Ioannis M. Tziolas

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 μmol/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.

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.

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 (Ca2+) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca2+ ([Ca2+]i) and the transmembrane sodium–hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension.

Prevalence, awareness, treatment and control of hypertension in employees of factories of Northern Greece: the Naoussa study

The objective of this study was to examine the prevalence and the levels of awareness, control, and treatment of hypertension in workers, technicians and clerks of factories of the city of Naoussa. A total of 1976 employees in 19 units were examined. From those, 1937 (1045 men and 892 women), 15–73 years of age, were included in the analysis. Every employee was examined twice with 1 weeks interval between the two examinations. Analysis was performed using the 140/90 mmHg hypertension threshold. In every visit, three blood pressure (BP) measurements were taken with at least 1-min interval between them. In the analysis only the average BP of the second clinic visit was used. In total, hypertension prevalence was 30.5% (32.1% for men and 28.7% for women respectively, P=0.10). The levels of awareness, treatment, and control of hypertension in hypertensive patients were 18.6%, 11.8%, and 2.2%, respectively. The levels of awareness and treatment differed significantly between men and women (13.4 vs 25.4%, P<0.001 and 9.6 vs 14.8%, P<0.05), but there was no difference in the levels of control (1.5 vs 3.1%, P=0.18). Hypertension prevalence, awareness, and treatment differed also between patients <45 and ⩾45 years of age (22.0 vs 53.2%, P<0.001, 9.7 vs 28.4%, P<0.001 and 6.5 vs 17.7%, P<0.001, respectively). In conclusion, the prevalence of hypertension in our studys population is high, while the levels of awareness, treatment, and control are disappointing and should be significantly improved. There is also a difference in awareness and treatment in favour of women compared to men and in favour of patients ⩾45 years of age compared to those <45 years of age.

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 ≥1.6 mg/dL for men and ≥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 β-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 β-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.

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.

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.

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.

ORAL MAGNESIUM SUPPLEMENTATION IMPROVES INSULIN SENSITIVITY AND SERUM LIPID PROFILE IN PATIENTS WITH MILD HYPERTENSION: PP.23.436

Objective: To investigate the effect of oral magnesium supplementation on insulin sensitivity (IS) and serum lipids in patients with mild hypertension. Design and 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 magnesium 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) 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 study subjects. Results: In the group of magnesium supplementation the OGTT-derived IS indices of Stumvoll, Matsuda and Cedercholm were significantly increased between baseline and study-end, whereas Homeostasis Model Assessment-IR index and fasting insulin levels were significantly decreased. In contrast, none of these parameters were changed during follow-up in the control group. Significant reductions in total cholesterol, LDL-cholesterol and triglyceride levels along with a parallel significant increase in HDL-cholesterol levels were evident at study-end in the intervention group, but not in the control group. Conclusion: The present study suggests that oral magnesium supplementation improves IS and lipid profile in patients with mild hypertension. These potential beneficial effects of magnesium on associated metabolic factors could be helpful for patients with hypertension in terms of overall cardiovascular risk reduction.