Twelve hot questions in the management of hypertension in patients aged 80+ years and their answers with the help of the 2023 European Society of Hypertension Guidelines.

Arterial hypertension is a major risk factor for cardiovascular morbidity and mortality, and highly prevalent in older age, underscoring the importance of its appropriate management. The population is ageing at an increasing rate, with those aged 80+ years being the fastest growing population characterized by high heterogeneity in terms of functionality and autonomy. The prevalence of hypertension rises with increasing age, due to a significant increase in SBP largely as a result of age-related stiffening of the aorta and other large arteries, affecting almost 80% of those aged 80+ years. Appropriate management of blood pressure in this population is a priority for clinicians. Frailty is a condition characterized by marked vulnerability to adverse health outcomes and is common among older adults including those with hypertension. Hypertension increases frailty level and at the same time, individuals with increasing frailty present with more drug-related adverse effects meaning they are less tolerant to blood pressure lowering by medication. Thus, frailty is a factor that should be integrated when treating hypertension in this population. The European Society of Hypertension 2023 Guidelines on the management of Hypertension are the first international guidelines to integrate the concept of adapting blood pressure management in older adults according to their frailty/functionality level, and to propose practical tools for the application of this concept in the daily practice of physicians and other healthcare professionals. The present article prepared by the European Society of Hypertension Working Group on Hypertension in Older Adults aims to further address some important aspects mentioned concisely in the 2023 European Society of Hypertension guidelines, in order to help physicians and other healthcare professionals including those practicing in primary care. To this end, this study discusses 12 'hot questions' which are answered with the help of the 2023 European Society of Hypertension Guidelines. We hope the present article and Working Group's actions will contribute to understanding and applying the ideal management of hypertension in this most vulnerable population.

Frailty and Renal Cell Carcinoma: Integration of Comprehensive Geriatric Assessment into Shared Decision-making.

CONTEXT: Frailty, a geriatric syndrome characterized by decreased resilience and physiological reserve, impacts the prognosis and management of older adults significantly, particularly in the context of surgical and oncological care. OBJECTIVE: To provide an overview of frailty assessment in the management of older patients with a renal mass/renal cell carcinoma (RCC), focusing on its implications for diagnostic workup, treatment decisions, and clinical outcomes. EVIDENCE ACQUISITION: A narrative review of the literature was conducted, focusing on frailty definitions, assessment tools, and their application in geriatric oncology, applied to the field of RCC. Relevant studies addressing the prognostic value of frailty, its impact on treatment outcomes, and potential interventions were summarized. EVIDENCE SYNTHESIS: Frailty is a poor prognostic factor and can influence decision-making in the management of both localized and metastatic RCC. Screening tools such as the Geriatric Screening Tool 8 (G8) and the Mini-COG test can aid clinicians to select older patients (ie, aged ≥65 yr) for a further comprehensive geriatric assessment (CGA) performed by dedicated geriatricians. The CGA provides insights to risk stratify patients and guide subsequent treatment pathways. As such, the involvement of geriatricians in multidisciplinary tumor boards emerges as an essential priority to address the complex needs of frail patients and optimize clinical outcomes. Herein, we propose a dedicated care pathway as a first key step to implement frailty assessment in clinical practice and research for RCC. CONCLUSIONS: Frailty has emerged as a crucial factor influencing the management and outcomes of older patients with RCC. Involvement of geriatricians in diagnostic and therapeutic pathways represents a pragmatic approach to screen and assess frailty, fostering individualized treatment decisions according to holistic patient risk stratification. PATIENT SUMMARY: Frailty, a decline in resilience and physiological reserve, influences treatment decisions and outcomes in elderly patients with renal cell carcinoma, guiding personalized care. In this review, we focused on pragmatic strategies to screen patients with a renal mass suspected for renal cell carcinoma, who are older than 65 yr, for frailty and on personalized management algorithms integrating geriatric input beyond patient- and tumor-related factors.

Gender difference in long-term effect of cardiac rehabilitation; data from CRAGE-extra study.

Introduction: The positive effect of cardiac rehabilitation (CR) is demonstrated in younger and older patients. However, it is quite debated whether the beneficial effect is similarly maintained in both genders during follow-up. Aim: to determine if the improvement obtained after CR remained significant at 1-year follow-up in older population, testing the influence of gender on this outcome. Methods: All patients aged 75+ years consecutively referred to Cardiac Rehabilitation outpatient Unit at Careggi University Hospital were screened for eligibility. All patients attended a CR program, based on 5-day-per-week aerobic training sessions for 4 weeks and they were evaluated at the end of CR at 6 and 12 months of follow-up. Results: 361 patients with a mean age 80.6 ± 4.4 years with a complete 1-year follow-up were enrolled in the study, 87.5 % of them had an acute coronary event, and 27.6 % were females. The increase in exercise capacity at the end of CR and at 1-year follow-up was statistically significant (VO2 peak: +8.7 % in males p < 0.001, +8.5 % in females p < 0.001; distance walked at 6-min test: +7.3 % in males p < 0.001, +10.2 % in females p < 0.001, respectively); the trajectory of exercise improvement at 6 and 12 months of FU was similar in men and women without significant decrease (VO2 peak-ml/kg/min: CR discharge vs 1 year FU = 15.2 vs 15,0 p: NS; distance walked-meters: CR discharge vs 1 year FU = 445.5 vs 440.6, p: NS) from end of CR to 1-year. Conclusions: the improvement in exercise tolerance obtained with CR program is still maintained at 1-year FU without significant influence of gender in our very old population.

