Objectives The aim of this study was to determine whether ectopic fat depots are prospectively associated with cardiovascular disease, cancer, and all-cause mortality. Background The morbidity ...associated with excess body weight varies among individuals of similar body mass index. Ectopic fat depots may underlie this risk differential. However, prospective studies of directly measured fat are limited. Methods Participants from the Framingham Heart Study (n = 3,086; 49% women; mean age of 50.2 years) underwent assessment of fat depots (visceral adipose tissue, pericardial adipose tissue, and periaortic adipose tissue) using multidetector computed tomography and were followed up longitudinally for a median of 5.0 years. Cox proportional hazards regression models were used to examine the association of each fat depot (per 1 SD increment) with the risk of incident cardiovascular disease, cancer, and all-cause mortality after adjustment for standard risk factors, including body mass index. Results Overall, there were 90 cardiovascular events, 141 cancer events, and 71 deaths. After multivariable adjustment, visceral adipose tissue was associated with cardiovascular disease (hazard ratio: 1.44; 95% confidence interval: 1.08 to 1.92; p = 0.01) and cancer (hazard ratio: 1.43; 95% confidence interval: 1.12 to 1.84; p = 0.005). Addition of visceral adipose tissue to a multivariable model that included body mass index modestly improved cardiovascular risk prediction (net reclassification improvement of 16.3%). None of the fat depots were associated with all-cause mortality. Conclusions Visceral adiposity is associated with incident cardiovascular disease and cancer after adjustment for clinical risk factors and generalized adiposity. These findings support the growing appreciation of a pathogenic role of ectopic fat.
AbstractObjectiveTo evaluate the association between physical distancing interventions and incidence of coronavirus disease 2019 (covid-19) globally.DesignNatural experiment using interrupted time ...series analysis, with results synthesised using meta-analysis.Setting149 countries or regions, with data on daily reported cases of covid-19 from the European Centre for Disease Prevention and Control and data on the physical distancing policies from the Oxford covid-19 Government Response Tracker.ParticipantsIndividual countries or regions that implemented one of the five physical distancing interventions (closures of schools, workplaces, and public transport, restrictions on mass gatherings and public events, and restrictions on movement (lockdowns)) between 1 January and 30 May 2020.Main outcome measureIncidence rate ratios (IRRs) of covid-19 before and after implementation of physical distancing interventions, estimated using data to 30 May 2020 or 30 days post-intervention, whichever occurred first. IRRs were synthesised across countries using random effects meta-analysis.ResultsOn average, implementation of any physical distancing intervention was associated with an overall reduction in covid-19 incidence of 13% (IRR 0.87, 95% confidence interval 0.85 to 0.89; n=149 countries). Closure of public transport was not associated with any additional reduction in covid-19 incidence when the other four physical distancing interventions were in place (pooled IRR with and without public transport closure was 0.85, 0.82 to 0.88; n=72, and 0.87, 0.84 to 0.91; n=32, respectively). Data from 11 countries also suggested similar overall effectiveness (pooled IRR 0.85, 0.81 to 0.89) when school closures, workplace closures, and restrictions on mass gatherings were in place. In terms of sequence of interventions, earlier implementation of lockdown was associated with a larger reduction in covid-19 incidence (pooled IRR 0.86, 0.84 to 0.89; n=105) compared with a delayed implementation of lockdown after other physical distancing interventions were in place (pooled IRR 0.90, 0.87 to 0.94; n=41).ConclusionsPhysical distancing interventions were associated with reductions in the incidence of covid-19 globally. No evidence was found of an additional effect of public transport closure when the other four physical distancing measures were in place. Earlier implementation of lockdown was associated with a larger reduction in the incidence of covid-19. These findings might support policy decisions as countries prepare to impose or lift physical distancing measures in current or future epidemic waves.
