Low fasting plasma insulin is associated with atrial fibrillation in men from a cohort study - the Malmö preventive project

Background: Type 2 diabetes has been associated with increased incidence of atrial fibrillation (AF) and cardiovascular disease. Controversy remains regarding the role of insulin in the epidemiology of AF risk. The aim of the present study was to study the association between fasting plasma insulin (FPI) and incidence of AF, as well as any effect modification by fasting blood glucose (FBG) or 2 h post-load blood glucose and body mass index (BMI). Methods: The study population consisted of 6052 men and 1014 women followed for an average of 26.2 years. There were 983 cases of incident AF. Analysis was performed using Cox regression and competing risks regression approaches. The population was analysed as a whole, and by subgroups according to glucose levels and BMI. Results: After adjustment for age, height, weight, systolic blood pressure and smoking there was a significant inverse association between FPI and AF (hazard ratio; HR) for 4th vs. 1st quartile: 0.69 (95% confidence interval (CI): 0.57-0.83, p < 0.0001) in the cohort as a whole. Among men the corresponding values were HR 0.64 (95% CI 0.52-0.78, p < 0.001) and among women HR 1.16 (95% CI 0.69-1.93, p = 0.58); p-value for interaction 0.06. The protective effects of insulin tended to be weaker in subjects with elevated fasting glucose, implying that the relation between FPI and incident AF could be dependent on the status of individual's glucose metabolism. Conclusions: High levels of FPI are associated with lower risk of incident AF in a middle-aged population with a long follow-up

Midlife risk factor exposure and incidence of cardiac arrest depending on cardiac or non-cardiac origin

Objective: Little is known about midlife risk factors of future cardiac arrest. Our objective was to evaluate cardiovascular risk factors in midlife in relation to the risk of cardiac arrest (CA) of cardiac and non-cardiac origin later in life. Methods: We cross-matched individuals of the population based Malmö Diet and Cancer study (n = 30,447) with the local CA registry of the city of Malmö. Baseline exposures were related to incident CA. Results: During a mean follow-up of 17.6. ±. 4.6. years, 378 CA occurred, of whom 17.2% survived to discharge. Independent midlife risk factors for CA of cardiac origin included coronary artery disease (HR 2.84 (1.86-4.34) (p 30kg/m2) (HR 2.37 (1.51-3.71) (p <0.001)), smoking (HR 2.05 (1.33-3.15) (p <0.001)) and being on antihypertensive treatment (HR 2.25 (1.46-3.46) (p <0.001)). Conclusion: Apart from smoking, which increases the risk of CA in general, the midlife risk factor pattern differs between CA of cardiac and non-cardiac origin. Whereas CA of cardiac origin is predicted by history of cardiovascular disease, dyslipidemia and diabetes mellitus, the main risk factors for CA of non-cardiac origin are obesity and hypertension. In addition to control of classical cardiovascular risk factors for prevention of CA, our results suggest that prevention of midlife obesity may reduce the risk of CA of non-cardiac origin

Angiotensin converting enzyme inhibition and aspirin in congestive heart failure

Angiotensin-converting enzyme (ACE) inhibitors act by decreasing production of angiotensin II and by potentiating the effects of bradykinin by inhibition of its breakdown. Bradykinin exerts part of its effects via vasodilating prostaglandins. Since the cyclooxygenase (COX)-inhibitors, e.g. aspirin and non-steroidal anti-inflammatory drugs, NSAIDs, block the formation of prostaglandins patients may not receive full advantage of ACE-inhibition if they are treated with an ACE-inhibitor and a COX-inhibitor. In study I the renal effects of low-dose aspirin and the NSAID diclofenac in patients with congestive heart failure treated with ACE-inhibitors were evaluated. A single dose of diclofenac was found to significantly impair the renal function. No differences were found between low-dose aspirin and placebo. In study II the negative renal effects of COX-inhibitors in elderly, healthy subjects treated with an ACE-inhibitor after activation of the renin-angiotensin system were quantified. Activation of the renin-angiotensin system was achieved by pre-treatment with a diuretic and an ACE-inhibitor. Diclofenac induced reductions in renal function and after pre-treatment the reductions were even more pronounced. Angiotensin-receptor blockers (ARBs) block the angiotensin II action with no significant effect on bradykinin. Consequently, ARBs should not affect prostaglandin synthesis and not interact with COX-inhibitors the same way as ACE-inhibitors do. In study III elderly, healthy volunteers had pre-treatment as in study II but during one of the pre-treatment periods an ARB was given together with the diuretic. Surprisingly, no significant differences were found in renal impairment between ACE-inhibitors and ARBs. Study IV investigated the dose dependency of renal effects of aspirin with ACE-inhibitor treatment. Elderly, healthy volunteers were pre-treated as in study II and were randomised into two groups: one group received doses of placebo and 160 mg, the other group received doses of 80 mg and 320 mg. The results showed a clear dose dependency for the renal effects of aspirin. The renal effects were of clinical importance from a dose of at least 160 mg. In summary, this thesis suggests that NSAIDs should be avoided in patients with congestive heart failure, or only used under strict supervision. ACE-inhibitors and ARBs are equally sensitive to renal impairment from COX-inhibitors and aspirin shows a clear dose dependent interaction with ACE-inhibitors on renal function. If treatment with aspirin is mandatory a dose equal to or lower than 80 mg should be used

Reduced forced expiratory volume is associated with increased incidence of atrial fibrillation: the Malmo Preventive Project.

