Ludovit Gaspar

Probiotics in prevention and treatment of obesity: a critical view.

The worldwide prevalence of obesity more than doubled between 1980 and 2014. The obesity pandemic is tightly linked to an increase in energy availability, sedentariness and greater control of ambient temperature that have paralleled the socioeconomic development of the past decades. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. The gut microbiota as an environmental factor which influence whole-body metabolism by affecting energy balance but also inflammation and gut barrier function, integrate peripheral and central food intake regulatory signals and thereby increase body weight. Probiotics have physiologic functions that contribute to the health of gut microbiota, can affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community.

Small high-density lipoprotein is associated with monocyte subsets in stable coronary artery disease

Objective: High-density lipoprotein (HDL) particles are heterogeneous in structure and function and the role of HDL subfractions in atherogenesis is not well understood. It has been suggested that small HDL may be dysfunctional in patients with coronary artery disease (CAD). Monocytes are considered to play a key role in atherosclerotic diseases. Circulating monocytes can be divided into three subtypes according to their surface expression of CD14 and CD16. Our aim was to examine whether monocyte subsets are associated with HDL subfractions in patients with atherosclerosis. Methods: We included 90 patients with angiographically stable CAD. Monocyte subsets were defined as classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). HDL subfractions were measured by electrophoresis on polyacrylamide gel. Results: Serum levels of small HDL correlated with circulating pro-inflammatory NCM and showed an inverse relationship to circulating CM independently from other lipid parameters, risk factors, inflammatory parameters or statin treatment regime, respectively. IM were not associated with small HDL. In particular, patients with small HDL levels in the highest tertile showed dramatically increased levels of NCM (14.7 ± 7% vs. 10.7 ± 5% and 10.8 ± 5%; p = 0.006) and a decreased proportion of CM (79.3 ± 7% vs. 83.7 ± 6% and 83.9 ± 6%; p = 0.004) compared to patients in the two lower tertiles. In contrast, intermediate HDL, large HDL and total HDL were not associated with monocyte subset distribution. Conclusion: Small HDL levels are associated with pro-inflammatory NCM and inversely correlated with CM. This may suggest that small HDL could have dysfunctional anti-inflammatory properties in patients with established CAD.

The effects of atorvastatin treatment on the mean platelet volume and red cell distribution width in patients with dyslipoproteinemia and comparison with plasma atherogenicity indicators—A pilot study

OBJECTIVES The mean platelet volume (MPV) and red cell distribution width (RDW) have recently arisen interest because of their association with an increased cardiovascular risk. The aim of our study was, therefore, to determine whether an association exists between MPV, RDW and lipoprotein sub-fractions, and to show the impact of statin therapy on these new possible biomarkers of atherosclerotic risk. DESIGN AND METHODS A cohort of 40 patients with hypercholesterolaemia (29 females, mean age 62.9±9 years), without previous hypolipidaemic treatment were enrolled. The patients were treated with atorvastatin 40 mg/day for 12 weeks. Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density cholesterol (HDL-C), triglycerides (TG), LDL-C sub-fractions [large LDL-C 1-2 and small dense (sd)-LDL-C 3-7], apolipoproteins (apoA1, apoB), apoB/apoA1 ratio, atherogenic index of plasma (AIP), haematological parameters (including MPV, RDW) and safety parameters (renal, hepatic) were measured before and after 12 weeks of atorvastatin treatment. RESULTS At baseline, a strong correlation between HDL-C, TG, sd-LDL-C, apoB, apoB/apoA1, and AIP with MPV (r=-0.55, p<0.001; r=0.57, p<0.001; r=0.73, p<0.001; r=0.41, p<0.05; r=0.52, p<0.001; r=0.61, p<0.001, respectively) and RDW (r=-0.49, p<0.001; r=0.62, p<0.001; r=0.67, p<0.001; r=0.41, p<0.05; r=0.43, p<0.05; r=0.65, p<0.001, respectively) was found. After 12 weeks of treatment with atorvastatin, MPV and RDW values underwent significant modification only in those patients displaying the strongest lipid-lowering effect. CONCLUSIONS Values of MPV and RDW seem to reflect a pro-atherogenic lipoprotein profile mainly represented by the presence of sd-LDL-C.

