Myocardial oxygen supply and demand imbalance predicts mortality in older nursing home residents: The PARTAGE study.

BACKGROUND: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. METHODS: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. RESULTS: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. CONCLUSIONS: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. TRIAL REGISTRATION: NCT00901355, registered on ClinicalTrials.gov website.

Controlling nutritional status score predicts 2-year outcomes in elderly patients admitted for acute heart failure.

BACKGROUND: Heart failure (HF) is a major cause of death among the elderly. Its prevalence increases dramatically with age. The prevalence of malnourished subjects is high in hospitalized elderly patients. We aimed to investigate the prognostic role of malnutrition, assessed by controlling nutritional status (CONUT) score, on adverse clinical outcomes in the elderly admitted for acute HF. METHODS: We enrolled 293 patients (mean age 84 years; 48% men) consecutively admitted for acute HF to the Internal Medicine or Geriatrics Divisions at the 'IRCCS Sacro Cuore-Don Calabria' Hospital of Negrar (Verona, Italy) from 2013 to 2015. We predicted the risk of all-cause death, re-hospitalizations for HF and non-HF causes, and the composite of all-cause death or hospitalizations over 2-year follow-up. Patients were divided into four groups according to CONUT score: normal-CONUT (0-1; n = 30); mild-CONUT (2-3; n = 56); moderate-CONUT (4-7; n = 171); and severe-CONUT (≥ 8; n = 36). RESULTS: Higher CONUT scores were associated with older age and lower entry blood pressures. No difference in hemodynamics was noted at the discharge. Kaplan-Meier curves showed a significant association between worsening CONUT scores and risk of all-cause death (p < 0.01), re-hospitalizations (p < 0.01), or both (p < 0.001). Cox regression analysis revealed these significant associations persisted after adjustment for age, sex, pre-existing cardiovascular disease, diabetes, chronic kidney disease, heart rate, systolic blood pressure, and plasma brain natriuretic peptide levels at discharge (all-cause mortality HR = 1.29 (1.00-1.66), p = 0.049; hospitalization for HF HR = 1.36 (1.03-1.81), p = 0.033; hospitalization for non-HF HR = 1.38 (1.03-1.86), p = 0.034; composite outcome HR = 1.33 (1.07-1.64), p = 0.01). CONCLUSIONS: Malnutrition, assessed by the CONUT score, is common among elderly patients admitted for acute HF and is strongly related to increased long-term risk of all-cause death and re-hospitalizations.

Non-Invasive Assessment of Arterial Stiffness: Pulse Wave Velocity, Pulse Wave Analysis and Carotid Cross-Sectional Distensibility: Comparison between Methods.

Background: The stiffening of large elastic arteries is currently estimated in research and clinical practice by propagative and non-propagative models, as well as parameters derived from aortic pulse waveform analysis. Methods: Common carotid compliance and distensibility were measured by simultaneously recording the diameter and pressure changes during the cardiac cycle. The aortic and upper arm arterial distensibility was estimated by measuring carotid−femoral and carotid−radial pulse wave velocity (PWV), respectively. The augmentation index and blood pressure amplification were derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the common carotid artery. Results: 75 volunteers were enrolled in this study (50 females, average age 53.5 years). A significant inverse correlation was found between carotid distensibility and carotid−femoral PWV (r = −0.75; p < 0.001), augmentation index (r = −0.63; p < 0.001) and central pulse pressure (r = −0.59; p < 0.001). A strong correlation was found also between the total slope of the diameter/pressure rate carotid curves and aortic distensibility, quantified from the inverse of the square of carotid−femoral PWV (r = 0.67). No correlation was found between carotid distensibility and carotid−radial PWV. Conclusions: This study showed a close correlation between carotid−femoral PWV, evaluating aortic stiffness by using the propagative method, and local carotid cross-sectional distensibility.

Increased aortic stiffness in adults with chronic indeterminate Chagas disease.

