Can the choice of diet undermine the potential genetic risk of AT1R 1166A>C gene polymorphism?

BACKGROUND: Angiotensin II type 1 receptor (AT1R) gene 1166A>C polymorphism is strongly associated with the incidence of cardiovascular diseases and predicts the development of metabolic syndrome (MetS). There is little information about the gene-diet interactions associated with MetS. This investigation examined the interaction between dietary patterns and AT1R polymorphism in relation to development risk of MetS. METHODS: A prospective, non-interventional, case-control study included 265 MetS patients and 262 healthy controls in an adult population from Croatia. Collected data included clinical variables, type of diet (Mediterranean, continental and mixed), biochemical tests and AT1R genotyping. AT1R 1166A>C genotyping was performed by PCR restriction fragment length polymorphism methods. To examine gene-diet interactions, a total predictive model was built using a hierarchical backward elimination approach. RESULTS: Participants on Continental-diet were nearly 20 times more likely to have MetS than those on Mediterranean or mixed diet (OR = 19.96; 95% CI 10.44-38.18). In multivariate prediction, control subjects with AT1R 1166AC or CC genotype had a higher risk for high triglycerides compared to the AA genotype carriers. 1166AC or CC genotype carriers more often chose Mediterranean or mixed-diet versus 1166AA genotype carriers whose choice often was continental diet. CONCLUSIONS: Our results are the first to suggest the possibility that the choice of diet can undermine the potential genetic risk of the AT1R polymorphism as polymorphism carriers may spontaneously choose the Mediterranean-diet.

High-salt diet and hypertension: focus on the renin-angiotensin system.

A high-salt diet is one of the major risk factors in the development and maintenance of hypertension. Numerous experimental and observational studies have confirmed the association of sodium intake with blood pressure levels. The effects of a high-salt diet are related to the function of the renin-angiotensin system, which is normally suppressed by a high-salt diet. Endothelial dysfunction probably plays an important role in the influence of high sodium intake on blood pressure, although the exact mechanisms remain elusive. Genetic factors are known to be very important, and various consomic and congenic rat strains as animal models have proven to be very useful in bringing us a step closer to understanding the interaction between salt intake and hypertension. In this article, experimental data obtained in studies on animals and humans, as well as epidemiological data are reviewed.

The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones.

OBJECTIVE: To assess the spasmolytic effect of drotaverine hydrochloride in colicky pain caused by renal and ureteric stones. PATIENTS AND METHODS: In a placebo-controlled, multicentre, multinational, randomized, double-blind study changes in the intensity of pain were recorded using a visual analogue scale (VAS), a four-grade (five points) pain intensity (PI) scale and a pain-relief scale. The primary endpoint was the evaluation of the antispasmodic effect of drotaverine during a 3-h study period, to confirm that drotaverine abolished or significantly decreased the intensity of pain in renal colic. The painkilling effect was defined as a decrease by at least half in the PI scale, and/or a >or= 40% decrease in the VAS 40 min after either the first or the second injection of 80 mg drotaverine or placebo (if necessary the dose could be repeated once). In all, 140 patients were enrolled but 38 withdrew, leaving 102 patients for analysis (48 drotaverine, 54 placebo; mean age 42.5 years, sd 11.25, and 41.7, sd 10.79). RESULTS: Drotaverine was effective in 79% of patients and placebo in only 46% (P < 0.001). There were no serious adverse effects. There were 20 minor side-effects in the drotaverine and four in the placebo group; none of the patients required treatment. The most frequent side-effects were a transitory decrease in blood pressure, vertigo, nausea or vomiting. CONCLUSION: Intravenous drotaverine provides effective pain relief in more than two-thirds of patients with renal colic, with no serious side-effects.

[Refractory arterial hypertension--where is the refractoriness? Hic rhodus, hic salta!]. / Refraktorna arterijska hipertenzija--u cemu je tvrdokornost? Hic rhodus, hic salta!

