Comparison of different frailty instruments for prediction of functional decline in older hypertensive outpatients (HYPER-FRAIL pilot study 2).

BACKGROUND AND AIMS: Few studies have evaluated frailty in older hypertensive individuals and the most appropriate tools to identify frailty in this population have yet to be identified. This study compared the performance of six frailty instruments in the prediction of 1-year functional decline in older hypertensive outpatients. METHODS: The HYPERtension and FRAILty in Older Adults (HYPER-FRAIL) longitudinal pilot study involved hypertensive participants ≥75 years from two geriatric outpatient clinics at Careggi Hospital, Florence, Italy, undergoing identification of frailty with four frailty scales (Fried Frailty Phenotype, Frailty Index [FI], Clinical Frailty Scale [CFS], Frailty Postal Score) and two physical performance tests (Short Physical Performance Battery [SPPB] and gait speed). Prediction of 1-year functional decline (i.e. a ≥ 10-point Barthel Index decrease between baseline and follow-up) was examined based on ROC curve analysis and multivariable logistic regression. RESULTS: Among 116 participants, 24 % reported functional decline. In the ROC curve analyses, FI (AUC=0.76), CFS (AUC=0.77), gait speed (AUC=0.73) and the SPPB (AUC=0.77) achieved the best predictive performance, with FI ≥0.21 and CFS ≥4 showing the highest sensitivity (82 %) and negative predictive value (91 %). Frailty identified with FI, CFS or physical performance tests was associated with an increased risk of 1-year functional decline, independently of baseline functional status and comorbidity burden. CONCLUSIONS: FI, CFS and physical performance tests showed similar predictive ability for functional decline in hypertensive outpatients. The CFS and gait speed might be more suitable for clinical use and may be useful to identify non-frail individuals at lower risk of functional decline.

Targets for deprescribing in patients with hypertension and reflex syncope.

BACKGROUND: We aimed to identify the target of deprescribing, i.e. the 24-hour SBP increase needed to achieve the greatest reduction of SBP drops. METHOD: Forty hypertensive patients (mean age 73.6 ± 9.3 years, 26 females) with reflex syncope and SBP drops on a screening ABPM were advised to withdraw or to reduce their therapy. The study objective was the reduction of SBP drops <90 mmHg and <100 mmHg on a second ABPM performed within 3 months. RESULTS: Out of a total of 98 drugs taken during ABPM 1, 44 were withdrawn, 16 had a dose reduction and 38 remained unchanged at the time of ABPM 2. 24-hour SBP increased from 119.7 ± 10.1 mmHg to 129.4 ± 13.2 mmHg during ABPM2. Total disappearance of daytime SBP drops <100 mmHg was achieved in 20 (50 %) patients who had 24-hour SBP of 134±13 mmHg and an increase from ABPM 1 of 12 (IQR 5-20) mmHg. Compared with the 20 patients who had persistence of drops, these patients had a greater reduction of the number of hypotensive drugs (67 % versus 19 %, p = 0.002) and a greater rate of withdrawals (62 % versus 29 %, p = 0.003). CONCLUSION: In hypertensive patients with reflex syncope, an increase of 12 mmHg and an absolute value of 24-hour SBP of 134 mmHg appear to represent the optimal goals aimed to prevent SBP drops. Drugs withdrawal, rather than simply dose reduction, is mostly required to achieve the above target.

Determinants of health status in older patients with transthyretin cardiac amyloidosis: a prospective cohort study.

