Relationship of para- and perirenal fat and epicardial fat with metabolic parameters in overweight and obese subjects.

BACKGROUND: The accumulation of visceral body fat, has been shown to be associated with higher risk of metabolic and cardiovascular disease. This study was addressed to examine whether para- and perirenal fat thickness and epicardial fat thickness were correlated with anthropometric- and cardiometabolic risk factors. METHODS: A cohort of 102 uncomplicated overweight and obese patients was examined. BMI, waist circumference, blood pressure, fasting insulin, glucose, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol serum levels, and insulin resistance (assessed by HOMAIR) were measured. Para- and perirenal fat thickness (PUFT) and epicardial fat thickness (EUFT) were measured by ultrasounds. RESULTS: PUFT was positively correlated with BMI (p < 0.001), waist circumference (p < 0.001), insulin (p < 0.001), HOMAIR (p < 0.001), triglycerides (p < 0.05), systolic (p < 0.05) and diastolic (p < 0.05) blood pressure, and negatively correlated with HDL-cholesterol (p < 0.01). EUFT was positively associated with age (p < 0.01), BMI (p < 0.001), waist circumference (p < 0.001), systolic (p < 0.01) and diastolic (p < 0.001) blood pressure, and LDL-cholesterol (p < 0.05). A multivariate analysis by multiple linear regression was performed, and the final model showed a direct association of waist circumference with both PUFT and EUFT, a correlation of PUFT with HOMAIR (positive) and HDL-cholesterol (negative), and a direct association of EUFT (both long axis and short axis) with LDL-cholesterol. All these correlations were independent of other anthropometric, metabolic and hemodynamic parameters. CONCLUSIONS: This study shows that accumulation of central fat in apparently healthy overweight and obese subjects is associated to a simultaneous increase of pararenal, perirenal and epicardial fat. Moreover, it shows that only para- and perirenal fat is independently associated to insulin resistance and lower HDL-cholesterol, and only epicardial fat is independently associated to higher LDL cholesterol. Level of evidence Level V, cross-sectional descriptive study.

Para- and perirenal ultrasonographic fat thickness is associated with 24-hours mean diastolic blood pressure levels in overweight and obese subjects.

BACKGROUND: Renal sinus fat (RSF) has been recognized as a risk factor for arterial hypertension. This study was addressed to examine whether also para- and perirenal fat accumulation is associated to higher 24-h mean systolic (SBP) and/or diastolic blood pressure (DBP) levels in overweight and obese subjects. METHODS: A cohort of 42 overweight and obese patients, 29 women and 13 men, aged 25-55 years, not treated with any kind of drug, was examined. Body mass index (BMI), waist circumference (WC), fasting insulin and glucose serum levels, insulin resistance (assessed by using the homeostasis model assessment [HOMAIR]), and 24-h aldosterone urine levels were measured. Ambulatory blood pressure monitoring (ABPM) was measured with 15 min intervals from 7.0 a.m. to 11.0 a.m. and with 30 min intervals from 23.0 to 7.0 for consecutive 24 h, starting from 8:30 AM. Measurement of para- and perirenal fat thickness was performed by ultrasounds by a duplex Doppler apparatus. RESULTS: Para- and perirenal ultrasonographic fat thickness (PUFT) was significantly and positively correlated with WC (p < 0.01), insulin (p < 0.01), HOMAIR (p < 0.01), and 24-h mean DBP levels (p < 0.05). 24-h mean DBP was also significantly and positively correlated with 24-h aldosterone urine concentrations (p < 0.001). A multivariate analysis by multiple linear regression was performed; the final model showed that the association of 24-h mean DBP as dependent variable with PUFT (multiple R = 0.34; p = 0.026) and daily aldosterone production (multiple R = 0.59; p = 0.001) was independent of other anthropometric, hormone and metabolic parameters. DISCUSSION AND CONCLUSIONS: This study shows a positive independent association between PUFT and mean 24-h diastolic blood pressure levels in overweight and obese subjects, suggesting a possible direct role of PUFT in increasing daily diastolic blood pressure.

Arterial hypertension in obesity: relationships with hormone and anthropometric parameters.

