Search

Background The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals. Methods This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models. Results We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3–3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (p interaction < .05). Conclusions There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial.Methods: In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data.Results: Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96-1.13; frailty index HR: 1.03, 95% CI 0.97-1.09). The proportion of individuals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups.Conclusions: Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty. [ABSTRACT FROM AUTHOR]

The term thiazide is universally understood to refer to diuretics that exert their principal action in the distal tubule. The thiazide class is heterogenous and can be further subdivided into compounds containing the benzothiadiazine ring structure—the thiazide-type (e.g. hydrochlorothiazide)—and those lacking the benzothiadiazine ring—the thiazide-like (e.g. chlorthalidone and indapamide) drugs. Thiazide-like agents are longer acting and constitute the diuretics used in most of the cardiovascular outcome trials that established benefits of treatment with diuretics, but pragmatic aspects, such as lack of availability in convenient formulations, limit their use. Regardless of class heterogeneity, thiazides have retained importance in the management of hypertension for over 60 years. They are reliably effective as monotherapy in a majority of hypertensive patients, and augment the efficacy of other classes of antihypertensives when used in combination. Importantly, a thiazide-based treatment regimen lowers cardiovascular events, and their sturdy effect reinforces their place among the recommended first-line agents to treat hypertension in major domestic and international hypertension guidelines. There are few head-to-head comparisons within the class, but potential differences have been explored indirectly as well as in non-blood pressure mechanisms and potential pleiotropic properties. Until proven otherwise, the importance of these differences remains speculative, and clinicians should assume that cardiovascular events will be lowered similarly across agents when equivalent blood pressure reduction occurs. Thiazides remain underutilized, with only about one-third of hypertensive patients receiving them. For many patients, however, a thiazide is an indispensable component of their regimen to achieve adequate blood pressure control. [ABSTRACT FROM AUTHOR]

Background Whether long-term blood pressure variability (BPV) predicts kidney function decline in generally healthy older adults is unknown. We investigated this association in ASPirin in Reducing Events in the Elderly (ASPREE) trial participants. Methods Between 2010 and 2014, Australian and US individuals aged ≥70 years (≥65 if US minority) were recruited and followed with annual study visits for a median of 4.7 years. Time-to-event analyses and linear mixed effects models were used to examine associations between incident chronic kidney disease (CKD), and trajectories of estimated glomerular filtration rate (eGFR) and log albumin–creatinine ratio (log ACR) with systolic BPV as a continuous measure, and, by tertile of SD of systolic blood pressure (BP). BPV was estimated using systolic BP measures from baseline through the second annual visit, and kidney outcomes were assessed following this period. Results Incident CKD occurred in 1,829 of 6,759 participants (27.2%), and more commonly in BPV tertiles 2 (27.4%) and 3 (28.3%) than tertile 1 (25.5%); however, the risk was not significantly increased after covariate adjustment (tertile 3 hazard ratio = 1.02; 95% confidence interval: 0.91–1.14). Analysis of eGFR (n = 16,193) and log ACR trajectories (n = 15,213) showed individuals in the highest BPV tertile having the lowest eGFR and highest log ACR, cross-sectionally. However, the trajectories of eGFR and log ACR did not differ across BPV tertiles. Conclusions CKD and markers of reduced kidney function occur more commonly in individuals with higher BPV; however, BPV does not influence trajectory of decline in kidney function over time in older adults who are in generally good health. Clinical trials registration Trial Number NCT01038583 and ISRCTN83772183. [ABSTRACT FROM AUTHOR]

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65-98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07-.14) at baseline, and the prevalence of frailty (FI > .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = -.31) and grip strength (r = -.46), and strongly associated with a modified Fried's frailty phenotype (p < .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual's vulnerability to and risk of disease. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults.Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.Results: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12).Discussion: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability. [ABSTRACT FROM AUTHOR]