Comprehensive Geriatric Assessment to Optimize the Management of Older Patients With Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) predominantly affects older adults with multiple chronic conditions, leading to significant physical, cognitive, and emotional challenges. New disease-modifying drugs are effective in early stages, prompting a shift toward comprehensive assessments, including functional capacity and quality of life. However, these assessments may not fully capture the complexity of older ATTR-CA patients, especially regarding frailty and mood disorders, which can influence symptom reporting. Thus, integrating comprehensive geriatric assessment tools into routine clinical practice may be crucial to detect early signs of frailty or functional impairment that could impact outcomes and mitigate futility and ageism in the decision-making process. This review highlights the importance of evaluating multimorbidity, disability, and frailty in older patients with ATTR-CA to optimize management strategies.

A Comprehensive Geriatric Workup and Frailty Assessment in Older Patients with Severe Aortic Stenosis.

Aortic stenosis (AS) represents a notable paradigm for cardiovascular (CV) and geriatric disorders owing to comorbidity. Transcatheter aortic valve replacement (TAVR) was initially considered a therapeutic strategy in elderly individuals deemed unsuitable for or at high risk of surgical valve replacement. The progressive improvement in TAVR technology has led to the need to refine older patients' stratification, progressively incorporating the concept of frailty and other geriatric vulnerabilities. Recognizing the intricate nature of the aging process, reliance exclusively on chronological age for stratification resulted in an initial but inadequate tool to assess both CV and non-CV risks effectively. A comprehensive geriatric evaluation should be performed before TAVR procedures, taking into account both physical and cognitive capabilities and post-procedural outcomes through a multidisciplinary framework. This review adopts a multidisciplinary perspective to delve into the diagnosis and holistic management of AS in elderly populations in order to facilitate decision-making, thereby optimizing outcomes centered around patient well-being.

Risk of Cardiovascular Events in Metabolically Healthy Overweight or Obese Adults: Role of LDL-Cholesterol in the Stratification of Risk.

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged <70 years, high BMI was associated with an increased risk of MACE, whereas among the older subjects it was associated with lower risk. Compared to the group with normal weight/healthy metabolic status, the metabolically healthy participants aged <70 years who were overweight/obese had an increased risk of MACE with an adjusted hazard ratio of 3.81 (95% CI, 1.34-10.85, p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07-6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

Geriatricians' role in the management of aortic stenosis in frail older patients: a decade later.

INTRODUCTION: Increasing evidence supports the implementation of geriatric assessment in the workup of older patients with aortic stenosis (AS). In 2012, an online European survey revealed that geriatricians were rarely involved in the assessment of candidates for transcatheter aortic valve implantation (TAVI). After a "call to action" for early involvement of geriatricians in AS evaluation, the survey was repeated in 2022. Our aim was to investigate whether geriatricians' role changed in the last decade. METHODS: Online survey conducted between December 16th, 2021, and December 15th, 2022. All members of the European Geriatric Medicine Society were invited to participate. The survey included 26 questions regarding geriatricians' experience with AS and TAVI. RESULTS: Among 193 respondents (79.8% geriatricians), 73 (38%) reported to be involved in AS evaluation at least once a week. During 2 years prior to the survey, 43 (22.3%) had referred > 50% of their patients with severe AS for TAVI. Age influenced TAVI referral in a considerable proportion of respondents (36.8%). TAVI candidates were mainly referred to specialised cardiac centres with multidisciplinary teams (91.8%), including (47.2%) or not including (44.6%) a geriatrician. A total of 38.9% of respondents reported to be part of a multidisciplinary heart team. Geriatricians were less frequently involved (37%) than cardiologists (89.6%) and surgeons (53.4%) in pre-procedural TAVI management. Cardiologists were more frequently involved (85.5%) than geriatricians (33.7%) and surgeons (26.9%) in post-procedural management. CONCLUSIONS: Geriatricians' involvement in AS management and multidisciplinary heart teams remains scarce. More efforts should be devoted to implement geriatricians' role in AS decision-making.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

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.

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.

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.

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.