[Show abstract][Hide abstract] ABSTRACT: Autologous pericardium annuloplasty (APA) is an alternative to prosthetic ring implantation for mitral valve (MV) repair, avoiding the use of foreign material and preserving the mitral annulus' physiological motion. However, data on durability are questionable. Therefore, we analyzed long-term outcomes of treating degenerative mitral regurgitation (MR) with APA.
[Show abstract][Hide abstract] ABSTRACT: Background
Ageing populations may demand more blood transfusions, but the blood supply could be limited by difficulties in attracting and retaining a decreasing pool of younger donors. One approach to increase blood supply is to collect blood more frequently from existing donors. If more donations could be safely collected in this manner at marginal cost, then it would be of considerable benefit to blood services. National Health Service (NHS) Blood and Transplant in England currently allows men to donate up to every 12 weeks and women to donate up to every 16 weeks. In contrast, some other European countries allow donations as frequently as every 8 weeks for men and every 10 weeks for women. The primary aim of the INTERVAL trial is to determine whether donation intervals can be safely and acceptably decreased to optimise blood supply whilst maintaining the health of donors.
INTERVAL is a randomised trial of whole blood donors enrolled from all 25 static centres of NHS Blood and Transplant. Recruitment of about 50,000 male and female donors started in June 2012 and was completed in June 2014. Men have been randomly assigned to standard 12-week versus 10-week versus 8-week inter-donation intervals, while women have been assigned to standard 16-week versus 14-week versus 12-week inter-donation intervals. Sex-specific comparisons will be made by intention-to-treat analysis of outcomes assessed after two years of intervention. The primary outcome is the number of blood donations made. A key secondary outcome is donor quality of life, assessed using the Short Form Health Survey. Additional secondary endpoints include the number of 'deferrals' due to low haemoglobin (and other factors), iron status, cognitive function, physical activity, and donor attitudes. A comprehensive health economic analysis will be undertaken.
The INTERVAL trial should yield novel information about the effect of inter-donation intervals on blood supply, acceptability, and donors' physical and mental well-being. The study will generate scientific evidence to help formulate blood collection policies in England and elsewhere.
[Show abstract][Hide abstract] ABSTRACT: To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score.METHODS: Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of ≤6 points, n = 677). We tested 15 clinical, 5 radiologic, and 3 echocardiographic variables for associations with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant.RESULTS: Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA. For all other predictors, effects were significantly different in the 2 RoPE score categories. For the low RoPE score group, but not the high RoPE score group, older age and antiplatelet (vs warfarin) treatment predicted recurrence. Conversely, echocardiographic features (septal hypermobility and a small shunt) and a prior (clinical) stroke/TIA were significant predictors in the high but not low RoPE score group.CONCLUSION: Predictors of recurrence differ when PFO relatedness is classified by the RoPE score, suggesting that patients with CS and PFO form a heterogeneous group with different stroke mechanisms. Echocardiographic features were only associated with recurrence in the high RoPE score group.
[Show abstract][Hide abstract] ABSTRACT: The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain.
To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk.
Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment.
Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥7.5%) risk.
During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels.
In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.
JAMA The Journal of the American Medical Association 03/2014; 311(12):1225-33. · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Guidelines advocate changes in fatty acid consumption to promote cardiovascular health.
To summarize evidence about associations between fatty acids and coronary disease.
MEDLINE, Science Citation Index, and Cochrane Central Register of Controlled Trials through July 2013.
Prospective, observational studies and randomized, controlled trials.
Investigators extracted data about study characteristics and assessed study biases.