Arterial hypertension (AH) is the major independent risk factor for cardiovascular and cerebrovascular morbidity and mortality. Success in treatment of hypertonic patients is currently still far from acceptable in developing countries but also in the most of the developed countries in the world. There are numerous reasons and explanations for such poor therapeutic outcome, with poor patient's awareness of the need to pay attention to his own health and occasional superficial physician's approach being only some of them. However, AH treatment may present as an exceptional problem in some patients. Despite sufficient therapy duration and optimal doses of three types of antihypertensives, including one diuretic, no decrease in arterial blood pressure was observed in a low number of patients, so that such AH is called refractory (RH). RH may be primary if present since the beginning of treatment, or secondary if presenting after a period of successful treatment. In case of secondary RH, secondary forms of AH should be considered, like renovascular hypertension, primary aldosteronism, etc. In cases of primary RH, it is necessary to exclude pseudohypertension, pseudoresistance and pseudotolerance before characterizing a patient as really resistant, when the cause should be primarily sought in pathomechanisms of those organ systems which otherwise play an important role in AT homeostasis or in etiopathogenesis of AH, i.e. in kidney and heart. A significant reason for refractoriness may be drug interactions or applications of hypertensives which are not an optimal choice according to hemodynamic or hormone background of increased blood pressure. Clearly, it is not always easy to determine the background of refractoriness in practice, yet fortunately such patients are not frequent and additional efforts dedicated to them are not at the time needed for other patients. In this paper we presented a review of the most frequent causes of refractoriness in AH treatment, possible errors in diagnosing RH, and pathomechanisms responsible for the occurrence of resistance. Prognosis of RH is considerably worse than in otheR hypertonic patients and, since the possibilities of treatment are not extensive, a review of possible therapeutic approaches is also presented depending on the pathogenetic background of resistance. As RH patients have increased body mass index, and the success of the therapy was observed to depend on the salt intake, particular attention should be paid to instructions for patients on the change in lifestyle. The treatment of RH patients is a serious challenge which may unfortunately be frustrating and not infrequently have a fatal outcome due to either disease progression or patient's obstinacy.

Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension. Losartan Trial Investigators.

OBJECTIVE: The goal of this multicenter, double-blind, randomized, parallel-group study was to compare the effects of losartan potassium (hereafter referred to as losartan), candesartan cilexitil (hereafter referred to as candesartan), and losartan/hydrochlorothiazide (HCTZ) in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] 95-115 mm Hg). METHODS: A total of 1161 patients were randomized in a 2:2:1 ratio to 12 weeks of treatment with losartan 50 mg QD, possibly titrated to 100 mg QD (n = 461); candesartan 8 mg QD, possibly titrated to 16 mg QD (n = 468); or losartan 50 mg QD, possibly titrated to losartan 50 mg plus HCTZ 12.5 mg QD (n = 232). At 6 weeks, the regimens of patients not reaching a goal SiDBP <90 mm Hg were titrated as described, whereas patients achieving this goal continued with low-dose monotherapy. The single primary end point at 12 weeks tested the equivalence of the 2 monotherapy regimens, predefined as a maximum between-treatment difference in the mean change from baseline trough SiDBP of 2.5 mm Hg. RESULTS: At 12 weeks, changes in SiDBP/sitting systolic blood pressure (SiSBP) of -12.4/-14.4 mm Hg with losartan 50 mg/100 mg and -13.1/-15.8 mm Hg with candesartan 8 mg/16 mg demonstrated equivalence between the 2 monotherapy regimens (95% CI for difference in SiDBP, -1.6 to 0.2). At 12 weeks, the losartan 50 mg/50 mg plus HCTZ 12.5 mg regimen had reduced SiDBP/SiSBP significantly more (-14.3/-18.0 mm Hg) than either the candesartan 8 mg/16 mg (SiDBP, P = 0.045; SiSBP, P = 0.017) or losartan 50 mg/100 mg regimen (SiDBP and SiSBP, P = 0.001). During the last 6 weeks, patients whose regimen had been titrated to losartan 50 mg plus HCTZ 12.5 mg (n = 114) showed a greater reduction in SiDBP/SiSBP (-14.5/ -18.7 mm Hg) than did those whose regimen had been titrated to either losartan 100 mg (-10.5/-12.3 mm Hg; n = 211) or candesartan 16 mg (-11.5/-13.2 mm Hg; n = 206), representing a clinically meaningful > or = 2.5-mm Hg) difference. All 3 treatments were well tolerated, with few patients experiencing drug-related adverse events (6.9% losartan 50 mg/100 mg, 7.5% candesartan 8 mg/16 mg, 3.0% losartan 50 mg/ 50 mg plus HCTZ 12.5 mg). Candesartan 8 mg/16 mg increased serum uric acid levels (0.13 mg/dL; 95% CI, 0.04 to 0.23), whereas losartan 50 mg/100 mg decreased them (-0.14 mg/dL; 95% CI, -0.24 to -0.04), and losartan 50 mg/50 mg plus HCTZ 12.5 mg left them unchanged (0.06 mg/dL; 95% CI, -0.07 to 0.20). CONCLUSIONS: Losartan 50 mg/100 mg and candesartan 8 mg/16 mg were comparable treatments in terms of blood pressure reduction. After titration, losartan 50 mg plus HCTZ 12.5 mg was superior to either candesartan 16 mg or losartan 100 mg in reducing hypertension. Losartan, but not candesartan, lowered serum uric acid levels and attenuated the expected increase in uric acid levels with HCTZ 12.5 mg.

