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Background: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort., Methods and Results: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P <0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P =0.004) and 1.150 (95% CI, 1.021-1.295, P =0.02), respectively., Conclusions: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Background and Aim: Over 80% (365/454) of the nation's centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment., Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules., Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20-1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02-1.17), test-all policy (IRR 5.94, 95% CI 3.36-10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001-1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94-0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers., Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center's testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.

Background: . The electrocardiographic (ECG) changes which may occur during hospitalization for COVID-19 have not yet been comprehensively assessed., Patients and Methods: . We examined 50 patients admitted to hospital with proven COVID-19 pneumonia. At entry, all patients underwent a detailed clinical examination, 12-lead ECG, laboratory tests and arterial blood gas test. ECG was also recorded at discharge and in case of worsening clinical conditions., Results: . Mean age of patients was 64 years and 72% were men. At baseline, 30% of patients had ST-T abnormalities, and 33% had left ventricular hypertrophy. During hospitalization, 26% of patients developed new ECG abnormalities which included atrial fibrillation, ST-T changes, tachy-brady syndrome, and changes consistent with acute pericarditis. One patient was transferred to intensive care unit for massive pulmonary embolism with right bundle branch block, and another for non-ST segment elevation myocardial infarction. Patients free of ECG changes during hospitalization were more likely to be treated with antiretrovirals (68% vs 15%, p = 0.001) and hydroxychloroquine (89% vs 62%, p = 0.026) versus those who developed ECG abnormalities after admission. Most measurable ECG features at discharge did not show significant changes from baseline (all p>0.05) except for a slightly decrease in Cornell voltages (13±6 vs 11±5 mm; p = 0.0001) and a modest increase in the PR interval. The majority (54%) of patients with ECG abnormalities had 2 prior consecutive negative nasopharyngeal swabs. ECG abnormalities were first detected after an average of about 30 days from symptoms' onset (range 12-51 days)., Conclusions: . ECG abnormalities during hospitalization for COVID-19 pneumonia reflect a wide spectrum of cardiovascular complications, exhibit a late onset, do not progress in parallel with pulmonary abnormalities and may occur after negative nasopharyngeal swabs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Aims: This joint document of the Italian Diabetes Society and the Italian Society of Nephrology reviews the natural history of diabetic kidney disease (DKD) in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents., Data Synthesis: Recent epidemiological studies have disclosed a wide heterogeneity of DKD. In addition to the classical albuminuric phenotype, two new albuminuria-independent phenotypes have emerged, i.e., "nonalbuminuric renal impairment" and "progressive renal decline", suggesting that DKD progression toward end-stage kidney disease (ESKD) may occur through two distinct pathways, albuminuric and nonalbuminuric. Several biomarkers have been associated with decline of estimated glomerular filtration rate (eGFR) independent of albuminuria and other clinical variables, thus possibly improving ESKD prediction. However, the pathogenesis and anatomical correlates of these phenotypes are still unclear. Also the management of hyperglycemia in patients with type 2 diabetes and impaired renal function has profoundly changed during the last two decades. New anti-hyperglycemic drugs, which do not cause hypoglycemia and weight gain and, in some cases, seem to provide cardiorenal protection, have become available for treatment of these individuals. In addition, the lowest eGFR safety thresholds for some of the old agents, particularly metformin and insulin secretagogues, have been reconsidered., Conclusions: The heterogeneity in the clinical presentation and course of DKD has important implications for the diagnosis, prognosis, and possibly treatment of this complication. The therapeutic options for patients with type 2 diabetes and impaired renal function have substantially increased, thus allowing a better management of these individuals.

Competing Interests: Declaration of Competing Interest None.