There were 32 observational studies (530 525 participants) of fatty acids from dietary intake; 17 observational studies (25 721 participants) of fatty acid biomarkers; and 27 randomized, controlled trials (103 052 participants) of fatty acid supplementation. In observational studies, relative risks for coronary disease were 1.02 (95% CI, 0.97 to 1.07) for saturated, 0.99 (CI, 0.89 to 1.09) for monounsaturated, 0.93 (CI, 0.84 to 1.02) for long-chain ω-3 polyunsaturated, 1.01 (CI, 0.96 to 1.07) for ω-6 polyunsaturated, and 1.16 (CI, 1.06 to 1.27) for trans fatty acids when the top and bottom thirds of baseline dietary fatty acid intake were compared. Corresponding estimates for circulating fatty acids were 1.06 (CI, 0.86 to 1.30), 1.06 (CI, 0.97 to 1.17), 0.84 (CI, 0.63 to 1.11), 0.94 (CI, 0.84 to 1.06), and 1.05 (CI, 0.76 to 1.44), respectively. There was heterogeneity of the associations among individual circulating fatty acids and coronary disease. In randomized, controlled trials, relative risks for coronary disease were 0.97 (CI, 0.69 to 1.36) for α-linolenic, 0.94 (CI, 0.86 to 1.03) for long-chain ω-3 polyunsaturated, and 0.89 (CI, 0.71 to 1.12) for ω-6 polyunsaturated fatty acid supplementations.
Potential biases from preferential publication and selective reporting.
Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.
British Heart Foundation, Medical Research Council, Cambridge National Institute for Health Research Biomedical Research Centre, and Gates Cambridge.
Annals of internal medicine 03/2014; 160(6). · 13.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A region-specific (urban and rural parts of north, east, west, and south India) systematic review and meta-analysis of the prevalence, awareness, and control of hypertension among Indian patients have not been done before.
Medline, Web of Science, and Scopus databases from 1950 to 30 April 2013 were searched for 'prevalence, burden, awareness, and control of blood pressure (BP) or hypertension (≥140 SBP and or ≥90 DBP) among Indian adults' (≥18 years). Of the total 3047 articles, 142 were included.
Overall prevalence for hypertension in India was 29.8% (95% confidence interval: 26.7-33.0). Significant differences in hypertension prevalence were noted between rural and urban parts [27.6% (23.2-32.0) and 33.8% (29.7-37.8); P = 0.05]. Regional estimates for the prevalence of hypertension were as follows: 14.5% (13.3-15.7), 31.7% (30.2-33.3), 18.1% (16.9-19.2), and 21.1% (20.1-22.0) for rural north, east, west, and south India; and 28.8% (26.9-30.8), 34.5% (32.6-36.5), 35.8% (35.2-36.5), and 31.8% (30.4-33.1) for urban north, east, west, and south India, respectively. Overall estimates for the prevalence of awareness, treatment, and control of BP were 25.3% (21.4-29.3), 25.1% (17.0-33.1), and 10.7% (6.5-15.0) for rural Indians; and 42.0% (35.2-48.9), 37.6% (24.0-51.2), and 20.2% (11.6-28.7) for urban Indians.
About 33% urban and 25% rural Indians are hypertensive. Of these, 25% rural and 42% urban Indians are aware of their hypertensive status. Only 25% rural and 38% of urban Indians are being treated for hypertension. One-tenth of rural and one-fifth of urban Indian hypertensive population have their BP under control.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
Journal of Hypertension 03/2014; · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the prognostic utility of isolated T-wave inversion (TWI), QRS duration, and QRS/T angle on electrocardiogram at rest as predictors for sudden cardiac death (SCD) and death from all causes. The assessment of electrocardiographic findings was based on a population-based cohort of 1,951 men (age 42 to 61 years) with a follow-up period of 20 years. Isolated TWI in the absence of ST depression, bundle branch block or major arrhythmias, prolonged QRS duration from 110 to 119 ms, and a wide QRS/T angle of >67° were identified from the 12-lead electrocardiograms. SCD was observed in 171 men (8.3%) during the follow-up. As a single electrocardiographic parameter, TWI (prevalence 2.4%) was associated with an increased risk of SCD (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.91 to 5.71, p <0.001) after adjustment for age and clinical factors. Similarly, prolonged QRS duration and wide QRS/T angle were significantly related to the risk of SCD, with HR 1.50 (95% CI 1.08 to 2.19, p = 0.017) for QRS duration and HR 3.03 (95% CI 2.23 to 4.14, p <0.001) for QRS/T angle. The integrated discrimination improvement was significant when TWI (0.014, p = 0.036) or QRS/T angle (0.015, p = 0.002) was added to the model with age and clinical factors. In conclusion, TWI, QRS duration, and QRS/T angle are significantly associated with the risk of SCD and death from all causes beyond conventional cardiovascular risk predictors in the general population.
