Changes in Kidney Function in a Population With Essential Hypertension in Real Life Settings.

INTRODUCTION: Hypertension has been identified as one of the commonest modifiable determinants for chronic kidney disease progression. A variety of antihypertensive drugs are available and their effect on kidney function has been investigated by a large number of randomized controlled trials. Observational studies, although scarcely been used, outpatient can reflect everyday practice, where drug exposures vary over time, and may provide an alternative for detecting longitudinal changes in kidney function. MATERIALS AND METHODS: We applied mixed model repeated measures analysis to investigate the effect of antihypertensive drug categories and their combinations on kidney function change over time in a cohort of 779 patients with essential hypertension, using the data from a Greek hypertension outpatient clinic. Antihypertensive drugs were grouped in 5 categories. Their effect was evaluated and their combinations with and without renin-angiotensin-system inhibitors (RASI) to each other. In addition, the combination of RASI with calcium channel blockers (CCBs) was studied. RESULTS: Diuretics, RASI, CCBs, and beta-blockers had a significant renoprotective and blood pressure lowering effect. Combinations with RASI had a smaller beneficial effect on kidney function compared to CCBs (0.75 mL/min/1.73 m2 per year of drug use versus 0.97 mL/min/1.73 m2). There was no additional effect when combining RASI with CCBs. However, the lowering effect on systolic blood pressure was greater (-0.83 mm Hg per year of drug use, P < .001). CONCLUSIONS: RASI were found to have a smaller, although significant, renoprotective effect. There was no additional effect on kidney function when combining RASI with CCBs.

Effects of low-dose atorvastatin on arterial stiffness and central aortic pressure augmentation in patients with hypertension and hypercholesterolemia.

BACKGROUND: Experimental and clinical data suggest that statins exert anti-inflammatory and antiproliferative actions on vasculature beyond their lipid-lowering properties. Whether these pleiotropic effects of statins translate into a beneficial effect on arterial stiffness is not clear. This study aimed to evaluate the potential effects of low-dose atorvastatin treatment on arterial stiffness and central arterial pressure waveforms in patients with mild hypertension and hypercholesterolemia. METHODS: In a double-blind, randomized, placebo-controlled fashion, 50 hypertensive and hypercholesterolemic patients were allocated to receive 10 mg of atorvastatin or placebo for 26 weeks. Arterial stiffness was assessed by aortic pulse-wave velocity (PWV) using a Sphygmocor device. Central arterial pressure waveform parameters were estimated by radial artery applanation tonometry. Heart rate-adjusted augmentation index (AIx(75)) was used as measure of wave reflections. RESULTS: At study end, aortic PWV (9.0 ± 1.5 vs. 10.9 ± 2.6 m/sec; P < 0.001) and AIx(75) (24.9% ± 9.7% vs 28.8% ± 11.8%; P < 0.001) were significantly lower in the atorvastatin group than that placebo group. Furthermore, decreases in central aortic systolic blood pressure and pulse pressure were evident at study-end with atorvastatin but not with placebo (130 ± 8 vs. 138 ± 6 mm Hg, P < 0.001; 48 ± 7 vs. 53 ± 6 mm Hg, P < 0.05, respectively). Atorvastatin-induced reductions in aortic PWV during follow-up showed significant associations with changes in AIx(75) and central aortic systolic blood pressure and pulse pressure. CONCLUSIONS: This study shows that low-dose atorvastatin treatment improves arterial stiffness and exerts a reduction on central aortic pressures. These effects may represent a potential mechanism of cardiovascular risk reduction observed with statin use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Database Identifier Number: NCT01126684.

Beneficial effects of oral magnesium supplementation on insulin sensitivity and serum lipid profile.

BACKGROUND: Epidemiological studies have associated low dietary Mg2+ intake with insulin resistance (IR) and increased risk for metabolic syndrome; however, the effect of Mg2+ supplementation on IR has not been adequately investigated. This study aimed to investigate the effects of oral Mg2+ supplementation on insulin sensitivity (IS) and serum lipids.
MATERIAL/METHODS: Forty-eight patients with mild uncomplicated hypertension participated in the study. Among them, 24 subjects were assigned to 600 mg of pidolate Mg2+ daily in addition to lifestyle recommendations for a 12-week period, and another 24 age- and sex-matched controls were only given lifestyle recommendations. At baseline and study-end, blood sampling for determination of fasting glucose and insulin levels, serum lipids and other standard laboratory tests, as well as an oral glucose tolerance test (OGTT) for estimation of IS indices, were performed in all subjects.
RESULTS: In the Mg2+ supplementation group the OGTT-derived IS indices of Stumvoll, Matsuda and Cedercholm in were increased between baseline baseline and study-end. In contrast, none of these parameters were changed in the control group. Reductions in total cholesterol, LDL-cholesterol and triglyceride levels, along with a parallel increase in HDL-cholesterol levels, were evident at study-end in the intervention group, but not in the control group.
CONCLUSIONS: This study suggests that oral Mg2+ supplementation improves IS and lipid profile in mildly hypertensive patients. These potential beneficial effects of Mg2+ on associated metabolic factors could be helpful for patients with hypertension in terms of overall cardiovascular risk reduction.

