Lipoprotein-associated phospholipase A₂ activity and mass in relation to vascular disease and nonvascular mortality

Abstract. Heart Protection Study Collaborative Group (Clinical Trial Service Unit, University of Oxford, Oxford, UK) Lipoprotein‐associated phospholipase A₂ activity and mass in relation to vascular disease and nonvascular mortality. J Intern Med 2010; 268 :348–358. Objectives. To assess whether associations of circulating lipoprotein‐associated phospholipase A₂ (Lp‐PLA₂) with vascular disease are independent of other risk factors. Methods. Lp‐PLA₂ activity and mass, lipids and other characteristics were measured at baseline in 19 037 individuals at high risk of vascular disease in a randomized trial of simvastatin with 5‐year average follow‐up. Results. Lp‐PLA₂ activity and mass were correlated with each other (r = 0.56), lipids and other vascular risk factors. The moderate association of Lp‐PLA₂ activity with occlusive coronary events (n = 2531) in analyses adjusted for nonlipid factors (hazard ratio per 1 SD [HR] 1.11, 95% CI 1.06–1.15) became nonsignificant after further adjustment for apolipoproteins (HR 1.02, 0.97–1.06). Such adjustment also attenuated HRs with Lp‐PLA₂ mass from 1.08 (1.03–1.12) to 1.05 (1.01–1.09). By contrast, the HR with apolipoprotein‐B100 of 1.15 (1.10–1.19) was only slightly attenuated to 1.14 (1.09–1.19) after further adjustment for apolipoprotein A₁ and Lp‐PLA₂. Age‐ and sex‐adjusted HRs for other cardiac events (n = 1007) with either Lp‐PLA₂ activity or mass were about 1.20, but HRs reduced after adjustment for nonlipid factors (activity: 1.11, 1.04–1.18; mass: 1.08, 1.02–1.15). Adjusted HRs for ischaemic stroke (n = 900) were weak and nonsignificant and for nonvascular mortality (n = 1040) were 1.01 (0.94–1.09) with activity and 1.12 (1.05–1.19) with mass. Simvastatin reduced Lp‐PLA₂ levels by about one‐quarter, but simvastatin’s vascular protection did not vary with baseline Lp‐PLA₂ concentration. Conclusions. Associations of Lp‐PLA₂ with occlusive coronary events depend considerably on lipid levels, whereas those with other cardiac events appear to reflect confounding from cardiovascular medication and prior vascular disease.     

Biomarkers of kidney function and prediction of death from cardiovascular and other causes in the elderly: A 9-year follow-up study

BackgroundCystatin C is claimed to be superior to creatinine-based estimates of glomerular filtration rate (eGFRcr). The purpose of the study is to analyze whether cystatin C, creatinine, and/or estimated glomerular filtration rates (eGFR) predicted cardiovascular and/or non-cardiovascular deaths among Finnish elderly.MethodsHazard ratios (HR) of cystatin C, creatinine and eGFRs for cardiovascular and non-cardiovascular deaths.ResultsDuring a 9-year follow-up, 275 died, 192 deaths were a result of cardiovascular disease. In age-adjusted analyses, cystatin C predicted the risk of non-cardiovascular and cardiovascular death in men (HR for 0.1-unit increase 1.12 [95% CI, 1.04–1.19] for non-CVD deaths and 1.18 [1.09–1.28] for CVD deaths) and women (1.14 [1.07–1.21] and 1.14 [1.06–1.22], respectively). CKD-EPIcr-cyc predicted the risk of CVD deaths in men (HR for 5-unit decrease 1.17 [1.09–1.25]) and women (1.09 [1.02–1.17]) and non-CVD deaths in women (1.07 [1.01–1.14]). Also, MDRD (HR for 5-unit decrease 1.16 [1.05–1.27]) and CKD-EPI (HR for 5-unit decrease 1.15 [1.05–1.25]) predicted CVD deaths among men. After additional adjustments, predictive value of cystatin C remained significant. Also, the predictive value of CKD-EPIcr-cys remained significant in non-CVD deaths among women.ConclusionCystatin C was clearly the best predictor for cardiovascular and non-cardiovascular deaths among Finnish elderly. Serum cystatin C is more accurate for clinical decision making than creatinine-based eGFR equations or the combined CKD-EPIcr-cys equation in persons older than 64 years.     