Effect of Atorvastatin on Low-Density Lipoprotein Subpopulations and Comparison Between Indicators of Plasma Atherogenicity: A Pilot Study

Treatment with statins to achieve target low-density lipoprotein cholesterol (LDL-C) levels is still associated with residual risk. Lipoprotein subfraction evaluation can provide additional information regarding atherogenicity in these individuals. Patients (n = 40) with hypercholesterolemia (29 females, mean age 63 years), without previous hypolipemic treatment, were treated with atorvastatin 40 mg/d for 3 months. Atorvastatin significantly reduced total cholesterol (6.7 ± 1.0 vs 4.6 ± 1.3 mmol/L, P < .001), LDL-C (4.3 ± 1.0 vs 2.6 ± 0.9 mmol/L, P < .001), triglycerides (1.8 ± 0.9 vs 1.5 ± 1.00 mmol/L, P < .05), small-dense LDL (sdLDL) fraction 3 to 7 (0.22 ± 0.37 vs 0.09 ± 0.16 mmol/L, P < .001), and apolipoprotein B (apoB; 1.0 ± 0.2 vs 0.74 ± 0.2 g/L, P < .001). There was a negative correlation of atherogenic index of plasma (AIP) with buoyant LDL-1 and LDL-2 (r = −.35; P < .05) and positive with sdLDL-3 to sdLDL-7 (r = .52, P < .001). Administration of atorvastatin 40 mg/d in patients with hypercholesterolemia caused a shift in sdLDL subfractions to large, buoyant subfractions. The AIP better correlated with sdLDL than apoB levels.

Association of small dense LDL serum levels and circulating monocyte subsets in stable coronary artery disease.

Objective Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels. Methods We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel. Results Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels. Conclusion The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.

Polymorphisms of the Peroxisome Proliferator-Activated Receptor-γ (rs1801282) and its coactivator-1 (rs8192673) are associated with obesity indexes in subjects with type 2 diabetes mellitus

AbstractᅟThe aim of this study was to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PGC-1α) gene (rs8192673) are associated with obesity indexes (BMI, waist circumference) in subjects with type 2 diabetes mellitus (T2DM) in Caucasian population. The second aim was to find an association of both polymorphisms with T2DM.MethodsTwo exonic SNPs of both genes rs1801282 of the PPAR-γ gene and rs8192673 of the PGC-1α gene) were genotyped in 881 unrelated Slovene subjects (Caucasians) with T2DM and in 348 subjects without T2DM (control subjects).ResultsFemale homozygotes with the CC genotype of the rs8192673 had higher waist circumference in comparison with subjects with other genotypes. Homozygotes (females, males) with wild allele (Pro) of the rs1801282 (Pro12Ala polymorphism) had higher waist circumference in comparison with subjects with other genotypes. In the study, there were no differences in the distributions of the rs8192673 and the rs1801282 genotypes between patients with T2DM and controls. Linear regression analyses for both polymorphisms were performed and demonstrated an independent effect of the rs1801282 of the PPAR-γ on waist circumference in subjects with T2DM, whereas an independent effect on waist circumference was not demonstrated for the rs8192673 of the PGC-1α gene.ConclusionsIn a large sample of the Caucasians the rs8192673 of the PGC-1α gene and the rs1801282 of the PPAR-γ gene were associated with waist circumference in subjects with T2DM.

Orthostatic hypotension in diabetic patients—10-year follow-up study

INTRODUCTION Cardiovascular autonomic neuropathy in diabetics is a common but often underestimated and underdiagnosed complication of diabetes mellitus. One of the most clinical apparent forms of cardiovascular autonomic neuropathy is orthostatic hypotension. OBJECTIVES To retrospectively assess the association of the orthostatic hypotension (OH) with macrovascular and microvascular complications of diabetes mellitus and to determine its effect on mortality. DESIGN AND METHODS We retrospectively analyzed 187 patients with diabetes mellitus (60 patients with diabetes type 1 and 127 patients with diabetes type 2). Patients were divided into groups according to presence or absence of OH and type of diabetes. Association of OH with macrovascular and microvascular complications was evaluated and the effect of OH on 10-year all-cause mortality was also assessed. RESULTS OH was present in 31.7% of patients with diabetes type 1 (DM1) and in 32.3% of patients with diabetes type 2 (DM2). OH was positively associated with the prevalence of myocardial infarction in DM1 (OR=10.67) and with prevalence of stroke in DM2 (OR=3.33). There was also a strong association of OH and the prevalence of peripheral artery disease in both DM1 (OR=14.18) and DM2 (OR=3.26). Patients with both types of diabetes and OH had significantly higher prevalence of nephropathy (DM1 OR=8.68, DM2 OR=3.24), retinopathy (DM1 OR=8.09, DM2 OR=4.08) and peripheral neuropathy (DM1 OR=17.14, DM2 OR=7.51) Overall 10year mortality rate was higher in diabetic patients with OH. CONCLUSIONS Presence of OH in diabetics is associated with higher prevalence of macrovascular and microvascular complications of diabetes mellitus and also with higher 10-year mortality.

