Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality.
ABSTRACT: BACKGROUND:Blood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target <120 mmHg. However, all-cause mortality by attained BP in routine care in frail adults aged above 75 is unclear. OBJECTIVES:To estimate observational associations between baseline BP and mortality/cardiovascular outcomes in a primary-care population aged above 75, stratified by frailty. METHODS:Prospective observational analysis using electronic health records (clinical practice research datalink, n =?415,980). We tested BP associations with cardiovascular events and mortality using competing and Cox proportional-hazards models respectively (follow-up ?10 years), stratified by baseline electronic frailty index (eFI: fit (non-frail), mild, moderate, severe frailty), with sensitivity analyses on co-morbidity, cardiovascular risk and BP trajectory. RESULTS:Risks of cardiovascular outcomes increased with SBPs >150 mmHg. Associations with mortality varied between non-frail <85 and frail 75-84-year-olds and all above 85 years. SBPs above the 130-139-mmHg reference were associated with lower mortality risk, particularly in moderate to severe frailty or above 85 years (e.g. 75-84 years: 150-159 mmHg Hazard Ratio (HR) mortality compared to 130-139: non-frail HR?=?0.94, 0.92-0.97; moderate/severe frailty HR?=?0.84, 0.77-0.92). SBP <130 mmHg and Diastolic(D)BP <80 mmHg were consistently associated with excess mortality, independent of BP trajectory toward the end of life. CONCLUSIONS:In representative primary-care patients aged ?75, BP <130/80 was associated with excess mortality. Hypertension was not associated with increased mortality at ages above 85 or at ages 75-84 with moderate/severe frailty, perhaps due to complexities of co-existing morbidities. The priority given to aggressive BP reduction in frail older people requires further evaluation.
Project description:Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease (CVD) and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre-frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10-fold) and peripheral blood (>200-fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multi-domain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1-year follow-up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro-inflammatory cytokines in pre-frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes. Overall design: mRNA profiles of cd34+ cell from bone marrow and peripherical blood in patients with different fragility index
Project description:Frailty is a common geriatric syndrome characterized by increased risk of disability, hospitalization, and mortality. Hypertension (HTN) is one of the most common chronic medical conditions in the elderly. However, there have been few studies regarding the association between frailty and HTN prevalence, treatment, and control rates. We analyzed data of 4,352 older adults (age ≥ 65 years) from the fifth Korea National Health and Nutrition Examination Survey. We constructed a frailty index based on 42 items and classified participants as robust, pre-frail, or frail. Of the subjects, 2,697 (62.0%) had HTN and 926 (21.3%) had pre-HTN. Regarding frailty status, 721 (16.6%), 1,707 (39.2%), and 1,924 (44.2%) individuals were classified as robust, pre-frail and frail, respectively. HTN prevalence was higher in frail elderly (67.8%) than pre-frail (60.8%) or robust elderly (49.2%) (P < 0.001). Among hypertensive patients, frail elderly were more likely to be treated than pre-frail or robust elderly (P < 0.001), but the proportion of patients whose blood pressure was under control ( < 150/90 mmHg) was lower in frail elderly (P = 0.005). Considering the adverse cardiovascular outcomes associated with frailty, more attention should be paid to the blood pressure control of the frail elderly.
Project description:OBJECTIVES:Frailty is a major clinical geriatric syndrome associated with serious adverse events including functional disability, falls, hospitalisation, increased morbidity and mortality. The aim of this study was to study the associations between frailty defined as Program of Research to Integrate Services for the Maintenance of Autonomy (PRISMA-7) score ?3?and use of healthcare resources in hospital and in the municipality as well as association between frailty and mortality. DESIGN:Register-based retrospective study. SETTING:The target population consists of patients aged 75 years or above who, during hospital stay, were assessed by a physiotherapist, and at discharge from hospital were prescribed further physical training in the community. PARTICIPANTS:973 individuals aged 75+ years were included. OUTCOME MEASURES:We examined associations between frailty and use of healthcare resources in hospital and in the municipality as well as the association between frailty and mortality. RESULTS:973 individuals aged 75+ years were included. Of these, 63.9% had a PRISMA-7 score ?3?and were thus defined as frail. Frail individuals were older compared with non-frail with mean ages of 84.6 and 80.4 years, respectively, p>0.001. Age and gender-adjusted mortality after 1?year was higher among the frail (OR 2.46, 95% CI 1.53 to 3.97). Use of healthcare services in the municipality as well as hospital admissions was significantly higher among frail individuals. CONCLUSIONS:Based on these findings we consider PRISMA-7 to be useful in an in-hospital setting as a screening tool to identify frail elderly patients who may profit from further geriatric assessment during hospital stay. TRIAL REGISTRATION NUMBER:ID REG-070-2017.
