Filippo Valbusa

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.

Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study.

Objective Orthostatic hypotension has a prognostic role in determining cardiovascular and all-cause mortality. The aim of this study was to assess the prevalence of orthostatic hypotension and its association with blood pressure (BP) levels, arterial stiffness, cardiovascular and metabolic disorders and medication in individuals aged 80 years and over living in nursing home. Methods In 994 individuals (77% women, mean age 88±5 years), the presence of orthostatic hypotension was tested according to American Autonomic Society and American Academy of Neurology guidelines. Arterial stiffness was evaluated with carotid–femoral pulse wave velocity (cf-PWV), peripheral to central pulse pressure amplification (PPA) and augmentation index. Cardiovascular and metabolic disorders as well as medications were recorded from patients’ medical records. Results The prevalence of orthostatic hypotension was 18%. Treated hypertensive patients with SBP 140 mmHg or less had a lower prevalence of orthostatic hypotension than patients with SBP more than 140 mmHg (respectively, 13 vs. 23%; P < 0.001). Individuals with orthostatic hypotension exhibited higher brachial and central PP than individuals without orthostatic hypotension (respectively, 69±18 vs. 65±16 mmHg and 57±17 vs. 54±15 mmHg; P < 0.01). In these same individuals, a significant increase in augmentation index (31.1±14.0 vs. 27.2±13.6%; P < 0.01), but not in cf-PWV or in PPA, was observed. Individuals with orthostatic hypotension were treated more frequently with &bgr;-blockers and less frequently with angiotensin receptor blockers or nitrates than individuals without orthostatic hypotension (P < 0.05 for both). Conclusion Contrary to the general belief, elderly individuals with well controlled BP (SBP < 140 mmHg) show lower orthostatic hypotension, thus constituting a complementary argument for efficaciously treating hypertension in these individuals.

Blood pressure and pulse wave velocity values in the institutionalized elderly aged 80 and over: baseline of the PARTAGE study.

Objective The aim of the longitudinal study PARTAGE (predictive values of blood pressure and arterial stiffness in institutionalized very aged population) was to determine the predictive value of blood pressure (BP) and arterial stiffness for overall mortality, major cardiovascular events and cognitive decline in a large population of institutionalized patients aged 80 and over. In the study herein, we present the baseline data values of this study. Methods A total of 1130 patients were recruited (878 women), living in French and Italian nursing homes. Clinical and 3-day self-measurements of BP were conducted. Aortic and upper limb pulse wave velocity were obtained using a PulsePen tonometer. Results Of this population, 76% of women and 60% of men had a known hypertension and over 91% of the patients were under antihypertensive treatment; 51% of the treated hypertensive patients were well controlled (systolic BP <140 mmHg). No significant differences were found between clinical and self-measured BP. With age, there was an increase in pulse pressure (P < 0.001) due to a decrease in diastolic BP (P < 0.001), without any increase in systolic BP. Aortic but not peripheral pulse wave velocity significantly increased with age (P < 0.005). Conclusion Baseline values obtained herein demonstrate that elderly patients living in nursing homes present hemodynamic characteristics which are different to those described in community-living elderly populations, and indicate the interest of assessing, in longitudinal studies, the role of BP and arterial stiffness in morbidity and mortality in this population.

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.

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.

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.

Increased Aortic Pulse Wave Velocity as Measured by Echocardiography Is Strongly Associated with Poor Prognosis in Patients with Heart Failure

BACKGROUND An increased aortic pulse wave velocity (PWV), a marker of arterial stiffness, is associated with poor prognosis in various diseases. In patients with heart failure (HF), an increased aortic PWV is associated with low peak exercise oxygen consumption, which is a strong risk factor of adverse clinical outcomes. However, it remains unknown if an increased aortic PWV predicts poor prognosis in patients with HF, independent of peak exercise oxygen consumption. METHODS AND RESULTS We enrolled 156 patients with HF and left ventricular ejection fraction <45%, who were followed up for a mean (SD) period of 36 ± 19 months. At baseline, all the patients underwent a complete echocardiography with aortic PWV as measured by Doppler ultrasonography and peak exercise oxygen consumption as measured by bicycle exercise testing with expiratory gas exchange monitoring. During the follow-up period, 20 patients (12.8%) died and 15 patients (9.6%) were hospitalized for worsening HF. In the Kaplan-Meier analysis, patients in the first tertile of aortic PWV had a lower risk of developing cardiac death or hospitalization (combined end point) than those in the second and third tertile combined (P < .001). In Cox regression analysis, increased aortic PWV (both as a continuous and categorical variable) was significantly associated with an increased risk of adverse clinical outcomes after adjustment for peak exercise oxygen consumption and other clinical risk factors (P < .05). CONCLUSIONS Increased aortic PWV, as measured by echocardiography, independently predicted adverse clinical outcomes (cardiac death or hospitalization) among patients with HF.

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

Abstract—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 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.