BACKGROUND: Whether, and to what extent, frailty and other geriatric domains are linked to health status in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown. AIMS: To determine the association of frailty with health status [defined by the Kansas City Cardiomyopathy Questionnaire (KCCQ)] in patients with ATTR-CA. METHODS: Consecutive ATTR-CA patients undergoing cardiovascular assessment at a tertiary care clinic from September 2021 to September 2023 were invited to participate. KCCQ, frailty and social environment were recorded. Frailty was assessed using the modified Frailty Index (mFI), mapping 11 variables from the Canadian Study of Health and Aging (frailty ≥0.36). RESULTS: Of 168 screened ATTR-CA patients, 138 [83% men, median age of 79 (75-84) years] were enrolled in the study. Median KCCQ was 66 (50-75). wtATTR-CA was the most prevalent form (N = 113, 81.9%). The most frequent cardiac variant was Ile68Leu (17/25 individuals with vATTR-CA). Twenty (14.5%) patients were considered frail, and prevalence of overt disability was 6.5%. At multivariable linear regression analysis, factors associated with worsening KCCQ were age at evaluation, the mFI, NYHA Class, and NAC Score. Gender, ATTR-CA type, phenotype, and LVEF were not associated with health status. DISCUSSION: In older patients diagnosed with ATTR-CA, frailty, symptoms, and disease severity were associated with KCCQ. CONCLUSIONS: Functional status is a determinant of quality of life and health status in older individuals with a main diagnosis of ATTR-CA. Future research may provide more in-depth knowledge on the association of frailty in patients with ATTR-CA with respect to quality of life and prognosis.

Incidence and risk factors for non-cardiac syncope in a cohort of patients addressing an accredited Arterial Hypertension Center: the Innocent Study.

BACKGROUND: Hypotensive susceptibility in hypertensive patients could facilitate orthostatic hypotension, syncope and fall. The aim of this study was to identify incidence, clinical form, complications and risk factors for non-cardiac syncope in a cohort of hypertensive patients. METHODS: This is an observational, case-controlled, retrospective study carried out on 168 patients, evaluated at the Hypertension Center of the University Hospital of Parma (Italy). Based on the presence of episodes of syncope during the six months prior to enrolment, we identified cases and controls and then we compared them to personal data, comorbidities, current drug regimens, presence of orthostatic hypotension, office and ambulatory blood pressure monitoring (ABPM) blood pressure (BP) values. RESULTS: In patients with previous syncopal episodes (29.8% of total), we more frequently found female gender, comorbidities associated with autonomic dysfunction, diuretics and non-CV drugs potentially associated with hypotension in their current drug regimen, orthostatic hypotension and lower office and ABPM BP values. CONCLUSIONS: To identify hypertensive patients at higher risk for syncope and falls, physicians should focus on comorbidities and current drug regimens, systematically perform an active standing test to identify orthostatic hypotension, employ ABPM to compare BP values with the pre-established target and highlight systolic BP drops and abnormalities suggesting concomitant autonomic dysfunction. The modulation of antihypertensive therapy is an effective tool to counteract the risk of non-cardiac syncope, with possible trauma or other negative influences.

Tolerability of Antihypertensive Medications: The Influence of Age.

INTRODUCTION: Despite high prevalence of hypertension, few studies have analysed the adverse effects (AEs) of antihypertensive medications, especially in older patients. AIM: To investigate the prevalence and associated factors of antihypertensive-related AEs, focusing on the influence of age on treatment tolerability. METHODS: We retrospectively investigated antihypertensive-related AEs in patients evaluated at the Hypertension Clinic of Careggi Hospital, Florence, Italy, between January 2017 and July 2020. Multivariable regression models were generated to analyse variables associated with AEs in the overall sample and in participants ≥75 years. RESULTS: Among 622 subjects (mean age 64.8 years, 51.4% female), the most frequently reported AEs were calcium-channel blockers (CCB)-related ankle swelling (26.8%) and ACEi-induced cough (15.1%). Ankle swelling was more common in older patients (35.7% vs 22.3%, p = 0.001; odds ratio [OR] 1.94, 95%CI 1.289-2.912) and was independently associated with Body Mass Index (BMI, adjOR 1.073) and angiotensin-receptor antagonists (adjOR 1.864). The association with BMI was confirmed in older patients (adjOR 1.134). ACEi-induced cough showed similar prevalence in younger and older patients (13.9% vs 15.6%, p = 0.634), being independently associated with female sex (adjOR 2.118), gastroesophageal reflux disease (GERD, adjOR 2.488) and SNRI therapy (adjOR 8.114). The association with GERD was confirmed in older patients (adjOR 3.238). CONCLUSIONS: CCB-related ankle swelling and ACEi-induced cough represent the most common antihypertensive-related AEs, also at old age. Older patients showed a two-fold increased risk of ankle swelling, that was also independently associated with BMI. ACEi-induced cough had similar prevalence at younger and old ages, being independently associated with GERD.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

PURPOSE: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. METHODS: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. RESULTS: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors. CONCLUSIONS: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.

Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

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.

Sarcopenia increases mortality risk in liver transplantation: a systematic review and meta-analysis.

INTRODUCTION: Liver transplantation is an efficacious treatment option for those with liver cirrhosis. However, the prognostic role of sarcopenia in these patients is unknown. Given this background, we conducted a systematic review and meta-analysis of the impact of sarcopenia on mortality in patients listed, evaluated and undergoing liver transplantation. EVIDENCE ACQUISITION: Several databases were searched from the inception to December 2022 for observational studies regarding sarcopenia in liver transplant and mortality. We calculated the risk of mortality in sarcopenia vs. no sarcopenia using the most adjusted estimate available and summarizing the data as risk ratios (RRs) with their 95% confidence intervals (CIs). A random-effect model was considered for all analyses. EVIDENCE SYNTHESIS: Among 1135 studies initially considered, 33 articles were included for a total of 12,137 patients (mean age: 55.3 years; 39.4% females). Over a median of 2.6 years and after adjusting for a median of 3 covariates, sarcopenia increased the risk of mortality approximately 2-fold (RR: 2.01; 95% CI: 1.70-2.36). After accounting for publication bias, the re-calculated RR was 1.75 (95% CI: 1.49-2.06). The quality of the studies was generally low, as determined by the Newcastle Ottawa Scale. CONCLUSIONS: Sarcopenia was significantly linked with an increased risk of mortality in patients listed, evaluated, and undergoing a liver transplantation, indicating the need of interventional studies in this special population with the main aim to reverse this potential reversible condition and decrease mortality risk.

Anticoagulation in atrial fibrillation. A large real-world update.

INTRODUCTION: In a large nationwide administrative database including ∼35 % of Italian population, we analyzed the impact of oral anticoagulant treatment (OAT) in patients with a hospital diagnosis of non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: Of 170404 OAT-naïve patients (mean age 78.7 years; 49.4 % women), only 61.1 % were prescribed direct oral anticoagulants, DOACs, or vitamin-K antagonists, VKAs; 14.2 % were given aspirin (ASA), and 24.8 % no anti-thrombotic drugs (No Tx). We compared ischemic stroke (IS), IS and systemic embolism (IS/SE), intracranial hemorrhage (ICH), major bleeding (MB), major gastro-intestinal bleeding, all-cause deaths and the composite outcome, across four propensity-score matched treatment cohorts with >15400 patients each. Over 2.9±1.5 years, the incidence of IS and IS/SE was slightly less with VKAs than with DOACs (1.62 and 1.84 vs 1.81 and 1.99 events.100 person-years; HR=0.85, 95%CI=0.76-0.95 and HR=0.87, 95%CI=0.78-0.97). This difference disappeared in a sensitivity analysis which excluded those patients treated with low-dose of apixaban, edoxaban, or rivaroxaban (41.7% of DOACs cohort). Compared with DOACs, VKAs were associated with greater incidence of ICH (1.09 vs 0.81; HR=1.38, 95%CI=1.17-1.62), MB (3.78 vs 3.31; HR=1.14, 95%CI=1.02-1.28), all-cause mortality (9.66 vs 10.10; HR=1.07, 95%CI=1.02-1.11), and composite outcome (13.72 vs 13.32; HR=1.04, 95%CI=1.01-1.08). IS, IS/SE, and mortality were more frequent with ASA or No Tx than with VKAs or DOACs (p<0.001 for all comparisons). CONCLUSIONS: Beyond confirming the association with a better net clinical benefit of DOACs over VKAs, our findings substantiate the large proportion of NVAF patients still inappropriately anticoagulated, thereby reinforcing the need for educational programs.