[Measurement of arterial pressure with a mercury sphygmomanometer more than a technique]. / Mjerenje arterijskog tlaka zivinim tlakomjerom--vise od tehnike.

Arterial blood pressure has been measured using mercury sphygmomanometer and auscultatory method for more than a hundred years. The results obtained by this measurement method make the basis of almost all conclusions related to pathogenesis, epidemiology and treatment of arterial hypertension. However, some deviations from ordinarily obtained data have been observed but are undoubtedly due to superficial approach to this simple method. A number of lesser faults can together result in an eventually inaccurate conclusion both regarding diagnosis and assessment of therapeutic effects. The aim of this short review article is to remind us of those little efforts needed to be done for improving the exactness of measurement in order to increase the accuracy of results. The ultimate consequence should be better care of patients with high blood pressure.

[Epidemiology of arterial hypertension in Croatia in 2000]. / Epidemiologija arterijske hipertenzije u Hrvatskoj 2000. (EH-UH 2000).

Arterial hypertension is one of the most important modifiable risk factors for cardiovascular disease. Treatment of hypertension has been shown to decrease the risk of myocardial infarction, stroke, congestive heart failure, end-stage renal disease and peripheral vascular disease. It is apparent from some results that blood pressure should be lowered in all patients having other cardiovascular risk factors regardless whether they are hypertensive or non-hypertensive persons. However, complete information considering awareness, treatment and control of arterial hypertension is still missing. The aim of our study is to obtain these data for the entire region of the Republic of Croatia. The study will be finished in two years and new hypertension related cardiovascular risk indicators such as isolated systolic hypertension, pulse pressure and heart rate will be analysed as well. Therapeutic success will be analysed in particular subpopulations considering applied therapy.

Complete remission of cryoglobulinemic glomerulonephritis (HCV-positive) after high dose interferon therapy.

We report the case of a 64-year old woman with hepatitis C virus infection, mixed cryoglobulinemia type II (IgG + IgM kappa) and cryoglobulinemic glomerulonephritis. The patient was treated with the standard dose of recombinant interferon alpha-2b (3 million units 3 times a week) for one year, resulting in complete clinical remission and undetectable levels of serum hepatitis C virus RNA. AST and ALT normalized and proteinuria decreased from 2.78 to 0.98 g/day. However, a relapse occurred when therapy was stopped. Additional therapy with interferon-alpha (5 million units 3 times a week for 9 months) resulted again in quick and prolonged remission. The clinical course of our patient showed sustained clinical and virologic response after high-dose interferon-alpha treatment confirming the usefulness of interferon alpha in treatment of patients with cryoglobulinemic glomerulonephritis. Our observation is in agreement with others, suggesting that recommended standard dosage and duration of initial treatment with interferon alpha should be re-evaluated. Although our patient had sustained virologic and clinical response after interferon alpha monotherapy, recent studies clearly support combination therapy of interferon alpha and ribavirin for treatment of chronic HCV infections.