Objectives This study sought to evaluate 4-year outcomes of percutaneous repair versus surgery for mitral regurgitation. Background Transcatheter therapies are being developed to treat valvular heart ...disease. In the EVEREST (Endovascular Valve Edge-to-Edge Repair Study) II trial, treatment of mitral valve regurgitation (MR) with a novel percutaneous device was compared with surgery and showed superior safety, but less reduction in MR at 1 year overall. We report the 4-year outcomes from the EVEREST II trial. Methods Patients with grade 3+ or 4+ MR were randomly assigned to percutaneous repair with the MitraClip (Abbott, Menlo Park, California) device or conventional mitral valve surgery in a 2:1 ratio (184:95). Patients prospectively consented to 5 years of follow-up. Results At 4 years, the rate of the composite endpoint of freedom from death, surgery, or 3+ or 4+ MR in the intention-to-treat population was 39.8% versus 53.4% in the percutaneous repair group and surgical groups, respectively (p = 0.070). Rates of death were 17.4% versus 17.8% (p = 0.914), and 3+ or 4+ MR was present in 21.7% versus 24.7% (p = 0.745) at 4 years of follow-up, respectively. Surgery for mitral valve dysfunction, however, occurred in 20.4% versus 2.2% (p < 0.001) at 1 year and 24.8% versus 5.5% (p < 0.001) at 4 years. Conclusions Patients treated with percutaneous repair of the mitral valve more commonly required surgery to treat residual MR; however, after the first year of follow-up, there were few surgeries required after either percutaneous or surgical treatment and no difference in the prevalence of moderate-severe and severe MR or mortality at 4 years. (Endovascular Valve Edge-to-Edge Repair Study EVEREST II; NCT00209274 )
BACKGROUND—Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) vary in volume and quality. We evaluated whether fat volume or attenuation (indirect measure of quality) predicts ...metabolic risk factor changes.
METHODS AND RESULTS—Framingham Heart Study Multi-detector Computed Tomography Substudy participants (n=1730, 45% women) were followed up over a mean of 6.2 years. Baseline VAT and SAT volume (in cm) and attenuation (in Hounsfield units) were assessed. Outcomes included blood pressure, lipids, and glucose. We constructed multivariable regression models predicting change from baseline to follow-up. Baseline VAT was associated with metabolic risk factors at follow-up. Per 500-cm increase in baseline VAT, glucose was 2.34 mg/dL higher (95% confidence interval, 1.71–2.97) and high-density lipoprotein was 1.62 mg/dL lower (95% confidence interval, 0.97–2.28) in women (P<0.0001 for both). These findings remained significant after adjustment for body mass index. Results for SAT were similar although less striking. Lower (more negative) fat attenuation was associated with more adverse metabolic profiles at follow-up. For example, per 5-unit decrease in baseline VAT Hounsfield units, log triglycerides increased by 0.08 mg/dL (95% confidence interval, 0.05–0.12; P=0.005), which remained significant after adjustment for baseline VAT. Among men, VAT and SAT Hounsfield units were associated with changes in cardiovascular disease risk factors but were mostly attenuated after baseline volume adjustment.
CONCLUSIONS—VAT volume and SAT volume are associated with incident metabolic risk factors beyond overall adiposity. Decreases in fat attenuation are also associated with incident risk factors. These findings suggest that both volume and quality of VAT and SAT contribute to metabolic risk.
IMPORTANCE: Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding. OBJECTIVE: To develop a clinical decision tool to identify patients ...expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI. DESIGN, SETTING, AND PARTICIPANTS: Among 11 648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014). EXPOSURES: Twelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin. MAIN OUTCOMES AND MEASURES: Ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI. RESULTS: Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; −1 point for age 65 to younger than 75 years; and −2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference RD, −3.0% 95% CI, −4.1% to −2.0%, P < .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, −0.7% 95% CI, −1.4% to 0.09%, P = .07; interaction P < .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% 95% CI, −0.3% to 1.0%, P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% 95% CI, 0.8% to 2.3%, P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding. CONCLUSION AND RELEVANCE: Among patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00977938.
In this trial, 947 patients with renal-artery stenosis were assigned to renal-artery stenting or medical therapy. At a median of 43 months, there was no significant between-group difference in the ...rate of a composite end point of adverse cardiovascular and renal events.
Renal-artery stenosis, which is present in 1 to 5% of people with hypertension,
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often occurs in combination with peripheral arterial or coronary artery disease.
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Results of community-based screening suggest that the prevalence among persons older than 65 years of age may be as high as 7%.
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Renal-artery stenosis may result in hypertension, ischemic nephropathy, and multiple long-term complications.
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Uncontrolled studies performed in the 1990s suggested that renal-artery angioplasty or stenting resulted in significant reductions in systolic blood pressure
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and in the stabilization of chronic kidney disease.
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Subsequently, there were rapid increases in the rate of renal-artery . . .
