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Maciej Tomaszewski

Publications and source records attributed to Maciej Tomaszewski.

16 recordsLinked to original sources
PubMed2026

Urate-lowering effects of losartan: a meta-analysis of randomised controlled trials and target trial emulation.

Common in hypertensive patients, hyperuricaemia is often exacerbated by guideline-recommended antihypertensive therapies such as thiazide diuretics. Losartan is known as an angiotensin II receptor type 1 antagonist with a uricosuric effect, but the magnitude of its efficacy in lowering urate has not been quantified versus a placebo-reference. We sought to quantify the urate-lowering effect of losartan versus placebo using two complementary approaches. We first conducted a meta-analysis of randomised controlled trials (RCTs) to quantify the effect of losartan on serum urate levels versus placebo. We then applied a target trial emulation framework in the UK Biobank as a secondary source of data and a replication experiment. The meta-analysis of six prospective randomised controlled trials (RCTs), including 1119 losartan-treated patients and 1093 controls, demonstrated that losartan reduced serum urate levels by approximately 0.29 mg/dL relative to placebo (95% CI: -0.46 to -0.12, p = 0.0009). In the target trial emulation, 23 losartan-treated individuals showed a reduction in serum urate of approximately 0.35 mg/dL (95% CI: -0.66 to -0.03, p = 0.03) when compared with 92 matched controls, and after accounting for 12 potential confounders including established urate-lowering therapies. Our results provide evidence for a modest yet consistent urate-lowering potential of losartan. This modest biochemical effect (~0.3 mg/dL) may be an attractive option to mitigate the diuretic-induced urate elevation. Thus, losartan can be considered as a favourable antihypertensive choice for patients managed with diuretics or those who are at risk of hyperuricaemia/gout.

Losartan↗
PubMed2006

Genetic information in the diagnosis and treatment of hypertension.

Advancement in cardiovascular science should be measured by a number of new diagnostic and therapeutic options applied in clinical practice as a result of translational research. Hypertension genetics is a good example of such a successful transfer of knowledge from bench to bedside. There are genetic methods currently used as diagnostic tools in patients presenting with secondary forms of hypertension, including primary hyperaldosteronism, Cushing's syndrome, pheochromocytoma, and chronic kidney disease. Directed treatment that corrects pathophysiologic abnormalities is available for several monogenic forms of hypertension as a result of uncovering their underlying genetic mechanisms. Progress in hypertension pharmacogenetics and pharmacogenomics brings closer a perspective of personalized antihypertensive treatment and gene transfer strategies, which, although still considered as innovative approaches, may soon become options to treat, control, and, possibly, cure hypertension.

Adrenocortical Hyperfunction↗
PubMed2005

Corcoran Lecture. Cardiovascular genomics and oxidative stress.

The majority of modifiable cardiovascular risk factors are complex, polygenic, or at least oligogenic traits, with genetic and environmental determinants playing important roles in disease risk and its phenotypic expression. The Human Genome Project and subsequent mouse and rat genome data have provided powerful tools to commence the dissection of genetic determinants of hypertension and other cardiovascular risk factors. Despite several new methodologies such as genome-wide scans, genome-wide gene expression profiling, and proteomic screens, it is fair to say that the progress of genetic studies designed as nonhypothesis driven has been relatively slow. On the other hand, several interesting candidate pathways have been identified, where investigators allowed for hypothesis-driven functional studies. One example of such pathway is vascular oxidative stress with its extensive network of genes and proteins, many with proven contributions to cardiovascular disease. Therefore, in parallel to genome-wide or proteome-wide studies, it will be constructive to pursue "pathwayomics" defined here as functional studies of a candidate pathway for disease pathogenesis.

Animals↗
PubMed2005

Selected climatic variables and blood pressure in Central European patients with chronic renal failure on haemodialysis treatment.