Project description:As glucagon-like peptide-1 receptor agonists lower blood pressure (BP) in type 2 diabetes mellitus (T2DM), we examined BP control in relation to targets set by international bodies prior to randomization in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial.We analyzed baseline data from LEADER (NCT01179048), an ongoing phase 3B, randomized, double-blind, placebo-controlled cardiovascular outcomes trial examining the cardiovascular safety of the glucagon-like peptide-1 receptor agonist liraglutide in 9340 people with T2DM from 32 countries [age (all mean?±?SD) 64?±?7.2 years, BMI 32.5?±?6.3?kg/m, duration of diabetes 12.7?±?8.0 years], all of whom were at high risk for cardiovascular disease (CVD).A total of 81% (n?=?7592) of participants had prior CVD and 90% (n?=?8408) had a prior history of hypertension. Despite prescription of multiple antihypertensive agents at baseline, only 51% were treated to a target BP of less than 140/85?mmHg and only 26% to the recommended baseline BP target of less than 130/80?mmHg. In univariate analyses, those with prior CVD were prescribed more agents (P?<?0.001) and had lower BP than those without (137?±?18.8/78?±?10.6?mmHg versus 140?±?17.7/80?±?9.9?mmHg; P?<?0.001). In logistic regression analyses, residency in North America (64% treated to <140/85?mmHg; 38% treated to <130/80?mmHg) was the strongest predictor of BP control.These contemporary data confirm that BP remains insufficiently controlled in a large proportion of individuals with T2DM at high cardiovascular risk, particularly outside North America. Longitudinal data from the LEADER trial may provide further insights into BP control in relation to cardiovascular outcomes in this condition.
Project description:BACKGROUND:It is debated whether the treatment goals and decision-making algorithms for elderly patients with hypertension should be the same as those for younger patients. The American and European guidelines leave decisions about antihypertensive treatment in frail, institutionalized patients up to the treating physician. We therefore systematically searched the literature for publications on the phamacotherapy of arterial hypertension in frail patients. METHODS:The MEDLINE, Embase, and Central databases were systematically searched for randomized, controlled trials (RCTs) and non-randomized studies, including observational studies, on the pharmacotherapy of arterial hypertension in elderly patients since the introduction of the concept of frailty, published over the period 1992-2017. RESULTS:Out of 19 282 citations for randomized, controlled trials and 5659 for non-randomized trials and observational studies, four RCTs and three observational studies were included in the further analysis. The included RCTs showed a trend to- wards a benefit from pharmacotherapy of hypertension in frail patients with respect to mortality, cardiovascular disease, functional status, and quality of life. On the other hand, some of the observational studies indicated a lower rate of falls and lower mortality among patients who received no antihypertensive treatment. CONCLUSION:In view of the conflicting findings of RCTs and non-randomized studies, the lower representation of frail subjects in RCTs, and the high risk of bias in non- randomized studies, the findings of the studies included in this review do not enable the formulation of any strictly evidence-based treatment recommendations. As a rule of thumb, the authors propose that a target systolic blood pressure of <150 mmHg should be aimed at in patients whose gait speed is less than 0.8 m/s, while a target range of 130-139 mmHg can be set for patients over age 80 who are no more than mildly frail.
