biosynthesis.