UNLABELLED: BACKGROUND/AIMS;Higher blood pressure (BP) in winter has been documented in healthy and hypertensive adults. It may potentially contribute to the observed excess winter cardiovascular mortality in the general population. The aim of the study was to assess whether BP varies similarly among patients with chronic renal failure on haemodialysis treatment, who present an increased risk of cardiovascular death. METHODS: We retrospectively analysed values of pre-dialysis BP and parameters of fluid retention--pre-dialysis body weight and inter-dialytic weight gain measured in 49 patients (23 male, 26 female; aged 46.0+/-13.5 years) from 1995 to 1998. For each patient we calculated deviations of monthly mean values of systolic BP, diastolic BP, pre-dialysis body weight and inter-dialytic weight gain from the lowest monthly means of these parameters in a given year. Monthly means of these deviations for the whole study group (dSBP, dDBP, dBW, dWG, respectively) were subsequently computed. Monthly means of air temperature (T), air relative humidity (H) and atmospheric pressure (AP) were provided by the local Institute of Meteorology. The Wilcoxon paired test was applied to compare mean values of BPs and parameters of fluid retention of every patient in three warmest and three coldest months of each year. Spearman rank correlation analysis was employed to evaluate relationships between dSBP, dDBP and climatic variables, dBW or dWG. RESULTS: Systolic BP was higher in summer than in winter (146.6+/-20.5 vs 143.4+/-18.9 mmHg; p<0.00001). Diastolic BP was also higher in summer than in winter (82.6+/-8.5 vs 79.6+/-7.3 mmHg; p<10(-9)). Pre-dialysis body weight and inter-dialytic weight gain did not differ between summer and winter (66.0+/-13.2 vs 66.0+/-13.2 kg; p=0.98 and 2.27+/-0.6 vs 2.29+/-0.5 kg; p=0.53). There was a positive correlation between dSBP and T (RS=0.424, p<0.003), as well as dDBP and T (RS=0.591, p<0.00001) and an inverse correlation between dSBP and H (RS=-0.372, p<0.01), as well as dDBP and H (RS=-0.408, p<0.004). There were no significant associations between BPs and AP, dBW or dWG. CONCLUSIONS: In haemodialysed patients from southern Poland, BP is higher in summer than in winter. Changes in BP are related to seasonal changes in climatic variables--air temperature and air relative humidity. Seasonal variation in BP is not associated with variation in fluid retention. Possible alteration of cardiovascular reactivity to changes in climatic environment in haemodialysed chronic renal failure patients may be one of the potential explanations of these observations.

Adult↗
PubMed2004

Epistatic interaction between beta2-adrenergic receptor and neuropeptide Y genes influences LDL-cholesterol in hypertension.

Beta2-adrenergic receptor gene and neuropeptide Y gene may potentially influence lipid metabolism and overall energy balance. Therefore, we examined associations of these genes with lipid fractions and obesity-related phenotypes in hypertensive subjects. A total of 638 white individuals from 212 Polish families with clustering of essential hypertension were phenotyped for cardiovascular risk determinants. Each subject was genotyped for functional polymorphisms of beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu) and neuropeptide Y (Leu7Pro). Of 3 common haplotypes of beta2-adrenergic receptor gene, Arg16Gln27 was overtransmitted to offspring with elevated levels of total cholesterol (Z=2.2; P=0.026) and LDL-cholesterol (Z=3.2; P=0.002). Individually, Leu7Pro was not associated with any of the metabolic phenotypes in family-based tests or case-control analyses. However, in the presence of Arg allele of Arg16Gly and Gln allele of Gln27Glu, homozygosity for Leu variant of the Leu7Pro polymorphism was associated with 2.1-increased odds ratio (confidence interval, 1.10 to 3.81; P=0.024) of elevated LDL in hypertensive subjects, independent of age, gender, body mass index, adjusted blood pressures, antihypertensive therapy, and use of nonselective beta-blockers and diuretics. Consistently, there was a significant multilocus association among variants of Arg16Gly, Gln27Glu, and Leu7Pro in hypertensive probands with elevated LDL (cases; P=0.028) but not in hypertensive subjects with normal LDL (controls). This study revealed an association of LDL-cholesterol with beta2-adrenergic receptor gene haplotype and provided evidence for epistatic interaction between beta2-adrenergic receptor gene and neuropeptide Y gene in determination of LDL-cholesterol in patients with essential hypertension.

Cholesterol, LDL↗
PubMed2004

Serum C-reactive protein and lipids in ultra-Marathon runners.

In this investigation, we compared lipid and inflammatory parameters in regular long distance runners with matched sedentary controls. Long distance runners had significantly lower low-density lipoprotein cholesterol and C-reactive protein levels than the control group. This exercise-induced reduction in low-density lipoprotein cholesterol was independent of the decrease in C-reactive protein levels.

Adult↗
PubMed2003

Association of the human Y chromosome with cholesterol levels in the general population.