BACKGROUND Despite readily available treatments, control of blood pressure (BP) with population aging remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both "untreated" and "treated but uncontrolled" high BP. METHODS We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and United States (US) in the ASPirin in Reducing Events in the Elderly study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mm Hg and/or the use of any BP lowering medication. "Controlled hypertension" was defined if participants were receiving antihypertensive medication and BP <140 and 90 mm Hg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control. RESULTS Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP ≥140/90 mm Hg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to "treated but uncontrolled" BP included older age, male, Black race (vs. White), using antihypertensive monotherapy (vs. multiple) and residing in Australia (vs. US). CONCLUSIONS High levels of "untreated" and "treated but uncontrolled" BP occur in healthy elderly people without CVD, suggesting there are opportunities for better BP control in the primary prevention of CVD in this population. CLINICAL TRIALS REGISTRATION NCT01038583. [ABSTRACT FROM AUTHOR]

Background: There are no primary prevention trials of aspirin with relevant geriatric outcomes in elderly people. ASPirin in Reducing Events in the Elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin that will determine whether 5 years of daily 100-mg enteric-coated aspirin extends disability-free and dementia-free life in a healthy elderly population and whether these benefits outweigh the risks.Methods: Set in primary care, this randomized double-blind placebo-controlled trial has a composite primary endpoint of death, incident dementia or persistent physical disability. Participants aged 70+ years (non-minorities) or 65+ years (U.S. minorities) were free of cardiovascular disease, dementia, or physical disability and without a contraindication to, or indication for, aspirin. Baseline data include physical and lifestyle, personal and family medical history, hemoglobin, fasting glucose, creatinine, lipid panel, urinary albumin:creatinine ratio, cognition (3MS, HVLT-R, COWAT, SDMT), mood (CES-D-10), physical function (gait speed, grip strength), Katz activities of daily living and quality of life (SF-12).Results: Recruitment ended in December 2014 with 16,703 Australian and 2,411 U.S. participants, a median age of 74 (range 65-98) years and 56% women. Approximately 55% of the U.S. cohort were from minority groups; 9% of the total cohort. Proportions with hypertension, overweight, and chronic kidney disease were similar to age-matched populations from both countries although lower percentages had diabetes, dyslipidemia, and osteoarthritis.Discussion: Findings from ASPREE will be generalizable to a healthier older population in both countries and will assess whether the broad benefits of daily low-dose aspirin in prolonging independent life outweigh the risks. [ABSTRACT FROM AUTHOR]

Purpose. The results of an evaluation of the impact of restoring sinus rhythm on warfarin sensitivity are reported. Methods. A retrospective review of the records of all patients (n = 46) with atrial fibrillation or flutter who underwent cardioversion or ablation procedures to restore sinus rhythm at a large medical center during a 27-month period was conducted. Patient data covering the 3-month periods before and after the procedures were reviewed to identify the warfarin doses required to maintain International Normalized Ratio (INR) values in the recommended range of 2.0-3.0. Within-individual preprocedure and postprocedure mean weekly warfarin doses for two periods (zero to four weeks and an expanded period of four weeks-3 months) were compared using paired t tests. Results. The average weekly warfarin dose during the four-week preprocedure period was not significantly different from the doses during the four-week and expanded postprocedure periods. The average weekly doses during the four-week and expanded postprocedure periods were significantly less than those used in the expanded preprocedure period (p = 0.004 and p = 0.046, respectively). Conclusion. Warfarin dosages required to maintain a goal INR of 2.0.3.0 were relatively stable in the four weeks before and after procedures to convert atrial fibrillation or flutter to sinus rhythm. Changes in the weekly warfarin dose requirement of ≥10% after the procedures were implemented in a small proportion of patients. The mean weekly warfarin dose was significantly lower in the three months after than in the three months before the procedure. [ABSTRACT FROM AUTHOR]