Antibodies to Tamm-Horsfall protein in endemic nephropathy.

BACKGROUND: The aim of the study was to investigate the possible role of antibodies to Tamm-Horsfall protein (anti-THP) in the early diagnosis of endemic nephropathy (EN). METHODS: Anti-THP (IgA, IgM, IgG classes) antibodies were determined by direct ELISA in a random sample of 159 subjects from the endemic village of Kaniza who were divided into four groups according to the WHO criteria, i.e., 'diseased', 'suspect', 'at risk', and 'others'. These groups were compared to subjects from the non-endemic village of Klakar and healthy subjects from Zagreb. RESULTS: No differences for all the classes of antibody were observed among the groups of subjects from the endemic village of Kaniza (P>0.05) or between these subjects and those from the non-endemic village of Klakar (P>0.05). The values of IgM anti-THP antibodies exceeded those of the IgA and IgG classes in all groups of subjects (P<0.05). The values for all three classes of antibodies were higher in the rural than the urban population (P<0. 05). CONCLUSION: Determination of anti-THP antibodies was not found to be useful in the early diagnosis of endemic nephropathy. The results suggest that most of the anti-THP antibodies are 'natural' and/or cross reactive. The highest values observed in the rural population could probably be explained by exposure to some ubiquitous antigen or more likely they are consequences of fever.

Antibodies to Tamm-Horsfall protein in patients treated with extracorporeal shock wave lithotripsy (ESWL).

The aim of this study was to determine antibodies to Tamm-Horsfall protein in patients with nephrolithiasis treated with extracorporeal shock wave lithotripsy (ESWL). The values of antibodies to Tamm-Horsfall protein were determined by direct enzyme immunoassay. No statistically significant differences (P > 0.05) were observed for the IgG and IgM classes of antibodies between the groups of healthy subjects and patients with nephrolithiasis before, and 30 and 60 days after ESWL. The values of IgA class determined 30 days after treatment were significantly higher (P < 0.05) in patients, which could be due to the stimulation of the immune system. The highest values of antibodies to Tamm-Horsfall protein were obtained in both groups in the test with secondary antibodies directed toward IgM class, implicated at the presence of cross-reactive antibodies. Determination of antibodies to THP subunits isolated form urine of patients with nephrolithiasis should be performed.

Antibodies to Tamm-Horsfall protein subunits prepared in vitro, in patients with acute pyelonephritis.

The aim of this study was to determine antibodies to Tamm-Horsfall protein subunits in patients with acute pyelonephritis. The protein subunits used in this determination were prepared by chemical treatment of Tamm-Horsfall protein isolated from the urine of healthy individuals. Values for IgG and IgA were significantly higher (p < 0.05 and p < 0.01 respectively) in patients than in healthy persons, while IgM class antibodies were significantly higher only in the test performed with subunits obtained with 8.3 mol/l acetic acid (THP-A) (p < 0.05). Values for all three classes determined in the test with THP-A were significantly higher in patients with vesicoureteral reflux than in patients with normal radiological findings (p < 0.05). Antibodies to Tamm-Horsfall protein subunits isolated from the urine of patients with acute pyelonephritis should also be determined.

[Hyperinsulinemia and arterial hypertension]. / Hiperinzulinemija i arterijska hipertenzija.

Data concerning hyperinsulinemia/insulin resistance in the pathogenesis of essential hypertension are presented. Approximately 50% of hypertensive patients have insulin resistance. The prime site of insulin resistance is in the skeletal muscle affecting non oxidative glucose metabolism (glycogen synthesis). Effects of insulin on the kidney points toward possible, but not the key role of the hyperinsulinemia in the pathogenesis of arterial hypertension. According to some results hypertension causes hyperinsulinemia/insulin resistance through hemodynamic alterations and structural changes of blood vessels. On the other hand, there is no hyperinsulinemia in the secondary forms of arterial hypertension. This is an argument against hypertension as a prime cause in insulin resistance inception. The importance of metabolic alterations of lipid status and fibrinolytic system in patients with hyperinsulinemia has been emphasized. These metabolic changes increase cardiovascular risk. Effects of antihypertensive drugs on glucose metabolism and insulin sensitivity are reported. In conclusion, hyperinsulinemia per se is not a risk factor. However, when connected with other metabolic disturbances (dyslipidemia, hypertension, hyperuricemia, disorders of fibrinolysis) it increases the risk of cardiovascular diseases.