Project description:<h4>Objective</h4>To develop a frailty index (FI) and explore the relationship of frailty to subsequent adverse outcomes on the effectiveness and safety of more intensive control of both blood glucose and blood pressure (BP), among participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.<h4>Research design and methods</h4>Cox proportional hazard models were used to estimate the effectiveness and safety of intensive glucose control and BP intervention according to frailty (defined as FI >0.21) status. The primary outcomes were macro- and microvascular events. The secondary outcomes were all-cause mortality, cardiovascular mortality, severe hypoglycemia, and discontinuation of BP treatment due to hypotension/dizziness.<h4>Results</h4>There were 11,140 participants (mean age, 65.8 years; 42.5% women, 25.7% frail). Frailty was an independent predictor of all primary outcomes and secondary outcomes. The effect of intensive glucose treatment on primary outcomes showed some evidence of attenuation in the frail: hazard ratios for combined major macro- and microvascular events 1.03 (95% CI 0.90-1.19) in the frail versus 0.84 (95% CI 0.74-0.94) in the nonfrail (<i>P</i> = 0.02). A similar trend was observed with BP intervention. Severe hypoglycemia rates (per 1,000 person-years) were higher in the frail: 8.39 (6.15-10.63) vs. 4.80 (3.84-5.76) in nonfrail (<i>P</i> < 0.001). There was no significant difference in discontinuation of BP treatment between frailty groups.<h4>Conclusions</h4>It was possible to retrospectively estimate frailty in a trial population, and this FI identified those at higher risk of poor outcomes. Participants with frailty had some attenuation of benefit from intensive glucose-lowering and BP-lowering treatments.
Project description:BACKGROUND:Little is known about age-specific target blood pressure (BP) in hypertensive patients with diabetes mellitus (DM). The aim of this study was to determine the BP level at the lowest cardiovascular risk of hypertensive patients with DM according to age. METHODS:Using the Korean National Health Insurance Service database, we analyzed patients without cardiovascular disease diagnosed with both hypertension and DM from January 2002 to December 2011. Primary end-point was composite cardiovascular events including cardiovascular death, myocardial infarction and stroke. RESULTS:Of 241,148 study patients, 35,396 had cardiovascular events during a median follow-up period of 10 years. At the age of?<?70 years, the risk of cardiovascular events was lower in patients with BP?<?120/70 mmHg than in those with BP 130-139/80-89 mmHg. At the age of???70, however, there were no significant differences in the risk of cardiovascular events between patients with BP 130-139/80-89 mmHg and BP?<?120/70 mmHg. The risk of cardiovascular events was similar between patients with BP 130-139/80-89 mmHg and BP 120-129/70-79 mmHg, and it was significantly higher in those with BP???140/90 mmHg than in those with BP 130-139/80-89 mmHg at all ages. CONCLUSIONS:In a cohort of hypertensive patients who had DM but no history of cardiovascular disease, lower BP was associated with lower risk of cardiovascular events especially at the age of?<?70. However, low BP?<?130-139/80-89 mmHg was not associated with decreased cardiovascular risk, it may be better to keep the BP of 130-139/80-89 mmHg at the age of???70.
Project description:Masked uncontrolled hypertension (MUCH) is diagnosed in patients treated for hypertension who are normotensive in the clinic but hypertensive outside. In this study of 333 veterans with CKD, we prospectively evaluated the prevalence of MUCH as determined by ambulatory BP monitoring using three definitions of hypertension (daytime hypertension ?135/85 mmHg; either nighttime hypertension ?120/70 mmHg or daytime hypertension; and 24-hour hypertension ?130/80 mmHg) or by home BP monitoring (hypertension ?135/85 mmHg). The prevalence of MUCH was 26.7% by daytime ambulatory BP, 32.8% by 24-hour ambulatory BP, 56.1% by daytime or night-time ambulatory BP, and 50.8% by home BP. To assess the reproducibility of the diagnosis, we repeated these measurements after 4 weeks. Agreement in MUCH diagnosis by ambulatory BP was 75-78% (? coefficient for agreement, 0.44-0.51), depending on the definition used. In contrast, home BP showed an agreement of only 63% and a ? coefficient of 0.25. Prevalence of MUCH increased with increasing clinic systolic BP: 2% in the 90-110 mmHg group, 17% in the 110-119 mmHg group, 34% in the 120-129 mmHg group, and 66% in the 130-139 mmHg group. Clinic BP was a good determinant of MUCH (receiver operating characteristic area under the curve 0.82; 95% confidence interval 0.76-0.87). In diagnosing MUCH, home BP was not different from clinic BP. In conclusion, among people with CKD, MUCH is common and reproducible, and should be suspected when clinic BP is in the prehypertensive range. Confirmation of MUCH diagnosis should rely on ambulatory BP monitoring.