Beta2-microglobulin for risk stratification of total mortality in the elderly population: comparison with cystatin C and C-reactive protein

BACKGROUND: The clinicoepidemiologic relevance of moderately elevated concentrations of circulating beta(2)-microglobulin (beta(2)-M) has not been established. METHODS: We examined whether serum beta(2)-M concentration independently predicts total mortality in community-dwelling older populations and compared its predictive value with that of cystatin C and C-reactive protein (CRP) using a prospective cohort study of 1034 initially nondisabled persons 65 years and older as part of the Tokyo Metropolitan Institute of Gerontology Longitudinal Interdisciplinary Study on Aging. Cox proportional hazards models were used to examine independent associations between baseline beta(2)-M levels and total mortality. RESULTS: During a median follow-up of 7.9 years, 223 persons died. A strong dose-response relationship was found between baseline serum beta(2)-M concentration and mortality risk, even after multiple adjustments. Compared with individuals in the lowest tertile of serum beta(2)-M concentration, those in the middle (hazard ratio, 2.02; 95% confidence interval [CI], 1.35-3.04) and highest (hazard ratio, 2.84; 95% CI, 1.92-4.20) tertiles had a substantially increased mortality risk. Respective values were 1.28 (95% CI, 0.86-1.90) and 1.95 (95% CI, 1.31-2.89) for cystatin C and 1.39 (95% CI, 0.98-1.98) and 1.44 (95% CI, 1.00-2.06) for CRP; only the highest tertiles showed significantly higher mortality risks. The area under the receiver operating characteristic curve for 8-year mortality was greatest for beta(2)-M (0.70; 95% CI, 0.66-0.74), followed by cystatin C (0.66; 95% CI, 0.62-0.70) and CRP (0.57; 95% CI, 0.53-0.61). Additional adjustment for renal function measures, inflammation markers, or both only partially reduced the association between beta(2)-M and mortality. CONCLUSION: Serum beta(2)-M is an independent predictor of total mortality in a general population of older adults and may be a better predictor than cystatin C or CRP.     

Circulating adiponectin levels and mortality in elderly men with and without cardiovascular disease and heart failure

BACKGROUND: High adiponectin levels have been associated with reduced cardiovascular risk but have been shown to predict mortality in those at high risk for vascular disease. We examined the relationship between adiponectin levels and mortality in older men with and without diagnosed cardiovascular disease (CVD) and heart failure. METHODS: Prospective study of 4046 men aged 60 to 79 years drawn from general practices in 24 British towns and followed up for a mean of 6 years, during which 734 deaths occurred. The men were divided into the following groups according to the presence of physician-diagnosed CVD and heart failure: (1) those with no CVD or heart failure; (2) those with CVD but without heart failure; and (3) those with heart failure (with or without CVD). RESULTS: After adjustment for a wide range of baseline characteristics, adiponectin levels were positively associated with significantly increased all-cause and CVD mortality in men with no diagnosed CVD or heart failure (top third vs bottom third adjusted relative risk, 1.55 [95% confidence interval (CI), 1.19-2.02; P = .002 for trend] vs 1.53 [95% CI, 1.03-2.27; P = .02 for trend]), as well as in men with diagnosed heart failure ([adjusted relative risk, 2.37 [95% CI, 0.64-8.79; P = .04 for trend] vs 3.43 [95% CI, 0.54-21.70; P = .008 for trend]). No association was seen in those with diagnosed CVD without heart failure. Adjustment for weight loss and renal function made minor differences to these relationships. CONCLUSIONS: In older men, high adiponectin levels are associated with increased all-cause and CVD mortality in those with heart failure and those free of CVD. Such observations suggest that adiponectin levels may reflect a balance of both protective and harmful factors.     

