Interaction between cardiovascular risk factors and body mass index and 10-year incidence of cardiovascular disease, cancer death, and overall mortality.

The effect of above-normal body mass index (BMI) on health outcomes is controversial because it is difficult to distinguish from the effect due to BMI-associated cardiovascular risk factors. The objective was to analyze the impact on 10-year incidence of cardiovascular disease, cancer deaths and overall mortality of the interaction between cardiovascular risk factors and BMI. We conducted a pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79years old at basal examination. Body mass index was measured at baseline being the outcome measures ten-year cardiovascular disease, cancer and overall mortality. Multivariable analyses were adjusted for potential confounders, considering the significant interactions with cardiovascular risk factors. We included 54,446 individuals (46.5% with overweight and 27.8% with obesity). After considering the significant interactions, the 10-year risk of cardiovascular disease was significantly increased in women with overweight and obesity [Hazard Ratio=2.34 (95% confidence interval: 1.19-4.61) and 5.65 (1.54-20.73), respectively]. Overweight and obesity significantly increased the risk of cancer death in women [3.98 (1.53-10.37) and 11.61 (1.93-69.72)]. Finally, obese men had an increased risk of cancer death and overall mortality [1.62 (1.03-2.54) and 1.34 (1.01-1.76), respectively]. In conclusion, overweight and obesity significantly increased the risk of cancer death and of fatal and non-fatal cardiovascular disease in women; whereas obese men had a significantly higher risk of death for all causes and for cancer. Cardiovascular risk factors may act as effect modifiers in these associations.

Epicardial Adipose Tissue in the General Middle-aged Population and Its Association With Metabolic Syndrome.

INTRODUCTION AND OBJECTIVES: There is currently increasing interest in epicardial adipose tissue (EAT) as a marker of cardiovascular disease. Our purpose was to describe EAT, measured by transthoracic echocardiography, and to assess its association with metabolic syndrome (MS) in the RIVANA population-based study. METHODS: Physical examination was performed in 880 participants aged 45 to 74 years (492 of them with MS according to the harmonized definition). Fasting glucose, high-density lipoprotein cholesterol, triglyceride, and C-reactive protein concentrations were determined in a blood sample. In all participants, EAT thickness was measured with transthoracic echocardiography at end-systole. RESULTS: Among participants without MS, the prevalence of EAT ≥ 5mm significantly increased with age (OR > 65 years vs 45-54 years=8.22; 95%CI, 3.90-17.35; P for trend<.001). Increasing EAT quintiles were significantly associated with MS (OR fifth quintile vs first quintile=3.26; 95%CI, 1.59-6.71; P for trend=.001). Considering the different MS criteria, increasing quintiles of EAT were independently associated with low high-density lipoprotein cholesterol (OR fifth quintile vs first quintile=2.65; 95%CI, 1.16-6.05; P for trend=.028), high triglycerides (OR fifth quintile vs first quintile=2.22; 95%CI, 1.26-3.90; P for trend=.003), and elevated waist circumference (OR fifth quintile vs first quintile=6.85; 95%CI, 2.91-16.11; P for trend<.001). CONCLUSIONS: In a subsample of the general population, EAT measured by echocardiography increased significantly and independently with age. Increased EAT thickness was independently associated with MS and with low high-density lipoprotein cholesterol, high triglycerides, and elevated waist circumference as individual criteria.

Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks Analysis.

OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS: We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.

Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.

OBJECTIVES: This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis. BACKGROUND: Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated. METHODS: We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism. RESULTS: Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy. CONCLUSIONS: The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.

Antithrombotic therapy in elderly patients with atrial fibrillation: effects and bleeding complications: a stratified analysis of the NASPEAF randomized trial.

