OBJECTIVE:Pulse pressure (PP), is a simple measure of arterial stiffness. Several studies have shown that PP increases the risk of cardiovascular (CV) events but they were limited to clinic measure, ...mostly performed on individuals with high CV risk. Furthermore few studies reported PP-related risk of morbidity and mortality separately for genders.
DESIGN AND METHOD:3200 subjects, stratified for sex and decades of ages, were randomly selected to be representative of the general population of Monza (Northern Italy). In each subject we performed the following mesurements1) Clinic (C) Systolic (S) Blood Pressure (BP) and Diastolic (D) BP (sphygmomanometer), 2) Home SBP and DBP (Philips HP 5331), 3) Ambulatory (24 h) SBP and DBP (Spacelabs 90207), 4) Body Mass Index (BMI), 5) Blood Glucose and Serum Cholesterol. Each subject was followed for 12 years, during which all deaths were collected and classified by ICD-X codes as being a CV (ICD-X I-0 to I-99) or non CV death. Non-fatal CV events were identified by hospital diagnosis also using ICD-X codes and validated on the hospital clinical records.
RESULTS:The complete data set was obtained in 2045 subjects. PP was calculated as difference between SBP and DBP. Office, home and 24 h blood pressures were significantly higher in individuals who experienced a CV event or died during follow-up. Clinic, 24 h and Daytime PP were independent predictors of CV events after adjustment for main demographic and clinical parameters in the whole study population (HR 1.24, CI 1.03–1.49; HR 1.17, CI 1.01–1.36; HR 1.2, CI 1.03–1.39, respectively; p < 0.05 for all). Nighttime PP was an additional independent predictor in men (HR 1.23, CI 1.03–1.47, p < 0.05). None of measured PP (Clinic, Home, 24 h, Day- and Nighttime) was predictor of CV events in women. None of calculated PP was predictor of all-cause mortality in general population and in both genders.
CONCLUSIONS:Clinic and 24 h, but not home, PP represent a predictor of CV events in general population and in its male fraction. In females PP does not increase risk of CV events. All-cause death is not predicted by any of the PP measured.
In prostate adenocarcinoma, the dissection of the expression behaviour of the eukaryotic elongation factors (eEF1A1/2) has not yet fully elucidated.
The EEF1A1/A2 expressions were investigated by ...real-time PCR, western blotting (cytoplasmic and cytoskeletal/nuclear-enriched fractions) and immunofluorescence in the androgen-responsive LNCaP and the non-responsive DU-145 and PC-3 cells, displaying a low, moderate and high aggressive phenotype, respectively. Targeted experiments were also conducted in the androgen-responsive 22Rv1, a cell line marking the progression towards androgen-refractory tumour. The non-tumourigenic prostate PZHPV-7 cell line was the control.
Compared with PZHPV-7, cancer cells showed no major variations in EEF1A1 mRNA; eEF1A1 protein increased only in cytoskeletal/nuclear fraction. On the contrary, a significant rise of EEF1A2 mRNA and protein were found, with the highest levels detected in LNCaP. Eukaryotic elongation factor 1A2 immunostaining confirmed the western blotting results. Pilot evaluation in archive prostate tissues showed the presence of EEF1A2 mRNA in near all neoplastic and perineoplastic but not in normal samples or in benign adenoma; in contrast, EEF1A1 mRNA was everywhere detectable.
Eukaryotic elongation factor 1A2 switch-on, observed in cultured tumour prostate cells and in human prostate tumour samples, may represent a feature of prostate cancer; in contrast, a minor involvement is assigned to EEF1A1. These observations suggest to consider EEF1A2 as a marker for prostate cell transformation and/or possibly as a hallmark of cancer progression.