Self-rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study

Abstract. Grool AM, van der Graaf Y, Visseren FLJ, de Borst GJ, Algra A, Geerlings MI, on behalf of the SMART Study Group (University Medical Center Utrecht, Utrecht, The Netherlands). Self‐rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study. J Intern Med 2012; 272: 277–286. Objectives. Lower self‐rated health status has been associated with worse prognosis in patients with coronary artery disease (CAD). We investigated the influence of self‐rated physical and mental health status on the risk of future vascular events and mortality for various locations of symptomatic atherosclerotic disease and asymptomatic disease. Design. Patients with CAD (n = 2547), cerebrovascular disease (n = 1061), peripheral arterial disease (PAD; n = 648), abdominal aortic aneurysm (AAA; n = 272) and asymptomatic atherosclerotic disease (n = 1933) were followed for a median of 4 years for the occurrence of a new vascular event or death. Self‐rated health status was assessed with the Short Form‐36 physical and mental component summary scales. Cox regression models were used to estimate associations between health status and vascular events and death, adjusted for age, sex, vascular risk factors and intima–media thickness. Results. In the total population, lower self‐rated physical health status (per 10‐point decrease) increased the risk of vascular events [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.24–1.52], and all‐cause (HR = 1.45, 95% CI 1.29–1.63) and vascular mortality (HR = 1.40, 95% CI 1.20–1.64). A 10‐point decrease in mental health status was associated with a modest increase in the risk of vascular events (HR = 1.19, 95% CI 1.08–1.32), and all‐cause (HR = 1.19, 95% CI 1.05–1.34) and vascular mortality (HR = 1.28, 95% CI 1.09–1.49). Risk estimates of physical and mental health status were highest in patients with asymptomatic atherosclerotic disease and lowest in those with PAD. Conclusions. Poorer self‐rated physical and mental health status increases the risk of vascular events and mortality in a broad population of patients with symptomatic and asymptomatic atherosclerotic disease.     

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study

BACKGROUND: The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people.SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level.RESULTS: During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7).CONCLUSION: Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.     

Impact of contrast-induced nephropathy and cardiovascular events by serum cystatin C in renal insufficiency patients undergoing cardiac catheterization

We assessed the usefulness of serum cystatin C for predicting contrast-induced nephropathy (CIN) in patients (n = 100) undergoing coronary catheterization. After a 12-month follow-up, the incidence of CIN was 8.3% (n = 5) in patients with mild renal insufficiency (estimated glomerular filtration rate [eGFR] 60-89 mL/min per 1.73 m2), 34.4% (n = 10) in those with moderate renal insufficiency (eGFR 30-59 mL/min per 1.73 m2), and 100% (n = 3) in those with severe renal insufficiency (eGFR 15-29 mL/min per 1.73 m2). The sensitivity was 81.8% and specificity was 90.9% at the cutoff level of serum cystatin C >1.18 mg/L. Serum cystatin C levels were significantly (P < .001) higher in the patients with moderate renal insufficiency in the CIN group than those in the non-CIN group. Multivariate logistic regression analysis demonstrated that baseline serum cystatin C independently predicted short-term mortality (odds ratio [OR], 0.311; 95% confidence interval [CI] 0.058-0.538; P = .026). Baseline serum cystatin C significantly predicted the occurrence of CIN in the patients with moderate renal insufficiency.     

