COVID-19 among the inhabitants of the slums in the city of Buenos Aires: a population-based study.

OBJECTIVE: To summarise the unfolding of the COVID-19 epidemic among slum dwellers and different social strata in the city of Buenos Aires during the first 20 weeks after the first reported case. DESIGN: Observational study using a time-series analysis. Natural experiment in a big city. SETTING: Population of the city of Buenos Aires and the integrated health reporting system records of positive RT-PCR for COVID-19 tests. PARTICIPANTS: Records from the Argentine Integrated Health Reporting System for all persons with suspected and RT-PCR-confirmed diagnosis of COVID-19 between 31 January and 14 July 2020. OUTCOMES: To estimate the effects of living in a slum on the standardised incidence rate of COVID-19, corrected Poisson regression models were used. Additionally, the impact of socioeconomic status was performed using an ecological analysis at the community level. RESULTS: A total of 114 052 people were tested for symptoms related with COVID-19. Of these, 39 039 (34.2%) were RT-PCR positive. The incidence rates for COVID-19 towards the end of the 20th week were 160 (155 to 165) per 100 000 people among the inhabitants who did not reside in the slums (n=2 841 997) and 708 (674 to 642) among slums dwellers (n=233 749). Compared with the better-off socioeconomic quintile (1.00), there was a linear gradient on incidence rates: 1.36 (1.25 to 1.46), 1.61 (1.49 to 1.74), 1.86 (1.72 to 2.01), 2.94 (2.74 to 3.16) from Q2 to Q5, respectively. Slum dwellers were associated with an incidence rate of 14.3 (13.4 to 15.4). CONCLUSIONS: The distribution of the epidemic is socially conditioned. Slum dwellers are at a much higher risk than the rest of the community. Slum dwellers should not be considered just another risk category but an entirely different reality that requires policies tailored to their needs.

Circulating cardiac biomarkers and postoperative atrial fibrillation in the OPERA trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and predicts increased morbidity and mortality. Identification of patients at high risk of POAF with the help of circulating biomarkers may enable early preventive treatment but data are limited, especially in contemporary surgical patients. METHODS: Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at enrollment, on the morning of cardiac surgery, at end surgery, and 2 days postsurgery in 562 patients undergoing cardiac surgery, randomized to perioperative supplementation with oral fish oil or placebo in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial (OPERA). The primary endpoint was incident POAF lasting ≥ 30 s, centrally adjudicated and confirmed electrocardiographically. RESULTS: Higher levels of NT-proBNP and hs-cTnT before surgery were associated with older age, renal or cardiac dysfunction and EuroSCORE. NT-proBNP peaked on postoperative day 2 (2172 [1238-3758] ng/L, median [Q1-Q3]), while hs-cTnT peaked at the end of surgery (373 [188-660] ng/L). Fish oil supplementation did not alter the time course of the cardiac biomarkers (P > 0.05). Concentrations of NT-proBNP or hs-cTnT, on the morning of surgery, or changes in their level between morning of surgery and postsurgery, were not significantly associated with POAF after adjustment for clinical and surgical characteristics. CONCLUSION: Among patients undergoing cardiac surgery, NT-proBNP and hs-cTnT are related to clinical and surgical characteristics, have different perioperative time courses but are not independently associated with risk of POAF.

Plasma phospholipid omega-3 fatty acids and incidence of postoperative atrial fibrillation in the OPERA trial.