BACKGROUND: Obesity has been recognized as an independent risk factor for arterial hypertension. DESIGN: This study was addressed to identify parameters predictive of 24-h mean systolic and/or diastolic blood pressure levels in obesity. METHODS: A cohort of 180 euthyroid overweight and obese patients, 79 women and 101 men, aged 20-63 years, normotensive (n = 62) or with recently developed hypertension (n = 118), and never treated with antihypertensive drugs, was examined. Waist circumference, fasting insulin, thyroid stimulating hormone (TSH), free thyroxine (FT) FT(3), FT(4), glucose, and lipid (cholesterol, high-density lipoprotein cholesterol and triglyceride) serum concentrations, and 24-h urinary aldosterone and catecholamines were measured. Ambulatory blood pressure monitoring (ABPM) was performed and hypertension was confirmed when 24-h mean systolic blood pressure was ≥125 mmHg and/or 24-h mean diastolic blood pressure was ≥80 mmHg, according to the 2007 European Society of Hypertension and European Society of Cardiology Practice Guidelines for the Management of Arterial Hypertension. RESULTS: 24-h noradrenaline (p < 0.01) and adrenaline (p < 0.05) levels were higher in hypertensive than in normotensive subjects. The odds ratio (OR) was determined by several univariate and multivariate logistic regression analyses to evaluate the predictive factors of high 24-h blood pressure mean values. When subjects with high systolic and/or high diastolic blood pressure levels (n = 118) were compared to individuals with normal systolic and diastolic blood pressure levels (n = 62), multivariate analysis showed an independent association of hypertension with male gender and 24-h noradrenaline levels. When subjects with high systolic blood pressure levels (n = 108) were compared with those with normal systolic blood pressure levels (n = 72), multivariate analysis showed an independent association of high systolic blood pressure with noradrenaline levels. Lastly, when subjects with high diastolic blood pressure levels (n = 87) were compared with those with normal diastolic blood pressure levels (n = 93), multivariate analysis showed an independent negative association between high diastolic blood pressure and body mass index. CONCLUSIONS: the present study shows that diastolic blood pressure is independently and negatively associated with body mass index in normotensive or with recently discovered hypertension overweight and obese subjects, and never treated with antihypertensive drugs. These results suggest that obesity per se is responsible for a decrease in diastolic blood pressure before hypertensive state becomes stable. This study also confirms that male gender and daily noradrenaline production contribute to hypertension, and to higher systolic blood pressure levels in particular.

Independent Relationship of Osteocalcin Circulating Levels with Obesity, Type 2 Diabetes, Hypertension, and HDL Cholesterol.

BACKGROUND: Osteocalcin, a protein synthesized by osteoblasts during the bone formation phase of bone remodeling, is used as a biomarker for the bone production process, and its serum levels are positively correlated with bone mineral density during treatment with anabolic bone drugs for osteoporosis. Higher fat mass has been shown to be a risk factor for osteoporosis and fragility fractures and body fat and bone interplay through several adipokines and bone-derived molecules, regulating bone remodeling, adipogenesis, body weight control, and glucose homeostasis. AIM: The aim of this study was to evaluate the relationship between total osteocalcin levels and obesity, hypertension and type 2 diabetes. METHODS: The present study was performed in a cohort of 298 patients including a) 121 overweight and obese patients, unaffected by hypertension or type 2 diabetes, b) 129 subjects affected by hypertension and not by type 2 diabetes, and c) 48 subjects affected by both hypertension and type 2 diabetes. No subject of the group of overweight and obese patients was taking any kind of drug. All patients affected by hypertension, with or without type 2 diabetes, were taking drugs for hypertension. Examining only patients affected by type 2 diabetes (n: 48), 43 (90% of all) were taking drugs to reduce blood glucose levels, 26 (54% of all) were taking drugs to reduce cholesterol levels (statins and/or ezetimide, etc), and 4 (8% of all) were taking ω-3 for hypertriglyceridemia. Each patient was evaluated for anthropometric measurements as well as for serum osteocalcin and uric acid, and plasma glucose, HbA1c, and lipid determination. RESULTS: Osteocalcin levels were significantly and negatively associated with BMI, waist circumference, and HbA1c, and significantly and positively correlated with HDL-cholesterol and systolic blood pressure in the whole population. Osteocalcin levels did maintain an independent negative association with BMI, and HbA1c, and positive association with HDL cholesterol and systolic blood pressure when a multiple regression analyses was performed by considering osteocalcin levels as the dependent variable and BMI, systolic blood pressure, HbA1c, and HDL cholesterol as independent variables. When age was included in the analyses among the independent variables, osteocalcin levels maintained an independent association with BMI, systolic blood pressure, HbA1c, and HDL cholesterol, but not with age. DISCUSSION AND CONCLUSION: The results of the present study seem to suggest that patients with obesity and type 2 diabetes are at higher risk of lower osteocalcin levels and bone formation, whereas higher HDLcholesterol levels and systolic blood pressure seem to be associated to higher osteocalcin production.

Higher Waist Circumference, Fasting Hyperinsulinemia And Insulin Resistance Characterize Hypertensive Patients With Impaired Glucose Metabolism.