An ever-increasing number of patients with chronic indeterminate Chagas disease are diagnosed with early vascular and cardiac abnormalities, as cardiovascular imaging becomes more sensitive. However, the currently available information on aortic stiffness (a prognostic marker for adverse cardiovascular outcomes) in these patients is scarce. In this study, we consecutively recruited 21 asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease and 14 Bolivian adults, who were seronegative for Trypanosoma cruzi infection. No participants had a prior history of heart disease, hypertension, diabetes, chronic kidney disease or atrial fibrillation. Carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), carotid intima-media thickness and conventional echocardiographic measurements were recorded in all participants. Patients with chronic indeterminate Chagas disease had significantly higher cf-PWV (7.9±1.3 vs. 6.4±1.1 m/s, p = 0.003) and greater HOMA-estimated insulin resistance than subjects without Chagas disease. The two groups did not significantly differ in terms of age, sex, smoking, adiposity measures, blood pressure, plasma lipids, fasting glucose levels as well as cr-PWV, carotid intima-media thickness measurements, left ventricular mass and function. Presence of chronic indeterminate Chagas disease was significantly associated with increasing cf-PWV values (ß coefficient: 1.31, 95% coefficient interval 0.44 to 2.18, p = 0.005), even after adjustment for age, sex, heart rate, systolic blood pressure and insulin resistance. In conclusion, asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease have an early and marked increase in aortic stiffness, as measured by cf-PWV, when compared to Bolivian adults who were seronegative for Trypanosoma cruzi infection.

Interest of Combined Blood Pressure Measurements in Very Old Frail Subjects: The PARTAGE Study.

BACKGROUND: Several clinical studies have shown that blood pressure (BP) measurements in very old frail individuals are of limited interest due to the fact that several age-related alterations and geriatric syndromes may modify BP. We studied in persons over 80-year old living in nursing homes the combined effects of 3 BP patterns on total mortality and major cardiovascular (CV) events: (i) low pulse pressure amplification (L-PPA) between carotid and brachial artery, (ii) systolic BP (SBP) <130 mm Hg (L-SBP), under >1 antihypertensive drugs, and (iii) changes in SBP between supine and upright position of >20 mm Hg in both directions (hypotension/hypertension, orthostatic SBP [O-SBP]). METHODS: This analysis was performed in subjects of the PARTAGE study presenting all these 3 measurements (n = 883). The combined effects of L-PPA, L-SBP, and O-SBP were studied during the 2 years followed-up period. RESULTS: After adjusting for age, sex, and history of CV events, all 3 BP patterns were independent determinants of major CV events (L-PPA, (P = 0.023); L-SBP, (P = 0.050); O-SBP, (P = 0.015)), whereas L-PPA (P = 0.012) and L-SBP (P = 0.006) were also independent determinants of total mortality. Compared with the subjects without any BP pattern, the presence of 2 or 3 BP patterns was associated with an increase in total mortality and major CV events greater than 2 and 2.5 times, respectively. CONCLUSIONS: In very old frail subjects, there is a particular interest for using different BP measurement approaches, than in younger populations, in order to evaluate the risks related to the BP levels. CLINICAL TRIALS REGISTRATION: Trial Number: NCT00901355 (Clinical Trials.gov).