Prospective Study of Serum 25-Hydroxyvitamin D Level, Cardiovascular Disease Mortality, and All-Cause Mortality in Older U.S. Adults

OBJECTIVES: To evaluate the association between serum 25‐hydroxyvitamin D (25(OH)D) levels and mortality in a representative U.S. sample of older adults. DESIGN: Prospective cohort from the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality files. SETTING: Noninstitutionalized U.S. civilian population. PARTICIPANTS: Three thousand four hundred eight NHANES III participants aged 65 and older enrolled from 1988 to 1994 and followed for mortality through 2000. MEASUREMENTS: Primary exposure was serum 25(OH)D level at enrollment. Primary and secondary outcomes were all‐cause and cardiovascular disease (CVD) mortality, respectively. RESULTS: During the median 7.3 years of follow‐up, there were 1,493 (44%) deaths, including 767 CVD‐related deaths. Median 25(OH)D level was 66 nmol/L. Adjusting for demographics, season, and cardiovascular risk factors, baseline 25(OH)D levels were inversely associated with all‐cause mortality risk (adjusted hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.98, per 10 nmol/L 25[OH]D). Compared with subjects with 25(OH)D levels of 100 nmol/L or higher, the adjusted HR for subjects with levels less than 25.0 nmol/L was 1.83 (95% CI=1.14–2.94) and for levels of 25.0 to 49.9 nmol/L was 1.47 (95% CI=1.09–1.97). The association appeared stronger for CVD mortality (adjusted HR=2.36, 95% CI=1.17–4.75, for subjects with 25[OH]D levels<25.0 nmol/L vs those ≥100.0 nmol/L) than for non‐CVD mortality (adjusted HR=1.42, 95% CI=0.73–2.79, for subjects with 25[OH]D levels<25.0 nmol/L vs those ≥100.0 nmol/L). CONCLUSION: In noninstitutionalized older adults, a group at high risk for all‐cause mortality, serum 25(OH)D levels had an independent, inverse association with CVD and all‐cause mortality. Randomized controlled trials of vitamin D supplementation in older adults are warranted to determine whether this association is causal and reversible.     

Serum concentrations of 17β-E2 and 25-hydroxycholecalciferol (25OHD) in relation to all-cause mortality in older men – the MINOS study

Objective To examine the association of serum hormone levels with all‐cause mortality in older community‐dwelling men. Design Single centre cohort study. Subjects Men aged 50 and older, insured by Société de Secours Minière de Bourgogne (Montceau les Mines, France). Among 3400 men invited to participate, 782 volunteers had serum hormone measurements and were followed up for 10 years. No exclusion criteria were used. Results Nonsurvivors (n = 182) were older, had more comorbidities and lower physical performance. The lowest quartile of 25‐hydroxycholecalciferol (25OHD) level predicted mortality [HR = 1·44, 95% confidence interval (CI): 1·03–2·03, P < 0·05] regardless of age, BMI, smoking, physical activity, vitamin D supplementation, and health status; mainly for the first 3 years. The 17β‐E₂ level predicted mortality independent of confounders after the third year (HR = 1·21 per 1 SD increase, 95% CI: 1·09–1·35, P < 0·001). In the fully adjusted models, risk of death increased per quartiles of 17β‐E₂ (trend –P < 0·001) and was higher in the third and the fourth quartiles compared with the lowest quartile (HR = 1·80, 95% CI: 1·09–2·98, P < 0·05 and HR = 2·83, 95% CI: 1·71–4·67, P < 0·001). Concentrations of testosterone and PTH did not predict mortality independent of the model. Conclusions In older men, increased 17β‐E₂ level predicted mortality after 3 years of follow‐up. Thus, high 17β‐E₂ level may reflect presence of risk factors precipitating development of diseases. Low 25OHD level predicted mortality more weakly, mainly for the first 3 years of the follow‐up, and was strongly influenced by the confounding variables. Thus, low 25OHD level may reflect poor current health status and unhealthy lifestyle.     

