Michelle Canavan

Association of atrial fibrillation with mortality and disability after ischemic stroke.

Objective: We determined whether patient characteristics (age, sex, comorbidities), stroke severity, and quality of care explained a proportion of the association between atrial fibrillation (AF) and increased disability and mortality in patients with acute ischemic stroke. Methods: The study included a prospective cohort of consecutive patients admitted with acute ischemic stroke included in the Registry of the Canadian Stroke Network (July 1, 2003 to March 31, 2008). Multivariable logistic regression analyses were used to determine the magnitude of association between AF and modified Rankin score 4–5 at discharge, 30-day mortality, and 1-year mortality. Results: There were 10,528 patients admitted with acute ischemic stroke. AF was associated with an increased risk of severe disability and mortality, but the magnitude of association was substantially attenuated in the full multivariable models: modified Rankin score 4–5 at discharge (univariate odds ratio [OR] 1.74, 95% confidence interval [CI] 1.57–1.93; multivariable OR 1.19, 95% CI 1.03–1.36), 30-day mortality (univariate OR 2.52, 95% CI 2.25–2.84; multivariable OR 1.36, 95% CI 1.17–1.58), and 1-year mortality (univariate OR 2.41, 95% CI 2.19–2.66; multivariable OR 1.25, 95% CI 1.10–1.42). Older age and increased stroke severity explained most of the association between AF and poor stroke outcomes. We found no association between AF and poor stroke outcomes in patients receiving therapeutic preadmission oral anticoagulant therapy. Conclusions: Older age and increased stroke severity explain most of the association between AF and poorer outcomes after acute ischemic stroke. Nonuse of oral anticoagulant therapy represents the most important modifiable care gap to mitigate the association between AF and poor outcomes after ischemic stroke.

Sodium intake and renal outcomes: a systematic review

BACKGROUND Sodium intake is an important determinant of blood pressure; therefore, reduction of intake may be an attractive population-based target for chronic kidney disease (CKD) prevention. Most guidelines recommend sodium intake of < 2.3 g/day, based on limited evidence. We reviewed the association between sodium intake and renal outcomes. METHODS We reviewed cohort studies and clinical trials, which were retrieved by searching electronic databases, that evaluated the association between sodium intake/excretion and measures of renal function, proteinuria, or new need for dialysis. RESULTS Of 4,337 reviewed citations, seven (n = 8,129) were eligible, including six cohort studies (n = 7,942) and one clinical trial (n = 187). Four studies (n = 1,787) included patients with CKD. All four cohort studies reported that high intake (> 4.6 g/day) was associated with adverse outcomes (vs. moderate/low), while none reported an increased risk with moderate intake (vs. low). Three studies (n = 6,342) included patients without CKD. Two cohort studies (n = 6,155) reported opposing directions of association between low (vs. moderate) sodium intake and renal outcomes, and one clinical trial (n = 187) reported a benefit from low intake (vs. moderate) on proteinuria but an adverse effect on serum creatinine. CONCLUSIONS Available, but limited, evidence supports an association between high sodium intake (> 4.6g/day) and adverse outcomes. However, the association with low intake (vs. moderate) is uncertain, with inconsistent findings from cohort studies. There is urgent need to clarify the long-term efficacy and safety of currently recommended low sodium intake in patients with CKD.

Which Risk Factors Are More Associated With Ischemic Stroke Than Intracerebral Hemorrhage in Patients With Atrial Fibrillation