Non-alcoholic fatty liver disease and increased risk of all-cause mortality in elderly patients admitted for acute heart failure.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for incident heart failure (HF). It is currently unknown whether NAFLD predicts all-cause mortality in patients admitted for acute HF. We aimed to assess whether NAFLD and its severity (diagnosed by ultrasonography and non-invasive fibrosis biomarkers) were associated with increased all-cause mortality in this particularly high-risk patient population. METHODS: We studied 264 elderly patients, who were consecutively admitted for acute HF to the hospital between years 2013 and 2015, after excluding those with acute myocardial infarction, severe valvular heart diseases, kidney failure, cancer, cirrhosis of any etiology or known chronic liver diseases. Follow-up of patients continued until November 1, 2017. RESULTS: Over a mean follow-up of 23.2 months (range: 1 day-58 months), there were 140 (53%) total deaths. Of these, 24 deaths occurred during the first hospital admission (in-hospital death) and 116 deaths occurred after the hospital discharge during the follow-up period. Patients with NAFLD at hospital admission had significantly higher cumulative incidence rates of in-hospital and post-discharge all-cause mortality (singly or in combination) compared with those without NAFLD. This mortality risk was particularly high among patients with advanced NAFLD fibrosis. In Cox regression analysis, NAFLD was associated with an increased risk of all-cause mortality (adjusted-hazard ratio 1.82, 95% confidence intervals 1.22-2.81, p < 0.005) even after adjustment for established risk factors and potential confounding variables. CONCLUSIONS: NAFLD and its severity were independently associated with increased risk of in-hospital and post-discharge all-cause mortality in elderly patients admitted for acute HF.

Nonalcoholic fatty liver disease and increased risk of 1-year all-cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure.

Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for heart failure (HF). Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission) was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona) over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, end-stage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR) for the associations between NAFLD and the outcome(s) of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes). Patients with NAFLD (n = 109; 51.4%) had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78-9.10, p<0.0001) after adjustment for established risk factors and potential confounders. Similar results were found for 1-year cardiac re-hospitalization (adjusted-hazard ratio 8.05, 95% confidence intervals 3.77-15.8, p<0.0001). In conclusion, NAFLD and its severity were strongly and independently associated with an increased risk of 1-year all-cause and cardiac re-hospitalization in elderly patients admitted with acute HF.

Early impairment in left ventricular longitudinal systolic function is associated with an increased risk of incident atrial fibrillation in patients with type 2 diabetes.

AIMS: It is known that type 2 diabetic patients are at high risk of atrial fibrillation (AF). However, the early echocardiographic determinants of AF vulnerability in this patient population remain poorly known. METHODS: We followed-up for 2years a sample of 180 consecutive outpatients with type 2 diabetes, who were free from AF and ischemic heart disease at baseline. All patients underwent a baseline echocardiographic-Doppler evaluation with tissue Doppler and 2-D strain analysis. Standard electrocardiograms were performed twice per year, and a diagnosis of incident AF was confirmed in affected patients by a single cardiologist. RESULTS: Over the 2-year follow-up period, 14 (7.8%) patients developed incident AF. In univariate analyses, echocardiographic predictors of new-onset AF were greater indexed cardiac mass, larger indexed left atrial volume (LAVI), lower global longitudinal strain (LSSYS), lower global diastolic strain rate during early phase of diastole (SRE), lower global diastolic strain rate during late phase of diastole (SRL), and higher E/SRE ratio. Multivariate logistic regression analysis showed that lower LSSYS remained the only significant predictor of new-onset AF (adjusted-odds ratio 1.63, 95%CI 1.17-2.27; p<0.005) after adjustment for age, sex, diabetes duration, indexed cardiac mass and LAVI. Results were unchanged even after adjustment for body mass index, hypertension and glycemic control. CONCLUSIONS: This is the first prospective study to show that early LSSYS impairment independently predicts the risk of new-onset AF in type 2 diabetic patients with preserved ejection fraction and without ischemic heart disease. Future larger prospective studies are needed to confirm these findings.

Nonalcoholic Fatty Liver Disease Is Associated With Ventricular Arrhythmias in Patients With Type 2 Diabetes Referred for Clinically Indicated 24-Hour Holter Monitoring.