Oral calcium supplementation ambulatory blood pressure and relation to changes in intracellular ions and sodium-hydrogen exchange.

BACKGROUND: Calcium (Ca2+) supplementation has been shown paradoxically to reduce intracellular Ca2+ and induce vascular relaxation. The aim of the study was to assess 24-h blood pressure (BP) change after Ca2+ supplementation and to investigate its relation to changes in intracellular ions and the activity of the first isoform of sodium-hydrogen exchange (NHE-1) in subjects with hypertension and type 2 diabetes. METHODS: This parallel, randomized controlled, single-blinded trial, consisted of 31 patients with type 2 diabetes, and hypertension who were allocated to receive 1,500 mg of Ca2+ per day (n = 15) or no treatment (n = 16) for 8 weeks. RESULTS: In the Ca2+ group a decrease of 1.7 +/- 2.7 mm Hg (mean +/- SE) P = 0.52 for mean 24-h systolic BP (SBP) and 2.1 +/- 1.5 mm Hg, P = 0.19 for mean 24-h diastolic BP (DBP) was recorded. Whereas in the control group an increase of 1.4 +/- 2.7 mm Hg, P = 0.59 for mean 24-h SBP and 1.2 +/- 2.8 mm Hg, P = 0.83 for mean 24-h DBP was observed. Intraplatelet Ca2+ decreased whereas intraplatelet magnesium (Mg2+) and erythrocyte K+ increased in the intervention group. Change in mean 24-h SBP in the pooled group correlated with both change in intraplatelet Ca2+ (r = 0.49, P < 0.05) and NHE-1 activity (r = 0.6, P < 0.001). The contribution of intraplatelet Ca2+ was attenuated when both parameters were entered in a multivariate regression model. CONCLUSIONS: The present study shows a weak, statistically nonsignificant trend towards association of Ca2+ supplementation on 24-h BP in hypertensive subjects with type 2 diabetes. However, our results indicated an interrelation of [Ca2+]i levels and NHE-1 activity on BP in patients with hypertension and type 2 diabetes.

Oral magnesium supplementation reduces ambulatory blood pressure in patients with mild hypertension.

BACKGROUND: Accumulating evidence implicates a role of Mg(2+) in the pathophysiology of essential hypertension. Previous studies evaluating the antihypertensive efficacy of Mg(2+) supplementation gave contradictory results. This study aimed to investigate the effect of oral Mg(2+) supplementation on 24-h blood pressure (BP) and intracellular ion status in patients with mild hypertension. METHODS: A total of 48 patients with mild uncomplicated hypertension participated in the study. Among them, 24 subjects were assigned to 600 mg of pidolate Mg(2+) daily in addition to lifestyle recommendations for a 12-week period and another 24 age- and sex-matched controls were only given lifestyle recommendations. At baseline and study-end (12 weeks) ambulatory BP monitoring, determination of serum and intracellular ion levels, and 24-h urinary collections for determination of urinary Mg(2+) were performed in all study subjects. RESULTS: In the Mg(2+) supplementation group, small but significant reductions in mean 24-h systolic and diastolic BP levels were observed, in contrast to control group (-5.6 +/- 2.7 vs. -1.3 +/- 2.4 mm Hg, P < 0.001 and -2.8 +/- 1.8 vs. -1 +/- 1.2 mm Hg, P = 0.002, respectively). These effects of Mg(2+) supplementation were consistent in both daytime and night-time periods. Serum Mg(2+) levels and urinary Mg(2+) excretion were significantly increased in the intervention group. Intracellular Mg(2+) and K(+) levels were also increased, while intracellular Ca(2+) and Na(+) levels were decreased in the intervention group. None of the intracellular ions were significantly changed in the control group. CONCLUSION: This study suggests that oral Mg(2+) supplementation is associated with small but consistent ambulatory BP reduction in patients with mild hypertension.

Familial burden of hypertension and its effect on blood pressure levels, insulin resistance, and intracellular ions in Greek offspring.