Background and Purpose— The decision to prescribe oral anticoagulant therapy in patients with atrial fibrillation is based on an assessment of the competing risks of ischemic stroke and major bleeding, of which intracerebral hemorrhage (ICH) is the most important type. We sought to determine the comparative importance of risk factors for ischemic stroke and ICH in patients with acute stroke and atrial fibrillation with particular emphasis on risk factors common to both stroke types. Methods— Consecutive patients with acute ischemic stroke or ICH and atrial fibrillation included in the Registry of the Canadian Stroke Network constituted the cohort. Multivariable logistic regression analysis was used to determine the association between baseline risk factors and presentation with ICH versus ischemic stroke. Risk factors included: (1) those previously reported to be risk factors for both ischemic stroke and major bleeding (particularly ICH) (“shared” risk factors, including age, alcohol, hypertension, diabetes mellitus, renal impairment, prior stroke/transient ischemic attack and preadmission dementia); and (2) other risk factors associated with either stroke subtype alone. Results— A total of 3197 patients presented with atrial fibrillation and acute stroke, of which 12.2% presented with ICH. Of the “shared” risk factors, age (OR, 1.19; 95% CI, 1.06–1.34 per decade) and prior stroke/transient ischemic attack (OR, 1.45; 95% CI, 1.12–1.87) were more associated with ischemic stroke than ICH, whereas a history of hypertension (OR, 0.89; 95% CI, 0.68–1.17), diabetes mellitus (OR 1.23; 95% CI, 0.92–1.64), renal impairment (OR, 1.28; 95% CI, 0.95–1.71), and alcohol intake were not more strongly associated with either stroke subtype. Conclusion— Of the risk factors known to be associated with both ischemic stroke and ICH in patients with atrial fibrillation, we found that none had a stronger association with ICH. Older age was more strongly associated with ischemic stroke than ICH.

Mild chronic kidney disease and functional impairment in community-dwelling older adults

BACKGROUND chronic kidney disease (CKD) has been associated with an increased risk of death and cardiovascular events, but its relationship with non-vascular outcomes, including functional impairment (FI), is less well understood. OBJECTIVE in this study, we review the association between CKD and FI, adjusting for potential confounders and risk factors, with a primary outcome of impairment in any instrumental ADL (IADL) or basic ADL (BADL). DESIGN the Cardiovascular Multimorbidity in Primary Care Study (CLARITY) is a cross-sectional study of community-dwelling adults. SETTING participants were adults living in the West of Ireland attending university-affiliated general practices. SUBJECTS all participants were adults aged ≥50 years living in the community. METHODS CKD was defined as an estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73 m(2). A standardised self-reported health questionnaire to measure activities of daily living (ADL) was completed by participants. Logistic regression analyses were used to determine the independent association between CKD and FI. RESULTS a total of 3,499 patients were included with a mean age of 66.2 ± 10.3 years. 18.0% (n = 630) had CKD (mean eGFR 50.2 ± 9.2 ml/min/1.73m(2)), 21.9% (n = 138) of which had a diagnosis of CKD documented in medical records. 40.4% (n = 1,413) reported FI and multivariable adjustment showed CKD to be independently associated with FI (OR: 1.43, 1.15-1.78), impairment in IADL (OR: 1.43, 1.15-1.78) and impairment in BADL (OR: 1.39, 1.11-1.75). CONCLUSION our study shows even mild CKD is associated with FI, independent of age, gender, co-morbidities, traditional vascular risk factors and cardiovascular events.

Global Survey of the Frequency of Atrial Fibrillation-Associated Stroke: Embolic Stroke of Undetermined Source Global Registry.

Background and Purpose— Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Methods— Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Results— Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6–29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6–12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3–5.4; P<0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). Conclusions— This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women.

Antithrombotic Therapy After Acute Ischemic Stroke in Patients With Atrial Fibrillation