Depressive symptoms and development of coronary heart disease events: the Italian longitudinal study on aging

BACKGROUND: Studies on the association between depressive symptomatology (DS) and cardiovascular events and mortality in elderly persons have yielded contradictory findings. To address this issue, the authors assessed DS and an extensive array of sociodemographic, behavioral, and biological variables in the largest population-based sample of older Italians ever studied and analyzed their association with coronary heart disease (CHD) morbidity and total number of deaths. METHODS: This prospective, community-based cohort study included a sample of 5632 Italians, 65 years and older, who were recruited from the demographic registries of eight municipalities in Italy. Depressive symptomatology was assessed using the Geriatric Depression Scale, and a score > or =10 was used to indicate the presence of DS. All traditional cardiovascular disease risk factors were assessed at baseline, through questionnaires, blood tests, and physical examinations. The outcomes were CHD fatal and nonfatal events and total number of deaths. The association of the predictive variables with the outcomes was assessed using different Cox models. RESULTS: Baseline DS was associated with a higher incidence of fatal and nonfatal CHD events (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.06-2.60) and with cardiovascular mortality in men (HR, 2.49; 95% CI, 1.60-3.87) and with total mortality in men (HR, 2.02; 95% CI, 1.58-2.58) and women (HR, 1.43; 95% CI, 1.04-1.95) at the 4-year follow-up assessment. This association was observed after adjusting for a vast array of potential confounding variables, including major chronic conditions. CONCLUSIONS: Depressive symptomatology confers an increased risk for CHD in men and for total mortality in men and women but is not explained by health behaviors, social isolation, or biological or clinical determinants.     

Association between depression and mortality in older adults: the Cardiovascular Health Study

BACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals. OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors. METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality. RESULTS: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46). CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.     

Prospective study of alcohol consumption in the United States: quantity, frequency, and cause-specific mortality

Background: Alcohol average volume (quantity multiplied by frequency) has been associated with mortality in drinkers. However, average volume may mask associations due to quantity or frequency alone. Methods: We prospectively assessed relationships between alcohol quantity and frequency, and mortality from all‐causes, cardiovascular disease, cancer, and other‐causes in a cohort created by linking the 1988 National Health Interview Survey (response rate 87%) to the National Death Index through 2002. Participants were 20,765 current drinkers age ≥ 18 years. At 14‐year follow‐up 2,547 had died. Results: For quantity, among men who consumed ≥5 drinks (compared to 1 drink) on drinking days, adjusted relative risks (RR) of mortality were: for cardiovascular disease, 1.30 [95% confidence interval (CI) 0.96–1.75; p for linear trend (p‐trend) = 0.0295], for cancer, 1.53 (95% CI 1.11–2.09; p‐trend = 0.0026), and for other‐causes, 1.42 (95% CI 1.08–1.87; p‐trend = 0.0029); among women for other‐causes, 2.88 (95% CI 1.61–5.12; p‐trend = 0.0010). For frequency, among men in the highest frequency quartile (compared to the lowest), RR were: for cardiovascular disease, 0.79 (95% CI 0.63–0.99; p‐trend = 0.0330), for cancer, 1.23 (95% CI 0.95–1.59; p‐trend = 0.0461), and for other‐causes, 1.30 (95% CI 1.01–1.67; p‐trend = 0.0070); among women, for cancer, 1.65 (95% CI 1.12–2.45, p‐trend = 0.0031). Average volume obscured effects of quantity alone and frequency alone, particularly for cardiovascular disease in men where quantity and frequency trended in opposite directions. Conclusions: Alcohol quantity and frequency were independently associated with cause‐specific mortality. Accumulating evidence of their differential effects may, in the future, be useful for clinical and public health recommendations.     

Relationship of abnormal heart rate turbulence and elevated CRP to cardiac mortality in low, intermediate, and high-risk older adults

HRT and CRP for Mortality Risk in Elderly. Introduction: We examined whether heart rate turbulence (HRT) and C‐reactive protein (CRP) add to traditional risk factors for cardiac mortality in older adults at low, intermediate, and high risk. Methods and Results: One thousand two hundred and seventy‐two individuals, age ≥65 years, with 24‐hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated CRP (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical cardiovascular disease. Having TS + TO abnormal compared to both normal was associated with cardiac mortality in the low‐risk group [HR 7.9, 95% confidence interval (CI) 2.8–22.5, (P < 0.001)]. In the high and intermediate risk groups, abnormal TS and TS + TO ([HR 2.2, 95% CI 1.5–4.0, P = 0.016] and [HR 2.7, 95% CI 1.2–5.9, P = 0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low‐risk individuals [HR 2.5, 95% CI 1.3–5.1, P = 0.009]. Among low risk, the c‐statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT. Conclusions: Abnormal HRT independently adds to risk stratification of low, intermediate and high‐risk individuals, but HRT and CRP appear to both add to stratification of those considered low risk . (J Cardiovasc Electrophysiol, Vol. 22, pp. 122‐127, February 2011)     