Background and objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Among extra-pulmonary manifestations of COPD, atrial fibrillation (AF) is commonly observed in clinical practice. The coexistence of COPD and AF significantly affects the risk of cardiovascular morbidity and mortality. Nonetheless, the mechanisms explaining the increased risk of vascular events and death associated to the presence of COPD in AF are complex and not completely understood. We analyzed data from an Italian network database to identify markers and mediators of increased vascular risk among subjects with AF and COPD. Materials and Methods: Cross-sectional analysis of the Umbria Atrial Fibrillation (Umbria-FA) Registry, a multicenter, observational, prospective on-going registry of patients with non-valvular AF. Of the 2205 patients actually recruited, 2159 had complete clinical data and were included in the analysis. Results: the proportion of patients with COPD was 15.6%. COPD patients had a larger proportion of permanent AF when compared to the control group (49.1% vs. 34.6%, p < 0.0001) and were more likely to be obese and current smokers. Other cardiovascular risk factors including chronic kidney disease (CKD), peripheral artery disease and subclinical atherosclerosis were more prevalent in COPD patients (all p < 0.0001). COPD was also significantly associated with higher prevalence of previous vascular events and a history of anemia (all p < 0.0001). The thromboembolic and bleeding risk, as reflected by the CHA 2 DS 2 VASc and HAS-BLED scores, were higher in patients with COPD. Patients with COPD were also more likely to have left ventricular (LV) hypertrophy at standard ECG than individuals forming the cohort without COPD ( p = 0.018). Conclusions: AF patients with COPD have a higher risk of vascular complications than AF patients without this lung disease. Our analysis identified markers and mediators of increased risk that can be easily measured in clinical practice, including LV hypertrophy, CKD, anemia, and atherosclerosis of large arteries.

In patients with hypertension, but without established cardiovascular disease, predictive factors for sudden cardiac death (SCD) remain undefined. We followed for an average of 10.3 years a cohort of 3242 initially untreated hypertensive patients without evidence of coronary or cerebrovascular heart disease at entry. All patients underwent a complete clinical examination which included ECG and 24-hour ambulatory blood pressure monitoring. At entry, the mean age of patients was 50.0 years, 45% were women, and 6.1% had type 2 diabetes mellitus. Average office blood pressure was 154/96 mm Hg, and average 24-hour ambulatory blood pressure was 136/86 mm Hg. Prevalence of left ventricular hypertrophy at ECG was 13.9%. During follow-up, SCD occurred in 33 patients at a rate of 0.10 per 100 patient-years (95% CI, 0.07-0.14). The rate of SCD was 0.07 and 0.30 per 100 patient-years, respectively, in the cohort of patients without and with ECG left ventricular hypertrophy ( P<0.01). In a multivariable Cox model with Firth penalized maximum bias reduction method for rare outcome events, left ventricular hypertrophy almost tripled the risk of SCD (adjusted hazard ratio, 2.99; 95% CI, 1.47-6.09; P=0.002) after adjustment for age ( P<0.0001), sex ( P=0.019), diabetes mellitus ( P<0.0001), and 24-hour ambulatory pulse pressure ( P=0.036). For each 10 mm Hg increase in 24-hour ambulatory pulse pressure, the risk of SCD increased by 35%. The time-dependent area under the receiver operating characteristic curve was 0.85 (95% CI, 0.74-0.96). We conclude that in patients with hypertension without established cardiovascular disease, age, diabetes mellitus, ECG left ventricular hypertrophy, and 24-hour ambulatory pulse pressure are independent prognostic markers for SCD in the long-term.

Objective: The relative role of office heart rate (HR) and ambulatory HR for predicting major adverse cardiovascular events (MACEs) and mortality is not well known. Aim of this study was to investigate the association of white-coat tachycardia and masked tachycardia with MACE and mortality in hypertensive patients., Methods: We performed 24-h ambulatory blood pressure and HR monitoring in 7602 hypertensive patients (4165 men) aged 52 ± 16 years enrolled in six prospective studies in Italy, Japan, and Australia. Participants were divided into four groups: normal office and normal night-time HRs (N = 5238), white-coat tachycardia (N = 998), masked tachycardia (N = 796), and sustained tachycardia (N = 570). Median follow-up was 5.0 years., Results: In age-and-sex-adjusted Cox model, using the normal HRs group as a reference, white-coat tachycardia was not a significant predictor of excess MACEs or all-cause death. In contrast, both masked tachycardia [hazard ratio, 95% confidence interval (CI); 1.40, 1.11-1.77] and sustained tachycardia (1.86, 1.44-2.40) were associated with risk of excess MACE. In addition, masked tachycardia (hazard ratio, 95% CI; 1.62, 1.14-2.29) but not sustained tachycardia (1.35, 0.83-2.19) was a significant predictor of excess mortality. These relationships held true in multivariable parsimonious Cox models including major risk factors. In these models, masked tachycardia remained an independent predictor of excess MACE (hazard ratio, 95% CI; 1.34, 1.06-1.71) and all-cause mortality (1.68, 1.18-2.41)., Conclusion: The current study confirms that measurement of HR adds to the risk stratification for MACE and mortality and shows that an elevated night-time HR confers an increased mortality risk to hypertensive patients who have normal office HR.