Reduced forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) have been associated with increased incidence of cardiovascular diseases. However, whether reduced lung function is also a risk factor for incidence of atrial fibrillation (AF) is still unclear. We aimed to determine whether lung function predicted AF in the Malmö Preventive Project, a large population-based cohort with a long follow-up.METHODS AND RESULTS: The study population consisted of 7674 women and 21 070 men, mean age 44.6 years. The cohort was followed on average for 24.8 years, during which time 2669 patients were hospitalized due to AF. The incidence of AF in relationship to quartiles of FEV1 and FVC and per litre decrease at baseline was determined using a Cox proportional hazards model adjusted for age, height, weight, current smoking status, systolic blood pressure, erythrocyte sedimentation rate, and fasting blood glucose. Forced expiratory volume in one second was inversely related to incidence of AF (per litre reduction in FEV1) hazard ratio (HR): 1.39 [95% confidence interval (CI): 1.16-1.68; P = 0.001] for women, and HR: 1.20 (95% CI: 1.13-1.29; P < 0.0001) for men. Forced vital capacity was also inversely related to incidence of AF (per litre reduction in FVC) HR: 1.20 (95% CI: 1.03-1.41; P = 0.020) for women, and HR: 1.08 (95% CI: 1.02-1.14; P = 0.01) for men. This relationship was consistent in non-smokers as well as smokers, and among individuals younger than the median age of 45.8 years or normotensive subjects.CONCLUSION: Impaired lung function is an independent predictor of AF. This may explain some risk of AF that is currently unaccounted for

Evaluation of pre-arrest morbidity score and prognosis after resuscitation score and other clinical variables associated with in-hospital cardiac arrest in southern Sweden.

To evaluate pre-arrest morbidity score (PAM), prognosis after resuscitation score (PAR) and to identify additional clinical variables associated with survival after in-hospital cardiac arrest (IHCA) treated with cardiopulmonary resuscitation (CPR)

Renal effects of aspirin are clearly dose-dependent and are of clinical importance from a dose of 160 mg.

BACKGROUND: High doses of aspirin counteract the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. It is not known how low-dose aspirin, with concomitant ACE-inhibitor treatment, affects renal function. AIM: To study renal effects of different doses of aspirin in elderly healthy volunteers who had an activated renin-angiotensin system. METHODS: Sixteen subjects each received two different doses of aspirin (0 and160 mg or 80 and 320 mg) after pre-treatment with bendroflumethiazide and enalapril, in a randomised double-blind, cross-over fashion. RESULTS: Least square means of the observations 30 to 180 min after dosing, showed that urine flow, GFR, excretion rates of sodium, osmolality clearance and free water clearance were significantly decreased in a dose-dependent manner. Urine flow, sodium excretion rate and free water clearance were significantly lower with 320 mg aspirin vs. 0 mg and 80 mg, and GFR was significantly lower with 320 mg vs. 80 mg. Urine flow, sodium excretion rate, free water and osmolality clearance was significantly lower with aspirin 160 mg vs. 0 mg. CONCLUSION: The dose-dependent renal effects of aspirin are of clinical importance from a dose of 160 mg. The adverse influence of aspirin doses higher than 80 mg should be taken into consideration in patients with heart failure

Risk factor changes and incident atrial fibrillation among middle-aged men in the Malmö Preventive Project cohort

Aims: To determine whether risk factor changes over 6 years were associated with the incidence of atrial fibrillation (AF)among middle-aged men in the Malmo ̈ Preventive Project (MPP) cohort.Methods and results: In total, 5633 men (mean age 47.0 years at baseline) underwent two screening examinations, separated by an average of6 years. The annual rate at which systolic blood pressure (SBP), diastolic blood pressure (DBP), weight, fasting blood glucose (FBG), blood glucose at 2-h oral glucose tolerance test (OGTT), and screening spirometry values changed wascalculated and analysed in relation to incident AF, using Cox and competing risks regression to determine hazard ratios (HRs) and 95% confidence intervals (CIs). Mean follow-up time + SD from rescreening was 22.3 + 7.4 years. Signifi-cant associations were found between the annual increase of SBP (HR: 1.04, 95% CI: 1.01 – 1.07, P=0.003 per mmHg),DBP (HR: 1.06, 95% CI: 1.01 – 1.1, P=0.024 per mmHg), FBG (HR: 2.11, 95% CI: 1.44 – 3.12, P=0.0001 per mmol/L),and weight (HR: 1.14, 95% CI: 1.05–1.24,=0.003 per kg) on the one hand and incident AF on the other, after full adjustment for baseline age, height, weight, SBP, FBG, smoking status, sedentary lifestyle, anti-hypertensive treatment,screening year, and low socioeconomic status.Conclusion: The age-adjusted annual rates of increase in SBP, DBP, weight, and FBG in mid-life are associated with AF incidence in men. This raises the question of whether preventive measu

Concomitant use of dronedarone with dabigatran in patients with atrial fibrillation in clinical practice.

Dronedarone is a strong P-glycoprotein inhibitor with a potential to increase bioavailability of dabigatran. We sought to measure and report plasma concentrations of dabigatran in patients with atrial fibrillation (AF) on concomitant dronedarone treatment