Prevalence of markers of heart failure in patients with atrial fibrillation and the effects of ximelagatran compared to warfarin on the incidence of morbid and fatal events: a report from the SPORTIF III and V trials

BACKGROUND: Patients with atrial fibrillation (AF) who also have heart failure have a worse outcome but the diagnosis of heart failure is often missed. AIM: To compare the effects of warfarin and ximelagatran on morbidity and mortality in patients with AF with and without markers of heart failure. METHODS AND RESULTS: Data for 7329 patients from two randomised controlled trials were merged. Treatment with loop diuretics or the presence of left ventricular dysfunction, were used as markers of possible heart failure. The 3555 (49%) patients with markers of heart failure had higher composite event rates on warfarin (10.81% per year [py] [95% CI 9.59 to 12.13]) compared to the 3774 (51%) patients without markers of heart failure (4.18% py [95% CI 3.44 to 5.01]). The composite event rate was lower on ximelagatran overall (6.18% py [95% CI 5.51 to 6.89] versus 7.34% py [95% CI 6.63 to 8.10] on warfarin; P=0.0219 for the difference) with similar effects in each trial and in patients with and without markers of heart failure, mainly due to fewer heart-failure events (hazard ratio 0.69 [95% CI 0.54 to 0.87]; P<0.001). CONCLUSIONS: Patients with markers of heart failure, even if the diagnosis is not well established, are at increased risk of thromboembolic events and might be targeted for more effective antithrombotic therapy. This might include patients in sinus rhythm as well as AF.     

Advanced chronic kidney disease: Relationship to outcomes post‐TAVR,a meta‐analysis

Chronic kidney disease (CKD) is associated with worse outcomes in high‐surgical‐risk patients undergoing transcatheter aortic valve replacement (TAVR). However, it is unclear whether this relationship is apparent in lower‐surgical‐risk patients. We sought to analyze existing literature to assess whether or not advanced CKD is associated with increased mortality or a greater incidence of adverse events (specifically major stroke, bleeding, and vascular complications). We searched PubMed and Embase (2008–2017) for relevant studies. Studies with <1 year follow‐up and those not evaluating advanced CKD or outcomes post‐TAVR were excluded. Our co–primary endpoints were the incidence of short‐term mortality (defined as in‐hospital or 30‐day mortality) and long‐term mortality (1 year). Our secondary endpoints included incidence of major stroke, life‐threatening bleeding, and major vascular complications. Eleven observational studies with a total population of 10709 patients met the selection criteria. Among patients with CKD there was an increased risk of short‐ and long‐term mortality in high‐surgical‐risk patients who underwent TAVR (hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.22–1.88 and HR: 1.56, 95% CI: 1.38–1.77, respectively; P < 0.01). However, there was no association between CKD and mortality in low‐ to intermediate‐risk patients (HR: 1.35, 95% CI: 0.98–1.84, P = 0.06 in short‐term and HR: 1.08, 95% CI: 0.92–1.27, P = 0.34 in long‐term). In low‐ to intermediate‐risk TAVR patients, advanced CKD is not associated with increased mortality or poorer safety outcomes. These findings should be factored into the clinical decision‐making process regarding TAVR candidacy.     