The benefits of exercise and behavioural recommendations in gestational diabetes mellitus (GDM) are controversial. In a randomized trial with a 2×2 factorial design, we examined the effect of ...exercise and behavioural recommendations on metabolic variables, and maternal/neonatal outcomes in 200 GDM patients. All women were given the same diet: group D received dietary recommendations only; group E was advised to briskly walk 20‐min/day; group B received behavioural dietary recommendations; group BE was prescribed the same as B + E. Dietary habits improved in all groups. In a multivariable regression model, fasting glucose did not change. Exercise, but not behavioural recommendations, was associated with the reduction of postprandial glucose (p < 0001), glycated haemoglobin (HbA1c; p < 0.001), triglycerides (p = 0.02) and C‐reactive protein (CRP; p < 0.001) and reduced any maternal/neonatal complications (OR = 0.50; 95%CI=0.28–0.89;p = 0.02). In GDM patients a simple exercise programme reduced maternal postprandial glucose, HbA1c, CRP, triglycerides and any maternal/neonatal complications, but not fasting glucose values.
OBJECTIVE:Masked (MUCH) and white coat uncontrolled hypertension (WUCH) are more and more frequently investigated for their long-term prognostic significance Classification is usually made by a ...single set of office and out-of-office blood pressure (BP) measurements during the treatment period. To evaluate the long-term reproducibility of MUCH and WUCH, an information crucial for determining the long-term prognostic impact of these conditions.
DESIGN AND METHOD:Reproducibility of MUCH and WUCH was assessed in 1664 hypertensive patients recruited for the ELSA study treated with atenolol or lacidipine (+/– additional drugs) during a 4-year period. Office and 24-hour BP was measured at baseline and every year during treatment, allowing repeated classification of either condition.
RESULTS:After 1 year of treatment 21.1% and 17.8% of the patients were classified as MUCH and WUCH, respectively. For both conditions the prevalence was similar in the following years, although with a large change in patients composition because only about 1/3 of patients classified as MUCH or WUCH at one set of office and ambulatory BP measurements maintained the same classification at a subsequent set of measurements. In only 4.5% and 6.2% MUCH and WUCH persisted throughout the treatment period. MUCH and WUCH reproducibility was worse than that of patients showing control or lack of control of both office and ambulatory BP.
CONCLUSIONS:Both MUCH and WUCH display a poor reproducibility over time. This should be taken into account in studies assessing the long-term prognostic value of these conditions based on only one set of BP measurements.
OBJECTIVE:The ESC/ESH Guidelines for hypertension issued in 2018 identify resting heart rate (HR) values greater than 80 beats/minute as predictors of cardiovascular risk, with the undocumented ...evidence that this detection might represent the occurrence of a sympathetic cardiovascular overdrive. In the present study we tested this hypothesis throughout the use of direct and indirect markers of sympathetic neural function.
DESIGN AND METHOD:In 167 untreated and uncomplicated mild-to moderate essential hypertensives recruited for different investigations and aged 51.8 ± 3.2 years (mean ± SEM) without other cardiovascular or non-cardiovascular disease, we measured clinic and ambulatory blood pressure (BP), HR (EKG), venous plasma norepinephrine (NE, HPLC assay) and efferent postganglionic muscle sympathetic nerve traffic (MSNA, microneurography). We then subdivided the study population in 2 groups according to HR values <= or >80 beats/minute.
RESULTS:Sixty eight patients displayed resting HR > 80 beats/minute while the remaining 99 below this threshold value, the 2 groups showing superimposable age values and gender distribution. Body mass index, clinic and ambulatory BP were similar in the 2 groups this being the case also for LVMI and metabolic variables. In contrast MSNA values were significantly greater (P < 0.02) in the former than in the latter group both when expressed as bursts incidence over time (49.2 ± 1.8 vs 39.5 ± 1.4 bs/min) and when corrected for HR (60.7 ± 3.0 vs 51.4 ± 2.5 bs/100 hb). NE showed a tendency to be greater in the former group without achieving, however, statistical significance. In the whole population there was a significant direct relationship between MSNA and HR values (r = 0.61, P < 0.01)
CONCLUSIONS:Thus hypertensive patients displaying HR > 80 beats/minute are characterized by a marked sympathetic overdrive, particularly when direct adrenergic markers are employed. This finding suggests that cardiac and peripheral sympathetic activation may participate at the increased cardiovascular risk detected in this group of patients.