OBJECTIVE: Males are at higher risk of cardiovascular diseases than females. The aim of the study was to test whether the potential of the Y chromosome to affect cardiovascular risk could be attributed to its influence on lipids. METHODS AND RESULTS: 1288 Polish men (1157 subjects from young healthy cohort and 131 individuals from middle-aged hypertensive population) were phenotyped for determinants of cardiovascular risk including BMI, blood pressures, lipids, and testosterone. Each subject was genotyped for the HindIII(+/-) polymorphism within the nonrecombining region of the Y chromosome. Men with the HindIII(-) variant exhibited significantly higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels than subjects with the HindIII(+) genotype in both populations. The differences between the genotypes were 0.15 mmol/L (P=0.0107) and 0.45 mmol/L (P=0.0377) in TC and 0.15 mmol/L (P=0.0059) and 0.41 mmol/L (P=0.0432) in LDL among young apparently healthy men and middle-aged hypertensive men, respectively. The HindIII(+) was associated with a significant increase in blood pressure of the middle-aged men. Testosterone serum concentrations correlated positively with HDL-cholesterol levels, and this association was independent of the Y chromosome. CONCLUSIONS: The results indicate that a locus/loci on the Y chromosome may influence LDL levels, independent of testosterone levels.

Adult↗
PubMed2003

Strikingly low circulating CRP concentrations in ultramarathon runners independent of markers of adiposity: how low can you go?

OBJECTIVE: This study was undertaken to evaluate to what extent C-reactive protein (CRP) can be reduced by exercise by examining its circulating concentrations in male ultramarathon runners and to determine if low leptin as a robust circulating marker of fat mass could account for low CRP in such men. METHODS AND RESULTS: Sixty-seven male ultramarathon runners and 63 sedentary male controls of similar age and body mass index were recruited. CRP and leptin were measured by ELISA and radioimmunoassay, respectively. Median CRP concentration in lean (body mass index <25 kg/m2) marathon runners was less than half control median (0.4 [0.2 to 0.9] mg/L versus 0.9 [0.5 to 2.7] mg/L, P=0.0013) and, more strikingly, in nonlean runners was approximately 26% of control median (0.4 [0.3 to 0.8] mg/L versus 1.5 [0.9 to 2.5] mg/L, P=0.0002). Circulating leptin levels were also substantially lower in lean (45% less) and nonlean (63% less, both P<0.0001) ultramarathon runners. However, interleukin-6 levels were not different. Furthermore, leptin adjustment only minimally attenuated the case-control difference in CRP, suggesting that mechanisms other than fat mass reduction contribute to low concentrations of CRP in marathon runners. CONCLUSIONS: This study suggests that circulating CRP concentrations can be markedly suppressed, independently of total adiposity or indeed fat mass, by intense regular physical exercise.

Adult↗
PubMed2003

[Erythropoietin administration in diabetic patients].

This paper presents the role of erythropoietin application in diabetic patients with accompanying renal failure. The main cause of anemia in diabetics are: nephropathy, structural lesions of erythrocyte membrane and blood loss connected with diagnostic and therapeutic actions. There are publications which demonstrate that in patients with diabetes type 1 or 2 with accompanying nephropathy, anemia appears more frequently than in the group of patients with chronic renal failure caused by other factors. It is supposed, that the impaired erythropoietin synthesis in diabetics can be caused by autonomic neuropathy. Erythropoietin administration in case of diabetic nephropathy has a beneficial influence on fat metabolism, immune response and reduction of insuline resistance. Erythropoietin because of reduction of vascular endothelial growth factor synthesis blocks the development of diabetic retinopathy and macroangiopathy. Erythropoietin reduces the risk of the left-ventricular hypertrophy caused by anemia. Very important is that the erythropoietin resistance is lower in diabetics. Scientists who are adverse to erythropoietin administration in patients with diabetic nephropathy maintain, that it can lead to vascular complications and the deterioration of glycemia control.

Anemia↗
PubMed2003

[Monogenic hypertension].

The results of many studies performed on animals and humans strongly suggest that genetic factors lead to the development of hypertension (HT). Syndromes in which mutations in single genes are sufficient to result in large changes of blood pressure are rare. Nevertheless, it is anticipated that their understanding will lead to new insights into forms of hypertension occurring more often, including essential hypertension. At least 9 monogenic forms of HT including Liddle syndrome, type I familial hyperaldosteronism (GRA) and type II familial hyperladosteronism, Gordon syndrome, apparent mineralocorticoid excess syndrome (AME), hypertension associated with type E brachydactyly, glucocorticoid receptor mutations, type IV congenital adrenal hyperplasia (CAH) (11 beta-hydroxylase deficiency), and type V CAH (17 alpha-hydroxylase deficiency) have been described so far.