OBJECTIVE: Recent studies have suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of heart rate-corrected QT interval prolongation and atrial fibrillation in patients with type 2 diabetes. Currently, no data exist regarding the relationship between NAFLD and ventricular arrhythmias in this patient population. RESEARCH DESIGN AND METHODS: We retrospectively analyzed the data of 330 outpatients with type 2 diabetes without preexisting atrial fibrillation, end-stage renal disease, or known liver diseases who had undergone 24-h Holter monitoring for clinical reasons between 2013 and 2015. Ventricular arrhythmias were defined as the presence of nonsustained ventricular tachycardia (VT), >30 premature ventricular complexes (PVCs) per hour, or both. NAFLD was diagnosed by ultrasonography. RESULTS: Compared with patients without NAFLD, those with NAFLD (n = 238, 72%) had a significantly higher prevalence of >30 PVCs/h (19.3% vs. 6.5%, P < 0.005), nonsustained VT (14.7% vs. 4.3%, P < 0.005), or both (27.3% vs. 9.8%, P < 0.001). NAFLD was associated with a 3.5-fold increased risk of ventricular arrhythmias (unadjusted odds ratio [OR] 3.47 [95% CI 1.65-7.30], P < 0.001). This association remained significant even after adjusting for age, sex, BMI, smoking, hypertension, ischemic heart disease, valvular heart disease, chronic kidney disease, chronic obstructive pulmonary disease, serum γ-glutamyltransferase levels, medication use, and left ventricular ejection fraction (adjusted OR 3.01 [95% CI 1.26-7.17], P = 0.013). CONCLUSIONS: This is the first observational study to show that NAFLD is independently associated with an increased risk of prevalent ventricular arrhythmias in patients with type 2 diabetes.

Nonalcoholic Fatty Liver Disease Is Associated With Higher 1-year All-Cause Rehospitalization Rates in Patients Admitted for Acute Heart Failure.

Repeat hospitalization due to acute heart failure (HF) is a global public health problem that markedly impacts on health resource use. Identifying novel predictors of rehospitalization would help physicians to determine the optimal postdischarge plan for preventing HF rehospitalization. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for many heart diseases, including HF. We assessed whether NAFLD at hospital admission predicts 1-year all-cause rehospitalization in patients with acute HF. We enrolled all patients consecutively admitted for acute HF to our General Medicine Division, from January 2013 to April 2014, after excluding patients with acute myocardial infarction, severe heart valve diseases, malignancy, known liver diseases, and those with volume overload related to extracardiac causes. NAFLD was diagnosed by ultrasonography and exclusion of competing etiologies. The primary outcome of the study was the 1-year all-cause rehospitalization rate. Among the 107 patients enrolled in the study, the cumulative rehospitalization rate was 12.1% at 1 month, 25.2% at 3 months, 29.9% at 6 months, and 38.3% at 1 year. Patients with NAFLD had markedly higher 1-year rehospitalization rates than those without NAFLD (58% vs 21% at 1 y; P < 0.001 by the log-rank test). Cox regression analysis revealed that NAFLD was associated with a 5.5-fold increased risk of rehospitalization (adjusted hazard ratio 5.56, 95% confidence interval 2.46-12.1, P < 0.001) after adjustment for multiple HF risk factors and potential confounders. In conclusion, NAFLD was independently associated with higher 1-year rehospitalization in patients hospitalized for acute HF.

Evidence for a Prognostic Role of Orthostatic Hypertension on Survival in a Very Old Institutionalized Population.