Summary Background Atrial fibrillation contributes to substantial increases in morbidity and mortality. We aimed to develop a risk score to predict individuals' absolute risk of developing the ...condition, and to provide a framework for researchers to assess new risk markers. Methods We assessed 4764 participants in the Framingham Heart Study from 8044 examinations (55% women, 45–95 years of age) undertaken between June, 1968, and September, 1987. Thereafter, participants were monitored for the first event of atrial fibrillation for a maximum of 10 years. Multivariable Cox regression identified clinical risk factors associated with development of atrial fibrillation in 10 years. Secondary analyses incorporated routine echocardiographic measurements (5152 participants, 7156 examinations) to reclassify the risk of atrial fibrillation and to assess whether these measurements improved risk prediction. Findings 457 (10%) of the 4764 participants developed atrial fibrillation. Age, sex, body-mass index, systolic blood pressure, treatment for hypertension, PR interval, clinically significant cardiac murmur, and heart failure were associated with atrial fibrillation and incorporated in a risk score (p<0·05, except body-mass index p=0·08), clinical model C statistic 0·78 (95% CI 0·76–0·80). Risk of atrial fibrillation in 10 years varied with age: more than 15% risk was recorded in 53 (1%) participants younger than 65 years, compared with 783 (27%) older than 65 years. Additional incorporation of echocardiographic measurements to enhance the risk prediction model only slightly improved the C statistic from 0·78 (95% CI 0·75–0·80) to 0·79 (0·77–0·82), p=0·005. Echocardiographic measurements did not improve risk reclassification (p=0·18). Interpretation From clinical factors readily accessible in primary care, our risk score could help to identify risk of atrial fibrillation for individuals in the community, assess technologies or markers for improvement of risk prediction, and target high-risk individuals for preventive measures. Funding US National Institutes of Health.
Abstract Background Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are associated with adverse cardiometabolic risk profiles. Objectives This study explored the degree to which ...changes in abdominal fat quantity and quality are associated with changes in cardiovascular disease (CVD) risk factors. Methods Study participants (n = 1,106; 44.1% women; mean baseline age 45.1 years) were drawn from the Framingham Heart Study Third Generation cohort who participated in the computed tomography (CT) substudy Exams 1 and 2. Participants were followed for 6.1 years on average. Abdominal adipose tissue volume in cm3 and attenuation in Hounsfield units (HU) were determined by CT-acquired abdominal scans. Results The mean fat volume change was an increase of 602 cm3 for SAT and an increase of 703 cm3 for VAT; the mean fat attenuation change was a decrease of 5.5 HU for SAT and an increase of 0.07 HU for VAT. An increase in fat volume and decrease in fat attenuation were associated with adverse changes in CVD risk factors. An additional 500 cm3 increase in fat volume was associated with incident hypertension (odds ratio OR: 1.21 for SAT; OR: 1.30 for VAT), hypertriglyceridemia (OR: 1.15 for SAT; OR: 1.56 for VAT), and metabolic syndrome (OR: 1.43 for SAT; OR: 1.82 for VAT; all p < 0.05). Similar trends were observed for each additional 5 HU decrease in abdominal adipose tissue attenuation. Most associations remained significant even after further accounting for body mass index change, waist circumference change, or respective abdominal adipose tissue volumes. Conclusions Increasing accumulation of fat quantity and decreasing fat attenuation are associated with worsening of CVD risk factors beyond the associations with generalized adiposity, central adiposity, or respective adipose tissue volumes.
Current screening and detection of asymptomatic aortic aneurysms is based largely on uniform cut-point diameters. The aims of this study were to define normal aortic diameters in asymptomatic men and ...women in a community-based cohort and to determine the association between aortic diameters and traditional risk factors for cardiovascular disease. Measurements of the diameters of the ascending thoracic aorta (AA), descending thoracic aorta (DTA), infrarenal abdominal aorta (IRA), and lower abdominal aorta (LAA) were acquired from 3,431 Framingham Heart Study (FHS) participants. Mean diameters were stratified by gender, age, and body surface area. Univariate associations with risk factor levels were examined, and multivariate linear regression analysis was used to assess the significance of covariate-adjusted relations with aortic diameters. For men, the average diameters were 34.1 mm for the AA, 25.8 mm for the DTA, 19.3 mm for the IRA, and 18.7 mm for the LAA. For women, the average diameters were 31.9 mm for the AA, 23.1 mm for the DTA, 16.7 mm for the IRA, and 16.0 mm for the LAA. The mean aortic diameters were strongly correlated (p <0.0001) with age and body surface area in age-adjusted analyses, and these relations remained significant in multivariate regression analyses. Positive associations of diastolic blood pressure with AA and DTA diameters in both genders and pack-years of cigarette smoking with DTA diameter in women and IRA diameter in men and women were observed. In conclusion, average diameters of the thoracic and abdominal aorta by computed tomography are larger in men compared with women, vary significantly with age and body surface area, and are associated with modifiable cardiovascular disease risk factors, including diastolic blood pressure and cigarette smoking.
Abstract Background The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations. ...Objectives This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI. Methods The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding. Results Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21). Conclusions Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study The DAPT Study; NCT00977938 )
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