Animals↗
PubMed2003

[Role of advanced glycosylation end products in the pathogenesis of hypertension].

Advanced glycosylation end products (AGEs) are involved in the patho-genesis of diabetes mellitus, end stage renal failure, hypertension and its complications. The influence of AGEs on hypertension is exerted by oxidative stress, vascular remodelling, impaired nitric oxide metabolism, and immunological disturbances. The investigations aiming to explain the reasons of disturbed metabolism of AGEs in hypertension will implicate therapeutic interventions.

Diabetes Complications↗
PubMed2002

Essential hypertension and beta2-adrenergic receptor gene: linkage and association analysis.

A region on human chromosome 5 (5q31.1-qter) contains several genes that encode important blood pressure regulators and thus is a good candidate for analysis of linkage and association with hypertension. We recruited 638 individuals from 212 Polish pedigrees with clustering of essential hypertension. These subjects were genotyped for 11 microsatellite markers that span this region to test for linkage to essential hypertension and systolic and diastolic blood pressures. The segment of this region of approximately 7 cM delineated by D5S1480 and D5S500 markers was linked to blood pressures in multipoint analysis. In 2-point analysis, D5S1480--the marker in close proximity to beta2-adrenergic receptor gene--reached the maximal linkage to essential hypertension and adjusted systolic and diastolic blood pressures, implicating this gene as a positional candidate for further association studies. Arg16Gly, Gln27Glu, and Thr164Ile--3 functional single nucleotide polymorphisms within the beta2-adrenergic receptor gene--were tested for association with essential hypertension. None of these polymorphisms showed a significant association with essential hypertension, separately or in the haplotype analysis. This study provided evidence of linkage of 5q31.1-5qter region to essential hypertension in the European population. Moreover, it implicated the chromosomal segment in close proximity to D5S1480 and D5S500. The detailed analysis of 3 single nucleotide polymorphisms does not support the role of the beta2-adrenergic receptor gene as a major causative gene for the detected linkage.

Adult↗
PubMed2002

The Y chromosome effect on blood pressure in two European populations.

Higher blood pressure (BP) in males compared with females is well documented and is thought to be influenced in part by the Y chromosome. To examine whether there is an association between BP and a polymorphic HindIII biallelic marker in the nonrecombining region of the Y chromosome, we genotyped 155 males from a Polish study group and 762 males from a Scottish study group. We also tested for possible interaction between the Y chromosome and a mutation in the steroidogenic factor binding site of the aldosterone synthase gene by genotyping the same group from Scotland. There was no significant difference in age or body mass index between 2 Y chromosome genotypes in both study groups. Men with the HindIII(+) genotype had significantly higher systolic and diastolic pressures than those with the HindIII(-) genotype in both the Polish and Scottish studies. This difference between the genotypes was 5.27 mm Hg (P=0.0014) and 3.14 mm Hg (P=0.0005) for adjusted systolic BP and 2.6 mm Hg (P=0.0045) and 1.44 mm Hg (P=0.0084) for adjusted diastolic BP in the Polish and the Scottish studied, respectively. On binary logistic regression analysis, males with the HindIII(+)/TT SF1 genotype combination had an odds ratio for elevated BP of 3.92 (CI 1.21 to 12.68, P=0.023). Our results indicate that the Y chromosome harbors a locus or loci that contribute to BP variation in hypertensive and normotensive men. The polymorphism in the aldosterone synthase gene may interact with the Y chromosome to increase the odds of an individual's developing higher BP.

Adult↗
PubMedDate not supplied

Y is there a risk to being male?

Being male or female can make a vital difference to many important biological functions and can lead to disparities in health. The Y chromosome carries the sex-determining sex reversal Y (SRY) gene and recent studies show that it might also harbor genes that have important biological functions other than sex determination. One such example is the emerging evidence from animal models and humans that supports the presence of cardiovascular genes on the Y chromosome. A significant amount of work remains to identify these genes; however, we report here observations linking the Y chromosome to hypertension, which could explain the higher incidence of cardiovascular disease in males compared with females.

Animals↗