UNLABELLED: In old individuals, regulation of blood pressure during postural changes is impaired. Several studies have assessed the clinical impact of orthostatic hypotension (OHypoT) during the aging process. By contrast, the prevalence and prognostic role of the increase in blood pressure in upright position (orthostatic hypertension, OHyperT) in old adults remain unknown. We investigated the association of OHyperT with cardiovascular morbidity and mortality in a population of old institutionalized subjects. A 2-year follow-up longitudinal study was conducted on 972 subjects (mean age [SD] 88 [5]) from the PARTAGE (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population) study, able to maintain a standing position. OHyperT was defined as an increase in systolic blood pressure ≥20 mm Hg during the first and third minute of standing. Three groups of subjects were compared: orthostatic normotension (n=540), OHypoT (n=157), and OHyperT (n=275). OHyperT prevalence (28%) was higher than OHypoT (16%). Sitting systolic blood pressure was higher in OHypoT compared with orthostatic normotension and OHyperT groups (146 [23] versus 136 [21] and 136 [20] mm Hg, respectively, P<0.001). The OHyperT group was associated with a greater risk of cardiovascular morbidity and mortality than orthostatic normotension (hazard ratio 1.51 [1.09-2.08], P<0.01) and remained unchanged after adjustment for age, sex, sitting systolic blood pressure, and comorbidities. No difference in cardiovascular morbidity and mortality was observed between OHyperT and OHypoT groups. In conclusion, in a old frail population, the increase in systolic blood pressure during upright position occurs frequently and is associated with higher cardiovascular morbidity and mortality independently of sitting blood pressure levels and major comorbidities. Health professional should take into account not only the decrease but also the increase in blood pressure when standing up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00901355.

Nonalcoholic Fatty Liver Disease Is Independently Associated with Early Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes.

Accumulating evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with left ventricular diastolic dysfunction (LVDD) in nondiabetic individuals. To date, there are very limited data on this topic in patients with type 2 diabetes and it remains uncertain whether NAFLD is independently associated with the presence of LVDD in this patient population. We performed a liver ultrasonography and trans-thoracic echocardiography (with speckle-tracking strain analysis) in 222 (156 men and 66 women) consecutive type 2 diabetic outpatients with no previous history of ischemic heart disease, chronic heart failure, valvular diseases and known hepatic diseases. Binary logistic regression analysis was used to examine the association between NAFLD and the presence/severity of LVDD graded according to the current criteria of the American Society of Echocardiography, and to identify the variables that were independently associated with LVDD, which was included as the dependent variable. Patients with ultrasound-diagnosed NAFLD (n = 158; 71.2% of total) were more likely to be female, overweight/obese, and had longer diabetes duration, higher hemoglobin A1c and lower estimated glomerular filtration rate (eGFR) than those without NAFLD. Notably, they also had a remarkably greater prevalence of mild and/or moderate LVDD compared with those without NAFLD (71% vs. 33%; P<0.001). Age, hypertension, smoking, medication use, E/A ratio, LV volumes and mass were comparable between the two groups of patients. NAFLD was associated with a three-fold increased odds of mild and/or moderate LVDD after adjusting for age, sex, body mass index, hypertension, diabetes duration, hemoglobin A1c, eGFR, LV mass index and ejection fraction (adjusted-odds ratio 3.08, 95%CI 1.5-6.4, P = 0.003). In conclusion, NAFLD is independently associated with early LVDD in type 2 diabetic patients with preserved systolic function.

Heart valve calcification in patients with type 2 diabetes and nonalcoholic fatty liver disease.

PURPOSE: Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are two powerful predictors of adverse cardiovascular outcomes in patients with type 2 diabetes, but the etiology of valvular calcification is uncertain. Nonalcoholic fatty liver disease (NAFLD) is an emerging cardiovascular risk factor and is very common in type 2 diabetes, but whether NAFLD is associated with valvular calcification in this group of patients is presently unknown. METHODS: We undertook a cross-sectional study of 247 consecutive type 2 diabetic outpatients with no previous history of heart failure, valvular heart diseases (aortic stenosis, mitral stenosis, moderate or severe aortic and mitral regurgitation) or hepatic diseases. Presence of MAC and AVS was detected by echocardiography. NAFLD was diagnosed by ultrasonography. RESULTS: Overall, 139 (56.3%) patients had no heart valve calcification (HVC-0), 65 (26.3%) patients had one valve affected (HVC-1) and 43 (17.4%) patients had both valves affected (HVC-2). 175 (70.8%) patients had NAFLD and the prevalence of this disease markedly increased in patients with HVC-2 compared with either HVC-1 or HVC-0 (86.1% vs. 83.1% vs. 60.4%, respectively; p < 0.001). NAFLD was significantly associated with AVS and/or MAC (unadjusted-odds ratio 3.51, 95% CI 1.89-6.51, p < 0.001). Adjustments for age, sex, waist circumference, smoking, blood pressure, hemoglobin A1c, LDL-cholesterol, kidney function parameters, medication use and echocardiographic variables did not appreciably weaken this association (adjusted-odds ratio 2.70, 95% CI 1.23-7.38, p < 0.01). CONCLUSIONS: Our results show that NAFLD is an independent predictor of cardiac calcification in both the aortic and mitral valves in patients with type 2 diabetes.