The American journal of cardiology 01/2014; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS), though the pathogenicity of a discovered PFO in the setting of CS is typically unclear. Transesophageal echocardiography (TEE) features such as PFO size, an associated hypermobile septum, and presence of a right-to-left shunt at rest have all been proposed as markers of risk. The association of these TEE features with other markers of pathogenicity has not been examined.
-We used a recently derived score based on clinical and neuroimaging features to stratify patients with PFO and CS by the probability that their stroke is PFO-attributable. We examined whether high risk TEE features are seen more frequently in patients more likely to have had a PFO-attributable stroke (n = 637) compared to those less likely to have a PFO attributable stroke (n = 657). Large physiologic shunt size was not more frequently seen among those with probable PFO-attributable strokes (OR=0.92; p = 0.53). Neither the presence of a hypermobile septum nor a right-to-left shunt at rest were detected more often in those with a probable PFO-attributable stroke (OR=0.80; p = 0.45 and OR=1.15; 0.11 respectively).
-We found no evidence that the proposed TEE risk markers of large PFO size, hypermobile septum, and presence of right-to-left shunt at rest are associated with clinical features suggesting that a CS is PFO-attributable. Additional tools to describe PFOs may be useful in helping to determine whether an observed PFO is incidental or pathogenically related to CS.
[Show abstract][Hide abstract] ABSTRACT: Risk profiles for stroke recurrence are poorly characterized.
We determined the variation in the risk and type of recurrent stroke among index ischemic stroke subtypes, and whether index stroke subtype and conventional stroke risk factors were predictors of stroke recurrence.
Patients enrolled in the Prevention Regimen for Effectively Avoiding Second Strokes trial were included in this study.
In 1794 patients' recurrent stroke subtypes were the same as the index stroke in: 48·3% of patients with large artery atherothrombosis stroke; 50% of patients with cardioembolic stroke; 48·7% of patients with small artery occlusion stroke; 8·1% of patients with stroke of other etiology, and 45·3% of patients with undetermined etiology stroke. Patients with cardioembolic stroke, who were unwilling or unable to take oral anticoagulants, had the greatest risk of stroke recurrence. Predictors of stroke recurrence in multivariable analysis were: older age and previous stroke among large artery atherothrombosis strokes; older age, male sex, previous stroke, previous transient ischemic attack, hypertension, diabetes, and tobacco use among small artery occlusion strokes; older age among cardioembolic strokes; atrial fibrillation and anti-diabetic medications among other etiology strokes; older age, previous stroke and atrial fibrillation among undetermined etiology strokes. Predictors of brain hemorrhage as recurrent stroke were index small artery occlusion stroke, older age, previous stroke, and antiplatelet treatment with aspirin plus extended-release dipyridamole.
Risk predictors for stroke recurrence and for brain hemorrhage differ by index ischemic stroke subtype, information that is important when initiating secondary prevention therapy.
International Journal of Stroke 10/2013; · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta-analysis of prospective studies.
Interleukin-6 (IL-6), IL-18, matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and tumour necrosis factor-α (TNF-α) were measured at baseline in a case-cohort study of 1514 participants and 833 incident CHD events within population-based prospective cohorts at the Danish Research Centre for Prevention and Health. Age- and sex-adjusted hazard ratios (HRs) for CHD per 1-SD higher log-transformed baseline levels were: 1.37 (95% CI: 1.21-1.54) for IL-6, 1.26 (1.11-1.44) for IL-18, 1.30 (1.16-1.46) for MMP-9, 1.01 (0.89-1.15) for sCD40L, and 1.13 (1.01-1.27) for TNF-α. Multivariable adjustment for conventional vascular risk factors attenuated the HRs to: 1.26 (1.08-1.46) for IL-6, 1.12 (0.95-1.31) for IL-18, 1.21 (1.05-1.39) for MMP-9, 0.93 (0.78-1.11) for sCD40L, and 1.14 (1.00-1.31) for TNF-α. In meta-analysis of up to 29 population-based prospective studies, adjusted relative risks for non-fatal MI or CHD death per 1-SD higher levels were: 1.25 (1.19-1.32) for IL-6; 1.13 (1.05-1.20) for IL-18; 1.07 (0.97-1.19) for MMP-9; 1.07 (0.95-1.21) for sCD40L; and 1.17 (1.09-1.25) for TNF-α.