In clinical practice, adherence to drugs and their safety may differ from randomised controlled trial settings. This study was undertaken to investigate the adherence to dabigatran, a direct thrombin inhibitor, and its safety in a real-world setting. We studied a prospective cohort of 114 elderly consecutive patients with non valvular atrial fibrillation (AF) who were treated with dabigatran 150 mg twice-daily (N=39) or 110 mg twice-daily (N=76). These patients were studied at baseline and after an average of 6 months. Mean age was 80 years and 53% were women. At entry, the average CHA2DS2VASc score was 4 and the HAS-BLED score was 2. AF was permanent in 49% of patients, persistent in 30%, paroxysmal in 12% and new-onset in 24%. In the follow-up clinical visit we ascertained vital status, adherence to treatment according to refill prescription orders, and side effects. Adherence was ≥80% in 76.5% of patients. Heartburn, the most frequent adverse effect, was reported by 25 patients (22%). Major and minor bleedings were experienced by 2 (1.8%) and 9 (7.9%) patients, respectively. Permanent discontinuation occurred in 18 patients (16%). The most frequent cause of permanent discontinuation was heartburn (10 patients). This real-life study suggests that safety of dabigatran and adherence to this drug in an elderly cohort of AF patients at high or very high risk of thromboembolism are generally good. Heartburn is the main cause of treatment discontinuation.

Obesity reduces the accuracy of voltage-based electrocardiographic (ECG) criteria for diagnosis of left ventricular (LV) hypertrophy. We developed a new ECG score for diagnosis of LV hypertrophy, defined either by a typical strain pattern or a product of the Cornell voltage (R wave height in lead aVL plus S wave depth in lead V3) by body mass index >604 mm∙kg/m(2). We examined a population of 2,747 untreated hypertensive subjects (mean age 49 ± 11 years) with good quality ECG and echocardiographic tracings. Several traditional ECG criteria for LV hypertrophy were compared with the new score, with echocardiographic LV mass taken as reference. Among the tested criteria, the highest sensitivity combined with specificity was yielded by the new score (sensitivity 36.1%, 95% confidence interval [CI] 32.9 to 39.4; specificity 90.5%, 95% CI 89.1 to 91.8; and accuracy 73.1%, 95% CI 71.5 to 74.8). Prevalence of ECG LV hypertrophy with the new score was 18%. On the basis of comparisons between areas under the receiver operating characteristic curves, the best performance was achieved by the new score with respect to other ECG criteria for LV hypertrophy (all p <0.0001). In conclusion, correction of Cornell voltage by body mass index as a marker of obesity improves the performance of traditional electrocardiography for diagnosis of LV hypertrophy in patients with hypertension., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The objective of this paper is to assess the validity of a linguistically validated version of the Lupus Quality of Life (LupusQoL(©)) in Italian patients affected by systemic lupus erythematosus (SLE)., Methods: Consecutive SLE patients completed the Italian version of the LupusQoL(©) and the Short Form (SF)-36. Disease activity was evaluated by the SLE disease activity Index-2000 (SLEDAI-2 K), and chronic damage by the Systemic Lupus International Collaborating Clinics/American College Rheumatology (ACR) Damage Index score (SDI). Internal consistency and test-retest reliability, convergent and discriminant validity were examined. Factor analysis with varimax rotation was performed., Results: A total of 117 Italian SLE patients (M:F 13:104; mean age 40.6 ± 11.6 years, mean disease duration 127.5 ± 94.1 months) were recruited into the study. The Italian version of the LupusQoL(©) demonstrated substantial evidence of convergent validity in these patients when compared with equivalent items of the SF-36. In addition, the LupusQoL(©) discriminated between patients with different degrees of disease activity as measured by the SLEDAI-2 K. SLE patients with higher disease activity (SLEDAI-2K ≥4) showed poor QoL compared with those with lower disease activity (SLEDAI-2K <4), with significant differences in the domains of physical health, planning, burden to others and fatigue (p = 0.001, p = 0.04, p = 0.03, p = 0.04, respectively). The confirmatory factor analysis using the eight domain loadings of the 34 items showed a poor fit (χ(2)/degree of freedom (df) 2.26, χ(2 )= 1128.6 (p < 0.001), root mean square error of approximation (RMSEA) = 0.167; goodness-of-fit index (GFI) = 0.606, comparative fit index (CFI) = 0.649)). Screeplot analysis suggested a five-factor loading structure and confirmatory factor analysis result of which is similar to the eight-factor model. A good internal consistency was observed (Cronbach's α 0.89-0.91). Test-retest reliability was good to excellent between baseline and day 15 (intraclass correlation coefficient (ICC) 0.90-0.98)., Conclusion: The Italian version of the LupusQoL(©) is a valid tool for adult patients with SLE., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