Antibodies to Tamm-Horsfall protein in patients with acute pyelonephritis.

The role of antibodies to Tamm-Horsfall protein in the diagnosis of acute pyelonephritis was studied. Antibodies to Tamm-Horsfall protein were also determined in a group of normal subjects. Patients with acute pyelonephritis were divided into subgroups according to the concurrent presence of vesicoureteral reflux or nephrolithiasis. No statistically significant differences (p > 0.05) were observed for any class of antibodies (IgG, IgA and IgM) between the groups of healthy subjects and patients with acute pyelonephritis, regardless of the presence or absence of vesicoureteral reflux or nephrolithiasis. Values for different antibody classes showed that IgM antibodies were the most abundant in all the groups examined. A difference in the values of IgM relative to IgA and IgG antibodies was found to be statistically significant in the patient group only (p < 0.05). In patients with vesicoureteral reflux, there was no statistically significant difference (p > 0.05) between the values of IgM and of other antibody classes. In these patients, however, the highest values of all the three antibody classes were obtained, although these differences were also not statistically significant (p > 0.05). The results pointed to the need of further studies of the role of antibodies to Tamm-Horsfall protein in the diagnosis and pathogenesis of tubulointerstitial nephritis.

[Hyperuricemia and plasma renin activity in essential arterial hypertension]. / Hiperuricemija i reninska aktivnost plazme u esencijalnoj arterijskoj hipertenziji.

The frequency of hyperuricemia in 253 patients with essential hypertension (EH) was studied. The level of uric acid in serum and frequency of hyperuricemia were determined in patients divided according to sex and renin plasma activity (RPA). High values of uric acid in serum were found in a total of 69 patients (27.3%), of which there were 40 males (30.1%) and 29 females (24.2%). The highest values of uric acid were found in those with high RPA, but the difference was significant only in males (p < 0.05). No correlation was observed between the values of the uric acid in serum and RPA in none of the renin subgroups. On the basis of our study, it was not possible to explain the high values of uric acid in serum in patients with EH, especially in those with high plasma renin activity, as well as the role of renin-angiotensin-aldosterone system in the pathogenesis of hyperuricemia.

[Renin levels in renal veins in patients with essential arterial hypertension]. / Vrijednosti renina iz bubreznih vena u bolesnika s esencijalnom arterijskom hipertenzijom.

The data on plasma renin activity (PRA) obtained by catheterization of renal veins in 272 patients with essential arterial hypertension (EH) are reported. In order to exclude a secondary nature of hypertension, all patients were hospitalized and submitted to the extensive clinical and laboratory examinations (according to the protocol) including renal angiography. The aim of the work was to get evidence whether in the apparently homogeneous group of patients with EH there are differences in renin activity between the renal veins giving the quotient (Q) higher than 1.5, and possibly to recognize the clinical meaning of the differences of Q found. In the examined patients as a whole regardless of PRA, 50 of them (18.3%) showed Q greater than or equal to 1.5 and among them in 16 (5.8%) patients Q greater than or equal to 2 was found. The patients were divided according to PRA into those with low, normal and high PRA. In the hyperreninemic group of patients no Q greater than or equal to 2.0 has been found. In the hyporeninemic group 9 patients (9.9%) exhibited Q greater than or equal to 2.0. Although, one does not expect in EH to find differences in PRA between left and right renal vein, we have found the values of Q greater than or equal to 1.5 in nearly 1/5 of our patients. These differences found could be resulting from the existence of asymmetrical angiosclerotic or other renal pathological changes that can not be examined by the available clinical methods.(ABSTRACT TRUNCATED AT 250 WORDS)