AIMS: Atrial fibrillation patients with prior embolism have a high risk of vascular events in spite of anticoagulant therapy and elderly patients carry an additional risk. We analysed and compared vascular events-rate between older and younger than 75 years atrial fibrillation patients randomized to anticoagulant-alone or combined antiplatelet plus moderate-level anticoagulant therapy. METHODS AND RESULTS: A total of 967 patients stratified by age and the history of prior embolism were randomized to therapeutic doses of anticoagulant-alone or combined antithrombotic therapy. Primary events were fatal and non-fatal ischaemic or haemorrhagic stroke/transient ischaemic attack, systemic embolism and myocardial infarction, sudden death and death from bleeding. The elderly, compared with the younger patients, had higher event-rate [hazard ratio 2.31 (95% confidence interval 1.37-3.90), P < 0.003]. The elderly suffered higher severe bleeding event-rate during anticoagulant therapy. The combined, compared with the anticoagulant therapy, reduced the vascular events-rate in the elderly (P = 0.012) and caused less intracranial haemorrhages and less bleeding mortality, although more non-fatal gastric bleeding. CONCLUSION: The elderly with AF had a higher event-rate than the younger patients. A higher severe bleeding event-rate was also registered in elderly patients receiving anticoagulant therapy. Combined, compared with anticoagulant therapy, significantly reduced vascular events and bleeding mortality in elderly patients.

Effect of antithrombotic therapy in patients with mitral stenosis and atrial fibrillation: a sub-analysis of NASPEAF randomized trial.

AIMS: The randomized NASPEAF study included non-valvular with prior embolism and mitral stenosis patients in the same group. This is a sub-study to specially focus on the antithrombotic therapy in mitral stenosis. METHODS AND RESULTS: We analysed 311 patients with mitral stenosis, compared with 175 non-valvular atrial fibrillation patients with prior embolism, stratified by a history of previous embolism and assigned to anticoagulant therapy [target international normalized ratio (INR) = 2.0-3.0] or combined antiplatelet plus moderate intensity anticoagulant therapy. Median follow-up was 2.9 years. Outcomes were fatal and non-fatal embolism, stroke and myocardial infarction, sudden death, and death from bleeding. Combined therapy in mitral stenosis patients, compared with anticoagulant alone therapy, reduced the risk of vascular events by 58.3%. During equal therapy, the outcome annual rates were essentially the same in non-valvular and valvular patients [hazard ratio 0.90 (95% confidence interval 0.37-2.16), P = 0.81]. During anticoagulant alone therapy, the annual event rate in mitral stenosis patients without prior embolism was low (2.5%) and it was very high in patients with prior embolism (6.6%). CONCLUSION: Combined therapy was effective in mitral stenosis patients. Prior embolism patients are not efficiently protected with anticoagulant alone therapy for an INR of 2.0-3.0.

The Medtronic Intact bioprosthesis: clinical and hemodynamic performance over 13 years.

We evaluated our results over 13 years with the aortic-position Medtronic Intact bioprosthesis. Our study involved 91 consecutive patients with isolated aortic valve replacement with the Medtronic Intact bioprosthesis. The follow-up was complete for 95%. Mean follow-up was 6.61 years (range 16 days-13 years), 590 patient years. Early mortality rate was 3.3%. Late mortality was 23 patients. Survival at 13 years was 53.52% (SD = 7.63%). The linearized rate of major thromboembolism was 0.34% per patient year; rate of major bleeding events was 0.33% per patient year. The rate of nonstructural dysfunction was 0.16% per patient year. Rate of reoperation was 0.53% and rate of structural valve deterioration was 0.16% per patient year. New York Heart Association (NYHA) postoperative classes were I to II in 92.21%. Gradients were as follows: 21 to 23.87 mm Hg, 23 to 18 mm Hg, 25 to 15.5 mm Hg, and 27 to 16.50 mm Hg. Structural valve deterioration was low during the 13 years of follow-up. Valve gradients and areas remained the same over the follow-up period. The Medtronic Intact bioprosthesis shows excellent clinical and hemodynamic performance at 13 years of follow up.