An excessive blood pressure (BP) reduction might be dangerous in high-risk patients with cardiovascular disease. In the Studio Italiano Sugli Effetti CARDIOvascolari del Controllo della Pressione Arteriosa SIStolica (Cardio-Sis), 1111 nondiabetic patients with systolic BP ≥150 mm Hg were randomly assigned to a systolic BP target <140 mm Hg (standard control) or <130 mm Hg (tight control). We stratified patients by absence (n=895) or presence (n=216) of established cardiovascular disease at entry. Antihypertensive treatment was open-label and tailored to each patient's needs. After 2-year follow-up, the primary end point of the study, electrocardiographic left ventricular hypertrophy, occurred less frequently in the tight than in the standard control group in the patients without (10.8% versus 15.2%) and with (14.1% versus 23.5%) established cardiovascular disease (P for interaction=0.82). The main secondary end point, a composite of cardiovascular events and all-cause death, occurred less frequently in the tight than in the standard control group both in patients without (1.47 versus 3.68 patient-years; P=0.016) and with (7.87 versus 11.22 patient-years; P=0.049) previous cardiovascular disease. In a multivariable Cox model, allocation to tight BP control reduced the risk of cardiovascular events to a similar extent in patients with or without overt cardiovascular disease at randomization (P for interaction=0.43). In conclusion, an intensive treatment aimed to lower systolic BP<130 mm Hg reduced left ventricular hypertrophy and improved clinical outcomes to a similar extent in patients with hypertension and without established cardiovascular disease.

Objective: The aim of the present study was to investigate the maternal and paternal specific contributions on the associations between family socioeconomic status, parental anthropometric factors, parental alliance, and family functioning. These were assessed separately for mothers and fathers, by means of a case-control study with families of Italian youths with and without overweight/obesity., Methods: Ninety families with children aged 11 to 16 years (mean = 13.27 years; SD = 1.5) participated in the study. Half of the families included children with overweight/obesity (n = 45). The body mass indices (BMIs) of youths and parents were measured and the former transformed in BMI z-scores. The parents completed the Parenting Alliance Measure and the Family Assessment Measure Version III, General Scale., Results: Higher levels of dysfunction in parental alliance and family functioning of the mothers and fathers of the overweight/obese group were found. Socioeconomic status did not contribute significantly to the prediction of overweight and obesity in youth. Both maternal and paternal BMIs were positively associated with youth overweight/obesity. The degrees of parental alliance perceived by both mothers (odds ratio [OR], 81; 95% confidence interval [CI], 0.72-0.90) and fathers (OR, 89; 95% CI, 0.81-0.98) predicted child's weight status. The perception of poor parental and familial functioning by both parents contributed to the prediction of overweight and obesity in youth (mother: OR, 1.06; 95% CI, 1.02-1.10; father: OR, 1.06; 95% CI, 1.01-1.11)., Conclusion: The results support a strong effect of parental and family functioning on a youth's overweight/obesity also from the father's perspective. The importance of considering the father's perspective is discussed.