Background and Purpose— For patients with atrial fibrillation and ischemic stroke (IS), current guidelines recommend oral anticoagulation (OAC) alone for secondary prevention of IS. In a large prospective cohort of patients with acute IS and atrial fibrillation, we determine the association between antithrombotic regimen on discharge and risk of major vascular events. Methods— Prospective cohort of consecutive patients included in the Ontario Stroke Registry. Multivariable Cox proportional hazard models were used to determine the association between antithrombotic regimen on discharge and time to death or admission for recurrent IS, myocardial infarction, or major bleeding. Results— Two thousand one hundred sixty-two patients were hospitalized atrial fibrillation and acute IS. At discharge, 8.0% were prescribed no antithrombotic therapy, 21.6% antiplatelet therapy alone, 39.3% OAC (warfarin) alone, and 31.1% combination OAC and antiplatelet therapy. Compared with OAC alone (hazard ratio [HR], 1.0), no antithrombotic therapy (HR, 1.51; 95% confidence interval, 1.23–1.86) and antiplatelet therapy (HR, 1.31; 95% confidence interval, 1.14–1.50) were associated with an increased risk of the primary composite outcome, whereas combination OAC and antiplatelet therapy was associated with a trend toward a reduced risk (HR, 0.91; 95% confidence interval, 0.80–1.04 overall and HR, 0.79; 95% confidence interval, 0.61–1.02 in those with coronary heart disease). Results were consistent in those with severe stroke: HR 1.58 (95% CI, 1.21–2.06), 1.34 (95% CI, 1.09–1.63), and 0.91 (95% CI, 0.74–1.11), respectively. Conclusions— Contrary to current guidelines, 30% of patients with atrial fibrillation and recent IS are not prescribed any OAC therapy on discharge, whereas a further 30% are prescribed combination OAC and antiplatelet therapy. Combination OAC and antiplatelet therapy in patients at high cardiovascular risk requires evaluation in clinical trials, particularly with the newer OACs, given their more favorable risk–benefit ratio compared with warfarin.

Preventing cardiovascular disease in primary care: Role of a national risk factor management program

BACKGROUND Heartwatch, a structured risk factor modification program for secondary prevention of cardiovascular (CV) disease (CVD) in primary care, is associated with improvements in CV risk factors in participating patients. However, it is not known whether Heartwatch translates into reductions in clinically important CV events. OBJECTIVE The aim of the study was to determine the association between participation in Heartwatch and future risk of CV events in patients with CVD. METHODS The study consisted of a prospective cohort of 1,609 patients with CVD in primary care practices. Of these, 97.5% had data available on Heartwatch participation status, of whom 15.2% were Heartwatch participants. Cox proportional hazards models were used to determine the association between Heartwatch participation and risk of the CV composite (CV death, nonfatal myocardial infarction, heart failure, and nonfatal stroke). All-cause mortality and CV mortality were secondary outcome measures. RESULTS During follow-up, the CV composite occurred in 208 patients (13.6%). Of Heartwatch participants, 8.4% experienced the CV composite compared with 14.5% of nonparticipants (P = .003). Participation in Heartwatch was associated with a significantly reduced risk of the CV composite (hazard ratio [HR] 0.52, 95% CI, 0.31-0.87), CV mortality (HR 0.31, 95% CI, 0.11-0.89), and all-cause mortality (HR 0.32, 95% CI, 0.15-0.68). Heartwatch participation was also associated with greater reductions in mean systolic blood pressure (P = .047), mean diastolic blood pressure (P < .001), and greater use of secondary preventative therapies for CVD, such as lipid-lowering agents (P < .001), β-blockers (P < .001), and angiotensin-converting enzyme inhibitors (P < .001). CONCLUSION Heartwatch is associated with a reduced risk of major vascular events and improved risk factor modification, supporting its potential as a nationwide program for secondary prevention of CVD.

Does lowering blood pressure with antihypertensive therapy preserve independence in activities of daily living? A systematic review.