Herpes zoster incidence in a multicenter cohort of solid organ transplant recipients

S.A. Pergam, C.W. Forsberg, M.J. Boeckh, C. Maynard, A.P. Limaye, A. Wald, N.L. Smith, B.A. Young. Herpes zoster incidence in a multicenter cohort of solid organ transplant recipients.
Transpl Infect Dis 2011: 13: 15–23. All rights reserved Background. Immunosuppressed patients are at increased risk for herpes zoster (HZ), but incidence in solid organ transplant (SOT) recipients has varied in multiple studies. To assess incidence of HZ, we examined patients who underwent SOT and received follow‐up care within the large multicenter US Department of Veteran's Affairs healthcare system. Methods. Incident cases of HZ were determined using ICD‐9 coding from administrative databases. A multivariable Cox proportional hazards model, adjusted for a priori risk factors, was used to assess demographic factors associated with development of HZ. Results. Among the 1077 eligible SOT recipients, the cohort‐specific incidence rate of HZ was 22.2 per 1000 patient‐years (95% confidence interval [CI], 18.1–27.4). African Americans (37.6 per 1000 [95% CI, 25.0–56.6]) and heart transplants recipients (40.0 per 1000 [95% CI, 23.2–68.9]) had the highest incidence of HZ. Patients transplanted between 2005 and 2007 had the lowest incidence (15.3 per 1000 [95% CI, 8.2–28.3]). In a multivariable model, African Americans (hazard ratio [HR] 1.88; 95% CI: 1.12, 3.17) and older transplant recipients (HR 1.13; 95% CI: 1.01, 1.27 [per 5‐year increment]) had increased relative hazards of HZ. Conclusions. These data demonstrate that HZ is a common infectious complication following SOT. Future studies focused on HZ prevention are needed in this high‐risk population.     

HCV reinfection incidence among individuals treated for recent infection

One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV‐positive and HIV‐negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end‐of‐treatment response in four open‐label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequencing of the Core‐E2 and/or NS5B regions. Reinfection incidence was calculated using person‐time of observation. Exact Poisson regression analysis was used to assess factors associated with HCV reinfection. The cohort at risk for reinfection (n=120; 83% male; median age 36 years) was composed of HIV‐positive men‐who‐have‐sex‐with‐men (53%) and people who inject drugs (current 49%, ever 69%). Total follow‐up time at risk was 135 person‐years (median 1.08 years, range 0.17, 2.53). Ten cases of HCV reinfection were identified, for an incidence of 7.4 per 100 py (95% CI 4.0, 13.8). Reinfection incidence was significantly higher among participants who reported injection drug use at end of or post‐treatment, irrespective of HIV status (15.5 per 100 py, 95% CI 7.8, 31.1). In adjusted analysis, factors associated with reinfection were older age (aIRR 5.3, 95% CI 1.15, 51.5, P=.042) and injection drug use at end of or post‐treatment (aIRR 7.9, 95% CI 1.6, 77.2, P=.008). High reinfection incidence following treatment for recent HCV infection in individuals with ongoing risk behaviour emphasizes the need for post‐treatment surveillance, harm reduction strategies and education in at‐risk populations.     

Body Mass Index and Survival in Men and Women Aged 70 to 75

OBJECTIVES: To examine in an older population all‐cause and cause‐specific mortality associated with underweight (body mass index (BMI)<18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), and obesity (BMI≥30.0). DESIGN: Cohort study. SETTING: The Health in Men Study and the Australian Longitudinal Study of Women's Health. PARTICIPANTS: Adults aged 70 to 75, 4,677 men and 4,563 women recruited in 1996 and followed for up to 10 years. MEASUReMENTS: Relative risk of all‐cause mortality and cause‐specific (cardiovascular disease, cancer, and chronic respiratory disease) mortality. RESULTS: Mortality risk was lowest for overweight participants. The risk of death for overweight participants was 13% less than for normal‐weight participants (hazard ratio (HR)=0.87, 95% CI=0.78–0.94). The risk of death was similar for obese and normal‐weight participants (HR=0.98, 95% CI=0.85–1.11). Being sedentary doubled the mortality risk for women across all levels of BMI (HR=2.08, 95% CI=1.79–2.41) but resulted in only a 28% greater risk for men (HR=1.28 (95% CI=1.14–1.44). CONCLUSION: These results lend further credence to claims that the BMI thresholds for overweight and obese are overly restrictive for older people. Overweight older people are not at greater mortality risk than those who are normal weight. Being sedentary was associated with a greater risk of mortality in women than in men.     