Background: Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting., Methods: To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52 ± 16 years from Italy, U.S.A., Japan, and Australia, included in the 'ABP-International' registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine., Results: During a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24h HR (p=0.007 and =0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p=0.07 and =0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04-1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05-1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05-1.45) were excluded from analysis., Conclusions: At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Although repolarization abnormalities on ECG are frequent in post-menopausal hypertensive women, their prognostic value in these women is uncertain., Methods: We analyzed 908 hypertensive post-menopausal women consecutively included in the PIUMA (Progetto Ipertensione Umbria Monitoraggio Ambulatoriale) study. The median duration of follow-up was 8.6 years (range: 1-21). All women were untreated at entry. Drug treatment during follow-up was adjusted to single individuals. Standard 12-lead ECG was carried out at entry. The Minnesota Coding was used to define minor and major ("typical strain") repolarization abnormalities., Design: prospective observational study in essential hypertension., Results: Mean age at entry was 60 years. At baseline, ECG was normal in 707 women, minor ST-T changes were noted in 152 women, and a typical strain pattern was present in 49 subjects. Predictors of typical strain were age, diabetes and systolic blood pressure (BP). During follow-up there were 119 new cardiovascular (CV) events and 75 all-cause deaths. Typical strain was associated with a threefold higher risk of CV disease (HR: 3.16; 95% CI: 1.59-6.31; p=0.001) after adjustment for the significant influence of age, diabetes, serum creatinine, systolic BP and HDL-cholesterol. Women with minor LV repolarization abnormalities showed a non-significant excess risk of CV disease when compared with women with normal LV repolarization (HR: 1.25; 95% CI: 0.69-2.26; p=0.467). Similar results were obtained for all-cause mortality., Conclusions: Typical strain pattern, an easily detectable marker of altered LV repolarization, identifies post-menopausal hypertensive women at increased risk of CV disease and all-cause mortality., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown. We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients., Methods: In this randomised open-label trial undertaken in 44 centres in Italy, 1111 non-diabetic patients with systolic blood pressure 150 mm Hg or greater were randomly assigned to a target systolic blood pressure of less than 140 mm Hg (usual control; n=553) or less than 130 mm Hg (tight control; n=558). After stratification by centre, we used a computerised random function to allocate patients to either group. Observers who were unaware of randomisation read electrocardiograms and adjudicated events. Open-label agents were used to reach the randomised targets. The primary endpoint was the rate of electrocardiographic left ventricular hypertrophy 2 years after randomisation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00421863., Results: Over a median follow-up of 2.0 years (IQR 1.93-2.03), systolic and diastolic blood pressure were reduced by a mean of 23.5/8.9 mm Hg (SD 10.6/7.0) in the usual-control group and by 27.3/10.4 mm Hg (11.0/7.5) in the tight-control group (between-group difference 3.8 mm Hg systolic [95% CI 2.4-5.2], p<0.0001; and 1.5 mm Hg diastolic [0.6-2.4]; p=0.041). The primary endpoint occurred in 82 of 483 patients (17.0%) in the usual-control group and in 55 of 484 patients (11.4%) of the tight-control group (odds ratio 0.63; 95% CI 0.43-0.91; p=0.013). A composite cardiovascular endpoint occurred in 52 (9.4%) patients in the usual-control group and in 27 (4.8%) in the tight-control group (hazard ratio 0.50, 95% CI 0.31-0.79; p=0.003). Side-effects were rare and did not differ significantly between the two groups., Interpretation: Our findings lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension., Funding: Boehringer-Ingelheim, Sanofi-Aventis, Pfizer.

Objectives: Although the prognostic value of the day-night blood pressure (BP) changes is well established, the most appropriate method for definition of daytime and nighttime BP is still undefined. In a recent guidelines document of the European Society of Hypertension, there is no clear position in favor of one definition over other., Methods: In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulariale study, we analyzed the prognostic impact of the day-night BP changes by using three widely used different definitions of day and night (large fixed-clock intervals, narrow fixed-clock intervals, diary) in 2934 initially untreated participants with essential hypertension., Results: Three hundred and fifty-six cardiovascular events and 176 deaths over a median follow-up period of 7 years were observed. Nondippers showed a higher risk of total cardiovascular events and all-cause mortality than dippers regardless of the definition of day and night. Furthermore, the area under a receiver-operated characteristic curve analysis did not differ among the different definitions of day and night (large fixed-clock intervals, narrow fixed-clock intervals, diary) for total cardiovascular events and all-cause mortality (all P=NS)., Conclusion: The data suggest that the prognostic value of the diurnal BP changes is comparable when day and night are defined using large fixed-clock intervals, narrow fixed-clock intervals, or actual time spent in and out of bed.