BackgroundEvidence supporting the benefit of low-dose thiazide-based regimens to reduce cardiovascular events is primarily derived from studies using chlorthalidone, yet low-dose hydrochlorothiazide (HCTZ) (12.5–25 mg) remains more widely prescribed. We sought to describe their comparative dose–response relationships for changes in systolic blood pressure (SBP) and potassium.MethodsPubMed from 1948 to July 2008 was systematically searched to identify clinical trials using either HCTZ or chlorthalidone monotherapies. A total of 108 clinical trials with HCTZ and 29 with chlorthalidone were analyzed. Data were pooled to evaluate the effects on SBP and potassium of both drugs throughout their respective dose–response curves. Equivalence analysis was performed for the clinically recommended low-dose range of 12.5–25 mg, grouped by study duration, using the two one-sided tests procedure described by Schuirmann.ResultsWhen evaluated on a milligram-per-milligram basis using pooled data, chlorthalidone generally produces slightly greater reductions in SBP and potassium than HCTZ. In the low-dose range of 12.5–25 mg, equivalence analysis reveals that the reductions in SBP are not equivalent between the two drugs, using upper and lower equivalence bounds of 4 mm Hg. Within the same dosing range, the mean changes in potassium were determined to be equivalent when upper and lower equivalence bounds of 0.29 mEq/l are used.ConclusionsEquivalence analysis using data from several studies suggests that the SBP reductions achieved with HCTZ and chlorthalidone cannot be considered equivalent within the low-dose range currently recommended. However, within this dosing range, reductions in potassium can be considered equivalent.American Journal of Hypertension 2010; doi:10.1038/ajh.2010.1 [ABSTRACT FROM AUTHOR]

Purpose. The relationship among metformin use, plasma lactate levels, and lactic acidosis in patients with type 2 diabetes mellitus and the appropriateness of metformin use in patients with renal dysfunction are discussed. Summary. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes recommends metformin therapy as first-line therapy along with lifestyle modification to treat type 2 diabetes mellitus. Despite this recommendation, metformin may be underutilized due to the fear of metformin-associated lactic acidosis and because its use is contraindicated in patients with renal dysfunction. Several studies have attempted to characterize the relationship among plasma metformin levels, plasma lactate levels, and lactic acidosis. However, a causal relationship between metformin and lactic acidosis has not been definitively established. In the United States, the estimated rate of lactic acidosis among diabetic patients treated with metformin is similar to that of diabetic patients not taking metformin. Despite specific guidelines advising against prescribing metformin in renal dysfunction, published reports indicate that metformin is continued in 25% of patients after the contraindication is discovered. Individual studies point to a possible correlation between metformin levels and plasma lactate levels, but mortality does not appear to correlate with plasma metformin levels. These results indicate that there may not be a direct relationship between plasma lactate and metformin levels. Conclusion. Current studies point to a weak causal relationship between metformin and lactic acidosis. In patients without comorbid conditions that would predispose them to lactic acidosis, elevated serum creatinine levels should be considered a risk factor for the development of lactic acidosis but not an absolute contraindication. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Baseline Characteristics of Participants in the ASPREE (Aspirin in Reducing Events in the Elderly) Study", which appeared in an earlier issue.

The article discusses the psychological effect of ambulatory blood pressure monitoring (ABPM) tool used on hypertension diagnosis and management among patients in the U.S. Study indicates that many patients undergo a psychological benefit from this tool. It suggests that ABPM may serve as a useful component in motivating patients to adopt lifestyle changes.

The article discusses the study that explores the ways on how thiazide-induced hyperglycemia can be prevented. An increased risk of diabetes with several polymorphisms was reported and the effect was only significant with higher dosages of thiazides. It is noted that it is not well defined whether the absolute increase in serum glucose is large enough to increase cardiovascular risk or merely shift the distribution curve to move some patients across the diabetes threshold.

Comments on patient perceptions about drug advertising and prescription-to-nonprescription switches in the U.S. Impact of the issues on consumer behavior; Sources of information regarding prescription drugs; Contribution by increased advertising to increased medication cost.