We examined the effect of familial burden of hypertension on blood pressure (BP) levels, insulin resistance (IR), and intracellular ions in healthy offspring of Greek families with one, two, or no hypertensive parents. A total of 118 adolescents and young adults were recruited. Three groups were formed: Group A, both parents were normotensive (N-N); Group B, one parent normotensive and one hypertensive (N-H); and Group C, both parents hypertensive (H-H). BP levels, homeostasis assessment model-IR (HOMA-IR) index, and intracellular Na(+), K(+), Ca(2+), and Mg(2+) were compared in the three groups. Also, multiple regression analyses were used to create models with BP parameters and HOMA-IR as dependent variables. Offspring of H-H parents had higher body mass index (BMI) (mean difference, 4.3 +/- 0.9 kg/m(2); 95% confidence interval [CI], 2.0-6.5), higher systolic blood pressure (SBP) (mean difference, 13.2 +/- 3.1 mm Hg; 95% CI, 5.8-20.7), increased levels of intraerythrocyte Ca(2+) (mean difference, 0.02 +/- 0.01 mmol/l; 95% CI, 0.05-0.1), and fasting blood glucose (mean difference, 0.31 +/- 0.10 mmol/l; 95% CI, 0.05-0.56) when compared with those with no parental history of hypertension. In the regression model, SBP was found to be significantly affected by BMI (beta = 0.43; P < .001), iK(+) (beta = -0.224; P < .01), and gender (beta = -0.298; P < .001). The addition of the parental history showed a significant independent association of H-H parental history with SBP (beta = 0.27; P < .05). HOMA-IR was significantly determined by BMI (beta = 0.511; P < .05), iNa(+) (beta = 0.211; P < .05), and iMg(2+) (beta = -0.205; P < .05). Parental history of hypertension did not influence the HOMA-IR index. This study highlights the relative importance and contribution of environmental and genetic influences on the development of high BP. Both these influences possibly alter the intracellular ionic environment. However, nurture rather than familial hypertension burden is the key factor of IR in Greek offspring.

Blood pressure and serum potassium levels in hypertensive patients receiving or not receiving antihypertensive treatment.

OBJECTIVE: Serum potassium has a fundamental role in blood pressure (BP) regulation, and there is evidence highlighting the importance of potassium homeostasis in hypertension. The aim of this study was to determine the relationship between serum potassium levels and office BP in untreated essential hypertensives and the effect of antihypertensive medication on serum potassium levels. SETTING AND PARTICIPANTS: In a retrospective analysis, we collected data for consecutive patients first visiting our Hypertension Clinic from 1999-2004. From this population, we first selected patients who were not taking any antihypertensive medication. Patients who had conditions that could affect potassium metabolism, such as history of arrhythmias treated with digitalis, diabetes mellitus under insulin treatment, and hypo- and hyperthyroidism, were excluded from the study. From the remaining patients, those who had impaired renal function (serum creatinine > or = 1.6 mg/dL for men and > or = 1.4 mg/dl for women) and patients with secondary forms of hypertension were also excluded. The final population consisted of 817 subjects. Multivariate linear regression analysis was applied, and models were created associating serum potassium with systolic BP, diastolic BP, mean BP, or pulse pressure. The population for the second part of the study consisted of patients first visiting our Hypertension Clinic who were on one antihypertensive agent. This second group included 757 patients, 218 of whom were on beta-blockers, 42 on diuretics, 187 on angiotensin-converting enzyme (ACE) inhibitors, 287 on calcium channel blockers (CCBs), and 28 on angiotensin receptor blockers (ARBs). RESULTS: After adjusting for age, gender, and body mass index, significant negative correlations were found between serum potassium levels and systolic BP (R = -0.093, p = 0.007), diastolic BP (R = -0.078, p = 0.03), mean BP (R = -0.122, p = 0.002), and pulse pressure (R = -0.071, p = 0.044). The levels of potassium were found to be significantly lower among patients receiving diuretics than those receiving one of the other four drug categories of antihypertensive (p < 0.05 for beta-blockers, ACE inhibitors, and CCBs; p < 0.001 for ARBs). In addition, hypokalemia was found to be significantly more prevalent in the group using diuretics than the other groups. CONCLUSIONS: The observed reverse relation between serum potassium and BP supports a close pathophysiological connection between serum potassium and essential hypertension. Moreover, diuretic therapy is a significant cause of hypokalemia and requires systematic monitoring.

Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase.

BACKGROUND: Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance. OBJECTIVE: To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension. METHODS: In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters. RESULTS: Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 +/- 2.6 to 41.9 +/- 3.2 micromol/min per kg per nmol/l, P < 0.001) and the HOMA-IR index significantly decreased (6.34 +/- 0.39 versus 4.40 +/- 0.33, P < 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 +/- 1.8 versus 129.9 +/- 1.7 mmHg, P < 0.001 for systolic BP and 76.0 +/- 1.6 versus 71.9 +/- 1.6 mmHg, P < 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = -0.78, P < 0.01 and r = -0.68, P < 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 +/- 0.41 versus 7.55 +/- 0.31 mmol/l, P < 0.001), insulin (94.0 +/- 0.41 versus 79.5 +/- 5.6 pmol/l, P < 0.01) and HbA1c (8.15 +/- 0.24 versus 7.24 +/- 0.19%, P < 0.001). CONCLUSIONS: Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.