Treatment With Multiple Blood Pressure Medications, Achieved Blood Pressure, and Mortality in Older Nursing Home Residents: The PARTAGE Study.

IMPORTANCE: Clinical evidence supports the beneficial effects of lowering blood pressure (BP) levels in community-living, robust, hypertensive individuals older than 80 years. However, observational studies in frail elderly patients have shown no or even an inverse relationship between BP and morbidity and mortality. OBJECTIVE: To assess all-cause mortality in institutionalized individuals older than 80 years according to systolic BP (SBP) levels and number of antihypertensive drugs. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study included elderly residents of nursing homes. The interaction between low (<130 mm Hg) SBP and the presence of combination antihypertensive treatment on 2-year all-cause mortality was analyzed. A total of 1127 women and men older than 80 years (mean, 87.6 years; 78.1% women) living in nursing homes in France and Italy were recruited, examined, and monitored for 2 years. Blood pressure was measured with assisted self-measurements in the nursing home during 3 consecutive days (mean, 18 measurements). Patients with an SBP less than 130 mm Hg who were receiving combination antihypertensive treatment were compared with all other participants. MAIN OUTCOMES AND MEASURES: All-cause mortality over a 2-year follow-up period. RESULTS: A significant interaction was found between low SBP and treatment with 2 or more BP-lowering agents, resulting in a higher risk of mortality (unadjusted hazard ratio [HR], 1.81; 95% CI, 1.36-2.41); adjusted HR, 1.78; 95% CI, 1.34-2.37; both P < .001) in patients with low SBP who were receiving multiple BP medicines compared with the other participants. Three sensitivity analyses confirmed the significant excess of risk: propensity score-matched subsets (unadjusted HR, 1.97; 95% CI, 1.32-2.93; P < .001; adjusted HR, 2.05; 95% CI, 1.37-3.06; P < .001), adjustment for cardiovascular comorbidities (HR, 1.73; 95% CI, 1.29-2.32; P < .001), and exclusion of patients without a history of hypertension who were receiving BP-lowering agents (unadjusted HR, 1.82; 95% CI, 1.33-2.48; P < .001; adjusted HR, 1.76; 95% CI, 1.28-2.41; P < .001). CONCLUSIONS AND RELEVANCE: The findings of this study raise a cautionary note regarding the safety of using combination antihypertensive therapy in frail elderly patients with low SBP (<130 mm Hg). Dedicated, controlled interventional studies are warranted to assess the corresponding benefit to risk ratio in this growing population.

Association of nonalcoholic fatty liver disease with QTc interval in patients with type 2 diabetes.

BACKGROUND AND AIMS: The relationship between nonalcoholic fatty liver disease (NAFLD) and prolonged heart rate-corrected QT (QTc) interval, a risk factor for ventricular arrhythmias and sudden cardiac death, is currently unknown. We therefore examined the relationship between NAFLD and QTc interval in patients with type 2 diabetes. METHODS AND RESULTS: We studied a random sample of 400 outpatients with type 2 diabetes. Computerized electrocardiograms were performed for analysis and quantification of QTc interval. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis in the absence of other liver diseases. Mean QTc interval and the proportion of those with increased QTc interval (defined as either QTc interval above the median, i.e. ≥416 ms, or QTc interval >440 ms) increased steadily with the presence and ultrasonographic severity of NAFLD. NAFLD was associated with increased QTc interval (odds ratio [OR] 2.16, 95% CI 1.4-3.4, p < 0.001). Adjustments for age, sex, smoking, alcohol consumption, BMI, hypertension, electrocardiographic left ventricular hypertrophy, diabetes-related variables and comorbid conditions did not attenuate the association between NAFLD and increased QTc interval (adjusted-OR 2.26, 95% CI 1.4-3.7, p < 0.001). Of note, the exclusion of those with established coronary heart disease or peripheral artery disease from analysis did not appreciably weaken this association. CONCLUSION: This is the first study to demonstrate that the presence and severity of NAFLD on ultrasound is strongly associated with increased QTc interval in patients with type 2 diabetes even after adjusting for multiple established risk factors and potential confounders.