UNLABELLED: Hypertensive patients are at higher risk of pre-diabetes (impaired fasting glucose IFG and impaired glucose tolerance IGT) and type 2 DM. This study was done to examine whether some general, anthropometric, hormone, and metabolic parameters are different between subjects with normal and impaired glucose metabolism (IGM) in hypertensive subjects, thus possibly identifying some variable characterizing glucose metabolism derangement in these patients. A cohort of 134 hypertensive patients, 55 women and 79 men, aged 37-70 years, were examined. IGM patients were considered those showing IFG and/or IGT or type 2 DM after an oral glucose tolerance test (OGTT), and/or HbA1c > 48 mmol/l (6.5%) and/or glucose levels >155 mg/dL after 1 hour of the OGTT. Body mass index (BMI), waist circumference, and fasting insulin, TSH, FT3, FT4, glucose, and lipid (cholesterol, HDL-cholesterol and triglycerides) plasma concentrations were measured. Insulin resistance was also assessed by the homeostasis model assessment (HOMAIR). RESULTS: Waist circumference (p < 0.05), fasting glucose (p < 0.05) and insulin levels (p < 0.05) and HOMAIR (p < 0.05) were significantly higher in patients with IGM than in control group. All other investigated parameters, as well as the number of antihypertensive drugs per single patient, were not different between the two groups. CONCLUSIONS: The present study, performed in a selected population of hypertensive subjects, shows that derangement of glucose metabolism is associated to central fat accumulation, hyperinsulinemia and insulin resistance.

Obesity and heart failure.

Epidemiological studies have recently shown that obesity, and abdominal obesity in particular, is an independent risk factor for the development of heart failure (HF). Higher cardiac oxidative stress is the early stage of heart dysfunction due to obesity, and it is the result of insulin resistance, altered fatty acid and glucose metabolism, and impaired mitochondrial biogenesis. Extense myocyte hypertrophy and myocardial fibrosis are early microscopic changes in patients with HF, whereas circumferential strain during the left ventricular (LV) systole, LV increase in both chamber size and wall thickness (LV hypertrophy), and LV dilatation are the early macroscopic and functional alterations in obese developing heart failure. LV hypertrophy leads to diastolic dysfunction and subendocardial ischemia in obesity, and pericardial fat has been shown to be significantly associated with LV diastolic dysfunction. Evolving abnormalities of diastolic dysfunction may include progressive hypertrophy and systolic dysfunction, and various degrees of eccentric and/or concentric LV hypertrophy may be present with time. Once HF is established, overweight and obese have a better prognosis than do their lean counterparts with the same level of cardiovascular disease, and this phenomenon is called "obesity paradox". It is mainly due to lower muscle protein degradation, brain natriuretic peptide circulating levels and cardio-respiratory fitness than normal weight patients with HF.

Abdominal obesity is characterized by higher pulse pressure: possible role of free triiodothyronine.

Objective. This study examined whether obesity is characterized by higher 24 h mean pulse pressure (24 h mean SBP-24 h mean DBP) and whether free thyroid hormones (FT(3) and FT(4)) have a relationship with 24 h mean pulse pressure. Methods. A total of 231 euthyroid overweight and obese patients, 103 women and 128 men, aged 18-68 yrs, normotensive (n = 69) or with recently developed hypertension (n = 162), never treated with antihypertensive drugs, were investigated. Fasting insulin, TSH, FT(3), FT(4), glucose, and lipid serum concentrations were measured. Waist circumference was measured as an indirect parameter of central fat accumulation. Ambulatory blood pressure monitoring (ABPM) was performed. Results. 24 h mean pulse pressure (PP) showed a significant positive correlation with BMI (P < 0.001), waist circumference (P < 0.001), and FT(3) (P < 0.001) and insulin serum levels (P < 0.05). When a multivariate analysis was performed, and 24 h PP was considered as the dependent variable, and waist circumference, FT(3), insulin, male sex, and age as independent parameters, 24 h mean PP maintained a significant association only with waist circumference (P < 0.001) and FT(3) levels (P < 0.05). Conclusion. Our results suggest that FT(3) per se may contribute to higher pulse pressure in obese subjects.

Investigation of platelet aggregation inhibitory activity by phenyl amides and esters of piperidinecarboxylic acids.

A series of anilides and phenyl esters of piperidine-3-carboxylic acid (nipecotic acid) were synthesized and tested for the ability to inhibit aggregation of human platelet rich-plasma triggered by adenosine 5'-diphosphate (ADP) and adrenaline. As a rule, amides were about two times more active than the corresponding esters, and derivatives bearing substituents at the para position of the phenyl ring were significantly more active than the meta-substituted ones. Among the tested compounds, 4-hexyloxyanilide of nipecotic acid (18a) was found to be the most active one, its IC(50) value being close to that of the most active bis-3-carbamoylpiperidines reported in literature (ca. 40 micro M) and aspirin (ca. 60 microM) in ADP- and adrenaline-induced aggregation, respectively. Compared with the isomeric 4-hexyloxyanilides of piperidine-2-carboxylic (pipecolinic) and piperidine-4-carboxylic (isonipecotic) acids, compound 18a showed higher activity, and a Hansch-type quantitative structure-activity relationship (QSAR) study highlighted lipophilicity and increase in electron density of the phenyl ring as the properties which mainly increase the antiplatelet activity (r(2)=0.74, q(2)=0.64). The interaction of nipecotoyl anilides with phosphatidylinositol, a major component of the inner layer of the platelet membranes, was investigated by means of flexible docking calculation methods to give an account of a key event underlying their biological action.