OBJECTIVE:Nerve traffic recordings (MSNA) have shown that sympathetic activation may occur in obese individuals (O). However, the small sample size of the available studies, presence of ...comorbidities, including sleep apnea, heterogeneity of the patients examined as well as presence of confounders represented major weaknesses not allowing to draw definite conclusions. This is particularly the case for overweight condition.
DESIGN AND METHOD:The present metanalysis evaluated 1167 O recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in O of different clinical severity, excluding as concomitant conditions hypertension, sleep apnea and other comorbidities.Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as venous plasma norepinephrine and heart rate (NE and HR, respectively), anthropometric variables, such as body mass index (BMI), waist-hip ratio (WHR) and metabolic variables.
RESULTS:Compared to normoweight MSNA was significantly greater after adjustments for confounders in overweight and more so in O (37.0 ± 4.1 vs 43.2 ± 3.5 and 50.4 ± 5 bs/100 hb, P < 0.01). MSNA was directly and significantly related to BMI and WHR (r = 0.41 and r = 0.64, P < 0.04 and <0.01 respectively), clinic blood pressure (r = 0.68, P < 0.01), total cholesterol, LDL cholesterol, triglycerides and glucose (r = 0.91, 0.94, 0.80 and 0.59, respectively, P < 0.01). No significant correlation was found between anthropometric indices and plasma insulin, HOMA index and plasma leptin. No correlation was found between MSNA and HR and NE.
CONCLUSIONS:Both O and overweight patients are characterized by sympathetic overactivity which mirrors the increase in BMI and WHR and the severity of the obese state and reflects metabolic alterations, with the exclusion of insulin. Neither HR nor NE appear to represent in O and in overweight faithful mirrors of the occurring sympathetic activation.
OBJECTIVE:Over the last decades the prevalence of obesity in children and adolescents has increased worldwide. This fact affects health expectancy and quality of life and then, assessment of ...cardiovascular risk factors has been emphasized. Among cardiovascular risk factors in adults, the relevance of cardiorespiratory fitness has been highlighted by the American Heart Association (AHA, Circulation 2016).To assess the cardiorespiratory fitness and its relationship with the cardiac autonomic neural activity, a marker of early cardiometabolic risk, in youths with abnormally increased body weight.
DESIGN AND METHOD:Sixty-four overweight and obese subjects, 9 to 17 years, of both sexes, stratified according to the international body mass index cut-off, were enrolled. Continuous electrocardiogram was recorded during 15 minutes in resting and supine conditions, and afterwards heart rate variability was analysed in the time and frequency domain as well as non-linear dynamics. In addition, cardiorespiratory fitness in effort conditions was assessed (VO2peak).
RESULTS:Among the obese youths, cardiorespiratory fitness was the lowest in severe obese despite that no significant differences were observed regarding heart rate nor heart rate variability in time and frequency domain. A positive and significant relationship, independent of the degree of obesity, pubertal stage and breathing rate under resting conditions, were observed between cardiorespiratory fitness (assessed by VO2peak) and sympatho-vagal balance, estimated by standard deviation of the NN interval (SDNNr = 0.268, p < 0.05) and the long term variation using the Poincaré plot (PS1r = 0.275, p < 0.05; PS2 r = 0.273, p < 0.05).
CONCLUSIONS:The key finding of the present study was the presence of a link between cardiorespiratory fitness and cardiac autonomic nervous system activity, independent of the degree of obesity. This emphasises that cardiorespiratory fitness can be a relevant tool in the assessment of early cardiovascular risk in obese youths.
OBJECTIVE:In the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, clinical, metabolic variables as well as office, home, and ambulatory blood pressure (BP) values were measured ...contemporaneously at baseline and after a ten-year period of follow-up, which allowed us to assess the value of selective and combined elevation of these BPs in predicting new onset metabolic syndrome (MetS).
DESIGN AND METHOD:The present analysis included 1,182 participants without MetS at baseline, as defined by the APT III criteria. Based on office, 24-hour ambulatory BP and home values, subjects were divided into 4 groupsnormal, with coat hypertension (WCH), masked hypertension (MH); and sustained hypertension (SH).