Background: The independent prognostic value of daytime and night-time blood pressure (BP) variability estimated by noninvasive 24-h BP monitoring is unclear., Methods: We followed 2649 initially untreated subjects with essential hypertension for up to 16 years (mean, 6). Variability of BP was estimated by the standard deviation of daytime or night-time systolic BP (SBP) and diastolic BP (DBP). A BP variability either less than or equal to the group median or greater than the group median (12.7/10.4 mm Hg for daytime SBP/DBP and 10.8 and 8.9 mm Hg for night-time SBP/DBP) identified subjects at low or high BP variability., Results: During follow-up there were 167 new cardiac and 122 new cerebrovascular events. The rate of cardiac events (x100 person-years) was higher (all P < .05) in the subjects with high than in those with low BP variability (daytime SBP: 1.45 v 0.72, daytime DBP: 1.29 v 0.91; night-time SBP: 1.58 v 0.62; night-time DBP: 1.32 v 0.85). The rate of cerebrovascular events was also higher (all P < .05) in the subjects with high than in those with low BP variability. In a multivariate analysis, after adjustment for several confounders, a high night-time SBP variability was associated with a 51% (P = .024) excess risk of cardiac events. The relation of daytime BP variability to cardiac events and that of daytime and night-time BP variability to cerebrovascular events lost significance in the multivariate analysis., Conclusions: An enhanced variability in SBP during the night-time is an independent predictor of cardiac events in initially untreated hypertensive subjects.

A relation between left ventricular (LV) hypertrophy and depressed midwall systolic function has been described in hypertensive subjects. However, a strong confounding factor in this relation is concentric geometry, which is both a powerful determinant of depressed midwall systolic function and a correlate of LV mass in hypertension. To evaluate the independent contribution of LV mass to depressed systolic function, 1827 patients with never-treated essential hypertension (age 48 +/- 12 years, men 58%) underwent M-mode echocardiography under two-dimensional guidance. Relative wall thickness was the strongest determinant of low midwall fractional shortening (r = -0.63, P < 0.0001). The significant inverse relation observed between LV mass and midwall fractional shortening (r = -0.43, P < 0.0001) persisted after taking into account the effect of relative wall thickness (partial r = -0.27, P < 0.0001). Within each sex-specific quintile of relative wall thickness, prevalence of subnormal afterload-corrected midwall systolic function was greater in subjects with, than in subjects without, LV hypertrophy (P < 0.05 for the first, third, fourth and fifth quintile). In a multiple linear regression analysis, both LV mass (P < 0.0001) and relative wall thickness (P < 0.0001) were independent predictors of a reduced midwall fractional shortening. In conclusion, the inverse association between LV mass and midwall systolic function is partly independent from the effect of relative wall thickness. LV hypertrophy is a determinant of subclinical LV dysfunction independently of the concomitant changes in chamber geometry.

Background: It is uncertain whether left ventricular hypertrophy (LVH) confers an increased risk for cerebrovascular disease in apparently healthy patients with essential hypertension., Methods and Results: A total of 2363 initially untreated hypertensive patients (mean age 51+/-12 years, 47% women) free of previous cardiovascular disease were followed up for up to 14 years (mean 5 years). At entry, all patients underwent diagnostic tests, including ECG, echocardiography, and 24-hour ambulatory blood pressure (BP) monitoring. At entry, the prevalence of LVH was 17.6% by ECG (Perugia score) and 23.7% by echocardiography (LVM >125 g/m(2)). Over the subsequent years, 105 patients experienced a first stroke or transient ischemic attack. The cerebrovascular event rate was higher among patients with LVH at entry, diagnosed by either ECG or echocardiography, than among those without hypertrophy (both P<0.01). After control for the significant influence of age, sex, diabetes, and 24-hour mean ambulatory BP, LVH by ECG conferred an increased risk for cerebrovascular events (relative risk [RR] 1.79; 95% CI 1.17 to 2.76). LVH by echocardiography also conferred a higher risk for cerebrovascular events (RR 1.64; 95% CI 1.07 to 2.68). For each increase in LV mass of 1 SD (29 g/m(2)), there was a significant independent increase in the risk for cerebrovascular events (RR 1.31; 95% CI 1.09 to 1.58)., Conclusions: In apparently healthy patients with essential hypertension, LVH diagnosed by ECG or echocardiography confers an excess risk for stroke and transient ischemic attack independently of BP and other individual risk factors.