Several different pro-inflammatory cytokines are each associated with CHD risk independent of conventional risk factors and in an approximately log-linear manner. The findings lend support to the inflammation hypothesis in vascular disease, but further studies are needed to assess causality.
European Heart Journal 09/2013; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO.
Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates.
Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest.
Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.
[Show abstract][Hide abstract] ABSTRACT: The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not available.
We reviewed large cohort pooling projects, evaluating effects of baseline or usual exposure to metabolic risks on ischemic heart disease (IHD), hypertensive heart disease (HHD), stroke, diabetes, and, as relevant selected other CVDs, after adjusting for important confounders. We pooled all data to estimate relative risks (RRs) for each risk factor and examined effect modification by age or other factors, using random effects models.
Across all risk factors, an average of 123 cohorts provided data on 1.4 million individuals and 52,000 CVD events. Each metabolic risk factor was robustly related to CVD. At the baseline age of 55-64 years, the RR for 10 mmHg higher SBP was largest for HHD (2.16; 95% CI 2.09-2.24), followed by effects on both stroke subtypes (1.66; 1.39-1.98 for hemorrhagic stroke and 1.63; 1.57-1.69 for ischemic stroke). In the same age group, RRs for 1 mmol/L higher TC were 1.44 (1.29-1.61) for IHD and 1.20 (1.15-1.25) for ischemic stroke. The RRs for 5 kg/m(2) higher BMI for ages 55-64 ranged from 2.32 (2.04-2.63) for diabetes, to 1.44 (1.40-1.48) for IHD. For 1 mmol/L higher FPG, RRs in this age group were 1.18 (1.08-1.29) for IHD and 1.14 (1.01-1.29) for total stroke. For all risk factors, proportional effects declined with age, were generally consistent by sex, and differed by region in only a few age groups for certain risk factor-disease pairs.
Our results provide robust, comparable and precise estimates of the effects of major metabolic risk factors on CVD and diabetes by age group.
PLoS ONE 07/2013; 8(7):65174-. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease.
We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis.
One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P=9.0×10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P=1.5×10(-8) and P=1.8×10(-8), respectively), but the findings were not replicated consistently.
Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.).
New England Journal of Medicine 02/2013; 368(6):503-12. · 54.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) and cryptogenic stroke are commonly associated but some PFOs are incidental. Specific radiological findings associated with PFO may be more likely to indicate a PFO-related cause. We examined whether specific radiological findings are associated with PFO among subjects with cryptogenic stroke and known PFO status. METHODS: We analyzed the Risk of Paradoxical Embolism(RoPE) Study database of subjects with cryptogenic stroke and known PFO status, for associations between PFO and: (1) index stroke seen on imaging, (2) index stroke size, (3) index stroke location, (4) multiple index strokes, and (5) prior stroke on baseline imaging. We also compared imaging with purported high-risk echocardiographic features. RESULTS: Subjects (N=2680) were significantly more likely to have a PFO if their index stroke was large (odds ratio [OR], 1.36; P=0.0025), seen on index imaging (OR, 1.53; P=0.003), and superficially located (OR, 1.54; P<0.0001). A prior stroke on baseline imaging was associated with not having a PFO (OR, 0.66; P<0.0001). Finding multiple index strokes was unrelated to PFO status (OR, 1.21; P=0.161). No echocardiographic variables were related to PFO status. CONCLUSIONS: This is the largest study to report the radiological characteristics of patients with cryptogenic stroke and known PFO status. Strokes that were large, radiologically apparent, superficially located, or unassociated with prior radiological infarcts were more likely to be PFO-associated than were unapparent, smaller, or deep strokes, and those accompanied by chronic infarcts. There was no association between PFO and multiple acute strokes nor between specific echocardiographic PFO features with neuroimaging findings.