Project description:The objective of this study was to compare the diagnostic accuracy of office blood pressure (BP) threshold of 140/90 and 130/80 mmHg for correctly identifying uncontrolled out-of-office BP in apparent treatment-resistant hypertension (aTRH). We analyzed 468 subjects from a prospectively enrolled cohort of patients with resistant hypertension in South Korea (clinicaltrials.gov: NCT03540992). Resistant hypertension was defined as office BP ≥ 130/80 mmHg with three different classes of antihypertensive medications including thiazide-type/like diuretics, or treated hypertension with four or more different classes of antihypertensive medications. We conducted different types of BP measurements including office BP, automated office BP (AOBP), home BP, and ambulatory BP. We defined uncontrolled out-of-office BP as daytime BP ≥ 135/85 mmHg and/or home BP ≥ 135/85 mmHg. Among subjects with office BP < 140/90 mmHg and subjects with office BP < 130/80 mmHg, 66% and 55% had uncontrolled out-of-office BP, respectively. The prevalence of controlled and masked uncontrolled hypertension was lower, and the prevalence of white-coat and sustained uncontrolled hypertension was higher, with a threshold of 130/80 mmHg than of 140/90 mmHg, for both office BP and AOBP. The office BP threshold of 130/80 mmHg was better able to diagnose uncontrolled out-of-office BP than 140/90 mmHg, and the net reclassification improvement (NRI) was 0.255. The AOBP threshold of 130/80 mmHg also revealed better diagnostic accuracy than 140/90 mmHg, with NRI of 0.543. The office BP threshold of 130/80 mmHg showed better than 140/90 mmHg in terms of the correspondence to out-of-office BP in subjects with aTRH.
Project description:Aims:Hypertension (HTN) is a well-known contributor to cardiovascular disease, including heart failure (HF) and coronary artery disease, and is the leading risk factor for premature death world-wide. A J- or U-shaped relationship has been suggested between blood pressure (BP) and clinical outcomes in different studies. However, there is little information about the significance of BP on the outcomes of patients with coronary artery disease and left ventricular dysfunction. This study aimed to determine the relationship between BP and mortality outcomes in patients with ischaemic cardiomyopathy. Methods and results:The influence of BP during a median follow-up of 9.8?years was studied in a total of 1212 patients with ejection fraction ?35% and coronary disease amenable to coronary artery bypass grafting (CABG) who were randomized to CABG or medical therapy alone (MED) in the STICH (Surgical Treatment for Ischaemic Heart Failure) trial. Landmark analyses were performed starting at 1, 2, 3, 4, and 5?years after randomization, in which previous systolic BP values were averaged and related to subsequent mortality through the end of follow-up with a median of 9.8?years. Neither a previous history of HTN nor baseline BP had any significant influence on long-term mortality outcomes, nor did they have a significant interaction with MED or CABG treatment. The landmark analyses showed a progressive U-shaped relationship that became strongest at 5?years (?2 and P-values: 7.08, P?=?0.069; 8.72, P?=?0.033; 9.86; P?=?0.020; 8.31, P?=?0.040; 14.52, P?=?0.002; at 1, 2, 3, 4, and 5-year landmark analyses, respectively). The relationship between diastolic BP (DBP) and outcomes was similar. The most favourable outcomes were observed in the SBP range 120-130, and DBP 75-85?mmHg, whereas lower and higher BP were associated with worse outcomes. There were no differences in BP-lowering medications between groups. Conclusion:A strong U-shaped relationship between BP and mortality outcomes was evident in ischaemic HF patients. The results imply that the optimal SBP might be in the range 120-130?mmHg after intervention, and possibly be subject to pharmacologic action regarding high BP. Further, low BP was a marker of poor outcomes that might require other interactions and treatment strategies. Clinical Trial Registration:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.