Atherogenic versus non-atherogenic lipoprotein profiles in healthy individuals. is there a need to change our approach to diagnosing dyslipidemia?

The electrophoretic separation of lipoproteins on polyacrylamide gels enables the quantification of nonatherogenic and atherogenic plasma lipoproteins including small dense low density lipoprotein (sdLDL) particles, which represent the atherogenic lipoprotein subpopulations in plasma. This methodology could help distinguish between nonatherogenic hyperlipidemia, normolipidemia with an atherogenic lipoprotein profile, non-atherogenic normolipidemia, and atherogenic hyperlipidemia. According to our pilot research of a normolipidemic population, the atherogenic lipoprotein profile might be present in about 6% of normolipidemic young healthy individuals. Therefore, if confirmed by other studies, it will be necessary to consider a different diagnostic approach and risk stratification for patients with atherogenic normolipidemia (as well as non-atherogenic hypercholesterolemia).

Prognostic significance of dipping in older hypertensive patients

Abstract Background and aims. Arterial hypertension doubles the risk of coronary heart disease, heart and kidney failure, and peripheral arterial disease. Less variation in diurnal ambulatory blood pressure monitoring (ABPM) patterns may affect mortality outcome. Therefore, as hypertension occurs in over 95% of older subjects, the prognostic value of dipping status in older hypertensive patients will be assessed. Method. The retrospective study group consisted of 170 hypertensive patients, aged 75–84 years, enrolled in the years 2005 to 2007. Baseline measures included 24-h ABPM. Diurnal index and dipping status was calculated and stratified the group into dippers (40 patients, 23.5%), non-dippers (65 patients, 38.2%) and reverse-dippers (65 patients, 38.2%). Results. During a 5-year observation, after baseline we have observed 69 deaths (40.9%) from the whole group of 170 patients with 23 (35.4%) being non-dippers and 36 (55.4%) reverse-dippers. There were significant differences between the groups divided according to diurnal dipping status in survival time, number of recorded deaths and night mean blood pressure. We have identified and confirmed risk factors for the all-cause mortality: age, mean systolic and diastolic blood pressure, diurnal index and dipping status (dipping, non-dipping or reverse-dipping). Conclusion. Reverse-dippers and non-dippers revealed worse prognosis compared with dippers.

Regional differences of vasodilatation and vasomotion response to local heating in human cutaneous microcirculation

BACKGROUND The aim of this study was to evaluate the vasodilatation and vasomotion response to local heating in the cutaneous microcirculation of the ankle, dorsum of foot and forearm. Recently, it has been suggested that this response differs between the forearm and the leg. PROBANDS AND METHODS Twenty-nine young healthy adults were recruited. They underwent measurement by laser Doppler flowmetry (LDF) in three sites of the body (ankle, dorsum of foot, forearm). Percentage change of the median flow of the skin before and after provocation and normalised perfusion flow to maximal dilation (cutaneous vascular conductance--CVC % Max) during short provocation test were monitored. Spectral analysis of laser Doppler flowmetry signals was performed using the fast Fourier transform algorithm. RESULTS Significant differences were found in CVC % Max between ankle/dorsum (45.18±6.38% Max vs. 51.24±6.87% Max, respectively; p<0.05) and between ankle/forearm (45.18±6.38% Max vs. 54.49±5.37% Max, respectively; p<0.05). Percentage change of flux after provocation has revealed significant differences between ankle/dorsum (394.1±204.5% vs. 577.4±273.5%, respectively; p<0.05) and ankle/forearm (394.1±204.5% vs. 637.1±324.7%, respectively; p<0.05). Total spectral activity of vasomotion has differed between ankle/dorsum and ankle/forearm: 69.59 [49.58-96.04] vs. 93.01 [73.15-121.8] (p<0.05) and 69.59 [49.58-96.04] vs. 107.5 [80.55-155.8] (p<0.05), respectively. CONCLUSIONS Cutaneous microcirculation exhibits regional differences. Significant variability of function between ankle and dorsum of foot suggests that leg microcirculation is not uniform.