Rheumatoid arthritis and mortality. A longitudinal study in pima indians

Objective. To determine the effect of rheumatoid arthritis (RA) on mortality rates. Methods. Longitudinal analyses of data from a cohort of Pima Indians from the Gila River Indian Community in Arizona, who were followed up during the period February 1965 through December 1989. Results. Among 2,979 study subjects aged ≤25 years, there were 858 deaths, 79 of which occurred in subjects with RA (36 men, 43 women). Age and sex-adjusted mortality rates were slightly higher in subjects with RA than in those without (mortality rate ratio 1.28, 95% confidence interval [95% CI] 1.01–1.62). Among those with RA, mortality rates were higher in older subjects (mortality rate ratio 1.51 per 10-year increase in age, 95% CI 1.22–1.88), in male subjects (mortality rate ratio 2.23, 95% CI 1.44–3.45, adjusted for age), and in subjects with proteinuria (mortality rate ratio 1.88, 95% CI 1.02–3.46, adjusted for age and sex). Mortality rate ratios for these risk factors were similar in subjects without RA. In addition, among subjects with RA, rheumatoid factor (RF) positivity was predictive of death (mortality rate ratio 1.94, 95% CI 1.10–3.43), and the excess mortality was found primarily among subjects who were seropositive. The death rate from cardiovascular disease (mortality rate ratio 1.77, 95% CI 1.10–2.84) and from liver cirrhosis or other alcohol-related disease (mortality rate ratio 2.52, 95% CI 1.06–6.01) was increased in persons with RA. Conclusion. The results of this population-based study suggest that although the risk of mortality in subjects with RA is significantly higher than in those without RA, the risk ratio is in the lower range of that described previously in studies of clinic-based cohorts. RF positivity as a predictor of early death among subjects with RA indicates that the immunologic processes in seropositive RA may contribute to the events that eventually lead to early death.     

Reasons for intentional weight loss, unintentional weight loss, and mortality in older men

BACKGROUND: We have examined the relationship between intentional and unintentional weight loss and the reasons underlying intention to lose weight and all-cause mortality and mortality due to cardiovascular disease (CVD) and non-CVD causes in older men. METHODS: Prospective study of 4869 men aged 56 to 75 years drawn from general practices in 24 British towns, who in 1996 completed questionnaires about intentional and unintentional weight loss over the preceding 4 years and were followed up for a subsequent 7 years. RESULTS: Unintentional but not intentional weight loss was associated with a significant increase in risk of all-cause mortality compared with men who reported no weight change, even after adjustment for lifestyle characteristics and preexisting disease (adjusted relative risk [RR], 1.71; 95% confidence interval [CI], 1.33-2.19; and RR, 1.00; 95% CI, 0.91-1.10, respectively). Men who lost weight intentionally as a result of personal choice showed significant benefit in all-cause mortality (RR, 0.59; 95% CI, 0.34-1.00; P = .05), which was largely owing to a significant reduction in mortality from non-CVD causes (RR, 0.36; 95% CI, 0.15-0.87). The benefit in these men was most apparent in markedly overweight men (BMI [calculated as weight in kilograms divided by the square of height in meters] > or = 28) and in younger men (age < 65 years). Men who lost weight intentionally owing to ill health or physician's advice showed an increased risk of all-cause mortality (RR, 1.37; 95% CI, 0.96-1.94). No harm or benefit was seen for CVD mortality, irrespective of reasons for intentional weight loss. CONCLUSION: Intentional weight loss carried out for personal reasons is associated with a significant reduction in all-cause mortality in markedly overweight men, and the data suggest that the earlier the intervention, the greater the chance of benefit.