Serial Changes in Cardiopulmonary Exercise Testing Parameters in Untreated Patients With Transthyretin Cardiac Amyloidosis.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is associated with a progressive reduction of functional capacity. The progression of cardiopulmonary exercise testing (CPET) parameters over time is still unknown. METHODS: In this study, 55 patients with ATTR-CM underwent 2 serial cardiologic evaluations and CPETs in a national referral center for cardiac amyloidosis (Careggi University Hospital, Florence). RESULTS: Forty-three patients (78%) had wild-type ATTR. Median age was 80 years (interquartile range [IQR] 76-83 years), and 50 of the patients (91%) were men. At baseline, median peak oxygen consumption (pVO2) was 15 mL/kg/min (IQR 12-18 mL/kg/min), percentage of predicted pVO2 (%ppVO2) was 71% (IQR 60%-83%) and VE/VCO2 slope was 31 (IQR 26-34). After a median follow-up of 14 months (IQR 13-16 months), pVO2, %ppVO2 and VE/VCO2 slope were significantly worsened (-1.29 mL/kg/min [95% confidence interval (CI): -1.85 to -0.74; P < 0.01], -4.5% [95% CI: -6.9 to -2.02; P < 0.01], and 8.6 [95% CI 6-11; P < 0.01], respectively). Furthermore, exercise time (-39 s, 95% CI: -59 to -19; P < 0.01), exercise tolerance (-0.47 metabolic equivalents, 95% CI: -0.69 to -0.2; P < 0.01), and peak systolic pressure (-10.8 mm Hg, 95% CI: -16.2 to -5.4; P < 0.01) were significantly reduced. The worsening in CPET variables did not correspond with a significant change in echocardiographic parameters. CONCLUSIONS: Cardiorespiratory response to exercise significantly worsened over a short period of time in patients with ATTR-CM. Serial CPET may be useful to identify early disease progression.

Prevalence and correlates of frailty in older hypertensive outpatients according to different tools: the HYPER-FRAIL pilot study.

OBJECTIVES: To date, few studies have investigated frailty in hypertensive individuals. This study aimed at identifying the prevalence of frailty in a sample of hypertensive older outpatients using six different identification tools. Clinical correlates of frailty and agreement between different frailty definitions were also investigated. METHODS: The HYPER-FRAIL pilot study recruited hypertensive patients aged at least 75 years from two geriatric outpatient clinics of Careggi Hospital, Florence, Italy. Four frailty scales [Fried Frailty Phenotype, Frailty Index, Clinical Frailty Scale (CFS), Frailty Postal Score] and two physical performance tests [Short Physical Performance Battery (SPPB) and usual gait speed] were applied. The Cohen's kappa coefficient was calculated to assess agreement between measures. Multiple logistic regression was used to identify clinical features independently associated with frailty. RESULTS: Among 121 participants (mean age 81, 60% women), frailty prevalence varied between 33 and 50% according to the tool used. Moderate agreement was observed between Fried Frailty Phenotype, Frailty Index and SPPB, and between Frailty Index and CFS. Agreement was minimal or weak between the remaining measures (K < 0.60). Use of walking aids and depressive symptoms were independently associated with frailty, regardless of the definition used. Frailty correlates also included dementia, disability and comorbidity burden, but not office and 24-h blood pressure values. CONCLUSION: Frailty is highly prevalent among older hypertensive outpatients, but agreement between different frailty tools was moderate-to-weak. Longitudinal studies are needed to assess the prognostic role of different frailty tools and their clinical utility in the choice of antihypertensive treatment.

Survival and Results after Resection and Reconstruction with Megaprosthesis at the Hip in Octogenarians.

Few data are available about results after procedures of resection and megaprosthesis at the hip in very elderly patients. The aim of our study was to ascertain survival and complications in patients aged 80 or older undergoing these major orthopedic procedures. A consecutive series of 27 procedures in 26 patients aged 80-93 years was evaluated. In total, 15 procedures were performed due to oncological diseases, 6 were performed following joint arthroplasty failures or periprosthetic fractures, and 6 were performed after trauma or trauma sequelae. Survival of the patients ranged from 0 to 122 months. Overall survival was 56% at 3 years, 24% at 5 years, and 16% at 8 years. An early postoperative death during the first 3 months occurred in five patients (18.5%). The only preoperative parameter negatively affecting survival was preoperative hemoglobin lower than 11 g/dL. Local complications were similar to reported rates in all-age patients' series. In our experience, resection and megaprosthetic reconstruction can also be a valid choice in very elderly patients, with 56% of patients living more than two years from surgery and 24% more than five. Nevertheless, early postoperative deaths are frequent. A multidisciplinary evaluation of frailty of the patient must be accomplished, and patients and relatives must be informed about the risks of the procedure.