RESULTS:As compared to subjects with in-office and out-of-office BP normality a greater age- and gender-adjusted incidence of new onset Mets was observed in WCH (OR = 2.03, CI:1,21-3.41, p = 0.007), MH (OR = 2.55, CI:1.26–5.17; p = 0.009) and SH (OR = 2.28, CI:1.43–3.99, p = 0.0009) when out-of-office BP was defined by ambulatory criteria. This was not the same when out-of-office BP was based on home criteria, as only the WCH group showed a significant greater OR risk (2.16, CI1.28–3.63, p = 0.003).
CONCLUSIONS:Our study provides evidence that isolated or combined BP elevations when identified by office/ambulatory measurements, carry an increase in risk of new onset MetS, while classifying the population by combining office/home BPs only WCH is associated with a greater risk of incident MetS. In a clinical perspective, a comprehensive evaluation of BP status based on office/ambulatory measurements may substantially improve the risk stratification of new onset MetS and to activate measures for its prevention
OBJECTIVE:Studies addressing the association between a reduced drop of heart rate (HR) at night with subclinical organ damage and cardiovascular events in the general population are scanty. We ...evaluated this issue in subjects enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study.
DESIGN AND METHOD:At entry 2,021 subjects underwent diagnostic tests including laboratory investigations, 24-h ambulatory blood pressure (BP) monitoring and echocardiography. Participants were followed from the initial medical visit for a time interval of 148 ± 27 months. To explore the association of circadian HR rhythm and outcomes participants were classified in the primary analysis according to quartiles of nocturnal HR decrease. In secondary analyses the population was also classified according non-dipping nocturnal HR (defined as a drop in average HR at night lower than 10% compared to day-time values) and next in four categories(1) BP/HR dipper, 2) BP/HR non dipper, 3) HR dipper/BP non dipper, 4) HR non dipper/BP dipper).
RESULTS:A flattened circadian HR rhythm (i.e. lowest quartile of night-time HR dip) was independently associated to left atrial (LA) enlargement, but not to left ventricular hypertrophy; moreover, it was predictive of fatal and non-fatal cardiovascular events, independently of several confounders (hazard ratio 1.8, CI1.13–2.86, p < 0.01 vs highest quartile).
CONCLUSIONS:A blunted dipping of nocturnal HR is associated to preclinical cardiac damage in terms of LA enlargement and is predictive cardiovascular morbidity and mortality in the general population.
OBJECTIVE:The association between pre-hypertension (pre-HTN) and subclinical cardiac organ damage is not well defined. We performed a systematic meta-analysis of echocardiographic studies in order to ...provide a comprehensive information on cardiac structural and functional changes in untreated pre-HTN subjects.
DESIGN AND METHOD:Studies were identified by crossing the following search termspre-hypertension, high normal blood pressure, heart, left ventricular hypertrophy, left ventricular function, diastolic function, left atrial size, aortic root size, echocardiography.
RESULTS:A total 73,556 subjects (44,170 normotensive, 17,314 pre-HTN, and 12,072 HTN individuals) of both genders were included in 20 studies. Left ventricular (LV) mass index was greater in pre-HTN than in normotensives (standard means difference SMD0.32 ± 0.07, p < 0.001). Mitral E/A ratio was lower (SMD−0.34. ± 0.05,p < 0.001), E/e’ ratio (SMD0.26 ± 0.02, p < 0.001) and left atrium (LA) diameter higher (SMD0.55 ± 0.02, p < 0.001) in pre-HTN than in normotensive counterparts. HTN subjects showed a greater LV mass index (SMD0.27 ± 0.03, p < 0.001), reduced E/A (SMD−0.38 ± 0.08, p < 0.001), increased E/e’ ratio (SMD0.38 ± 0.09, p < 0.001), and LA diameter (SMD0.31 ± 0.12, p < 0.001) than pre-HTN subjects
CONCLUSIONS:Our meta-analysis shows that alterations in cardiac structure and function in pre-HTN subjects are intermediate between normotensive and HTN individuals. These findings reinforce the view that pre-HTN should not be longer considered a benign entity.
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