Nonalcoholic fatty liver disease is associated with aortic valve sclerosis in patients with type 2 diabetes mellitus.

BACKGROUND: Recent epidemiological data suggest that non-alcoholic fatty liver disease (NAFLD) is closely associated with aortic valve sclerosis (AVS), an emerging risk factor for adverse cardiovascular outcomes, in nondiabetic and type 2 diabetic individuals. To date, nobody has investigated the association between NAFLD and AVS in people with type 2 diabetes, a group of individuals in which the prevalence of these two diseases is high. METHODS AND RESULTS: We recruited 180 consecutive type 2 diabetic patients without ischemic heart disease, valvular heart disease, hepatic diseases or excessive alcohol consumption. NAFLD was diagnosed by liver ultrasonography whereas AVS was determined by conventional echocardiography in all participants. In the whole sample, 120 (66.7%) patients had NAFLD and 53 (29.4%) had AVS. No patients had aortic stenosis. NAFLD was strongly associated with an increased risk of prevalent AVS (odds ratio [OR] 2.79, 95% CI 1.3-6.1, p<0.01). Adjustments for age, sex, duration of diabetes, diabetes treatment, body mass index, smoking, alcohol consumption, hypertension, dyslipidemia, hemoglobin A1c and estimated glomerular filtration rate did not attenuate the strong association between NAFLD and risk of prevalent AVS (adjusted-OR 3.04, 95% CI 1.3-7.3, p = 0.01). CONCLUSIONS: Our results provide the first demonstration of a positive and independent association between NAFLD and AVS in patients with type 2 diabetes mellitus.

Relation of elevated serum uric acid levels to incidence of atrial fibrillation in patients with type 2 diabetes mellitus.

The association between serum uric acid (SUA) levels and atrial fibrillation (AF) is currently poorly known. We examined the association between SUA levels and risk of incident AF in patients with type 2 diabetes mellitus. We followed for 10 years a random sample of 400 type 2 diabetic outpatients, who were free from AF at baseline. A standard 12-lead electrocardiography was undertaken annually and a diagnosis of incident AF was confirmed in affected participants by a single cardiologist. Over 10 years, there were 42 incident AF cases (cumulative incidence of 10.5%). Elevated SUA level was associated with an increased risk of incident AF (odds ratio 2.43, 95% confidence interval 1.8 to 3.4, p <0.0001 for each 1-SD increase in SUA level). Adjustments for age, gender, body mass index, hypertension, chronic kidney disease, electrocardiographic features (left ventricular hypertrophy and PR interval), and use of diuretics and allopurinol did not attenuate the association between SUA and incident AF (adjusted odds ratio 2.44, 95% confidence interval 1.6 to 3.9, p <0.0001). Further adjustment for variables that were included in the 10-year Framingham Heart Study-derived AF risk score did not appreciably weaken this association. Results remained unchanged even when SUA was modeled as a categorical variable (stratifying by either SUA median or hyperuricemia), and when patients with previous coronary heart disease or heart failure were excluded from analysis. In conclusion, our findings suggest that elevated SUA levels are strongly associated with an increased incidence of AF in patients with type 2 diabetes mellitus even after adjustment for multiple clinical risk factors for AF.