BACKGROUND Hypertension is a major risk factor for functional impairment. Dependence is an important related outcome for older adults, but outcomes in hypertension trials appear to focus primarily on major vascular events. This systematic review had 2 objectives: (i) to determine the proportion of randomized controlled trials (RCTs) evaluating antihypertensive therapies that reported a measure of a persons ability to carry out activities of daily living (ADL) and (ii) to evaluate the effect of blood pressure (BP)-lowering therapies on ability to carry out ADL compared with control therapy. METHODS We searched electronic databases, reference lists of relevant meta-analyses, and hypertension guidelines for clinical trials of adults with hypertension/prehypertension that were randomized to antihypertensive therapy or control for ≥1 year. RESULTS Of 2,924 citations screened, there were 93 eligible RCTs. One (1%) reported ADL as a primary outcome measure. Nine (10%) reported ADL as a secondary outcome. Of these, 6 used validated ADL scales, whereas 4 measured ADL within quality-of-life scales. Six trials with duration of ≥1 year (n = 12,663) were amenable to meta-analysis, despite use of different ADL scales. The odds of having difficulty with ADL was reduced by BP-lowering therapy compared with control therapy (odds ratio = 0.84; 95% confidence interval = 0.77-0.92; I (2) = 0%). CONCLUSIONS We identified few trials of antihypertensive therapy that reported ADL as an outcome measure, with heterogeneity in scales used. Antihypertensive therapy was associated with a lower risk of ADL impairment compared with control therapy. RCTs evaluating the effect of antihypertensive drugs on ADL in older adults with mild hypertension are required.

Vascular risk factors, cardiovascular disease and functional impairment in community-dwelling adults.

Background: Older adults report preservation of functional independence as one of the most important constructs of successful ageing. Vascular risk factors may increase the risk of functional impairment due to clinical and subclinical vascular disease. Objective: To describe the association between vascular risk factors and impaired ability to perform daily living activities, independent of established cardiovascular disease. Methods: We conducted an analysis of the Clarity Cohort, which is a cross-sectional study of 9,816 community-dwelling Irish adults. Of the total cohort, 3,499 completed standardized self-reported health questionnaires, which included questions on activities of daily living. Functional impairment was defined as self-reported impairment in self-care, mobility or household tasks. Using logistic regression analyses, we determined the association between vascular risk factors and functional impairment, independent of demographics, prior coronary artery disease, stroke, congestive heart failure, and peripheral vascular disease. Results: Functional impairment was reported in 40.4% (n = 1,413) of the cohort overall and in 23% of those with established cardiovascular disease. The mean age was 66.2 ± 10.3 years, 52% of the cohort were aged over 65 and 45.6% were male. Some difficulty with instrumental activities of daily living was reported by 35.4% (n = 1,240) while 29.4% (n = 1,029) reported some difficulty with basic activities of daily living. On multivariable analysis, older age [OR 1.03 (1.02, 1.04) per year], current smoking [OR 1.43 (1.08, 1.89)], atrial fibrillation [OR 1.68 (1.07, 2.65)], former alcohol use [OR 1.87 (1.36, 2.57)] and prior stroke [OR 1.91 (1.24, 2.93)] were associated with an increased risk of functional impairment. Older age leaving education [OR 0.96 (0.94, 0.99)], non-use of alcohol [OR 0.76 (0.61, 0.93)] and increased high-density lipoprotein levels [OR 0.70 (0.56, 0.88)] were associated with reduced risk of functional impairment. Conclusions: Independent of established cardiovascular disease, some vascular risk factors are associated with functional impairment. Modification of these risk factors is expected to have a large impact on preservation of functional independence through prevention of overt and covert vascular disease.

A review of Vitamin D insufficiency and its management; a lack of evidence and consensus persists

Vitamin D deficiency is the most common nutritional deficiency worldwide, however uncertainty persists regarding the benefits of vitamin D supplementation. Vitamin D is essential for calcium homeostasis, and has been linked to falls and fractures in older people. There are numerous risk factors for vitamin D deficiency, chief among them old age. Studies of vitamin D supplementation have given mixed signals, but over all there is evidence of benefit for those with risk factors for deficiency. International guidelines recommend vitamin D target levels of >25 to >80 nmol/l, best achieved by a daily dose of 800-1000 IU. Large bolus doses should be avoided. There are still unanswered questions regarding vitamin D supplementation and target levels. There is need for well designed and powered trials to achieve consensus.