BACKGROUND: Long-chain polyunsaturated omega-3 fatty acids (n-3 PUFA) demonstrated antiarrhythmic potential in experimental studies. In a large multinational randomized trial (OPERA), perioperative fish oil supplementation did not reduce the risk of postoperative atrial fibrillation (PoAF) in cardiac surgery patients. However, whether presupplementation habitual plasma phospholipid n-3 PUFA, or achieved or change in n-3 PUFA level postsupplementation are associated with lower risk of PoAF is unknown. METHODS AND RESULTS: In 564 subjects undergoing cardiac surgery between August 2010 and June 2012 in 28 centers across 3 countries, plasma phospholipid levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were measured at enrollment and again on the morning of cardiac surgery following fish oil or placebo supplementation (10 g over 3 to 5 days, or 8 g over 2 days). The primary endpoint was incident PoAF lasting ≥ 30 seconds, centrally adjudicated, and confirmed by rhythm strip or ECG. Secondary endpoints included sustained (≥ 1 hour), symptomatic, or treated PoAF; the time to first PoAF; and the number of PoAF episodes per patient. PoAF outcomes were assessed until hospital discharge or postoperative day 10, whichever occurred first. Relative to the baseline, fish oil supplementation increased phospholipid concentrations of EPA (+142%), DPA (+13%), and DHA (+22%) (P < 0.001 each). Substantial interindividual variability was observed for change in total n-3 PUFA (range = -0.7% to 7.5% after 5 days of supplementation). Neither individual nor total circulating n-3 PUFA levels at enrollment, morning of surgery, or change between these time points were associated with risk of PoAF. The multivariable-adjusted OR (95% CI) across increasing quartiles of total n-3 PUFA at enrollment were 1.0, 1.06 (0.60 to 1.90), 1.35 (0.76 to 2.38), and 1.19 (0.64 to 2.20); and for changes in n-3 PUFA between enrollment and the morning of surgery were 1.0, 0.78 (0.44 to 1.39), 0.89 (0.51 to 1.55), and 1.01 (0.58 to 1.75). In stratified analysis, demographic, medication, and cardiac parameters did not significantly modify these associations. Findings were similar for secondary PoAF endpoints. CONCLUSIONS: Among patients undergoing cardiac surgery, neither higher habitual circulating n-3 PUFA levels, nor achieved levels or changes following short-term fish oil supplementation are associated with risk of PoAF.

Exploratory analysis on the use of statins with or without n-3 PUFA and major events in patients discharged for acute myocardial infarction: an observational retrospective study.

BACKGROUND: Combined treatment (CT) with statins and polyunsaturated fatty acids (n-3 PUFA) resulted in a reduction of death and major cardiovascular events when administered after a myocardial infarction (MI). However, recent data suggests that CT may be ineffective because patients are currently treated aggressively and the risk may not be further decreased. We aimed to study the prevalence and the results on major outcomes with CT among patients discharged with a MI in Italy. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective cohort study that used linked hospital discharge, prescription databases and vital statistics containing information on 14,704 patients who were discharged for MI between 1/2003 and 12/2003 in 117 hospitals in Italy. All analyses were time-dependent and adjusted for major confounders. Sensibility and paired matched analysis were conducted to further verify main results. A total of 11,532 (78.4%) filled a prescription for a statin. Of these, 4302 (37.3%) were on CT. There were 45,528 patients/years of follow-up. As compared with statins alone, CT was associated with an adjusted higher survival rate (HR = 0.59 [0.52-0.66], p<0.001), survival free of atrial fibrillation (HR = 0.78 [0.71-0.86], p<0.001) and survival free of new heart failure development (HR = 0.81 [0.74-0.88], p<0.001), but not with re-infarction (HR = 0.94 [0.86-1.02], p<0.127). Clinically this means that between 2 to 3 fewer events for each 100 patients/year were obtained in the group under CT. CONCLUSIONS/SIGNIFICANCE: Among a representative sample of patients discharged with MI in Italy, we observed clinically significant synergism between the effects of statins and n-3 PUFA for most cardiovascular outcomes, including all cause mortality.

N-3 polyunsaturated fatty acids to prevent atrial fibrillation: updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Previous studies have suggested that n-3 polyunsaturated fatty acids (n-3 PUFAs) have antiarrhythmic effects on atrial fibrillation (AF). We aimed to assess the effects of therapy with n-3 PUFAs on the incidence of recurrent AF and on postoperative AF. METHODS AND RESULTS: Electronic searches were conducted in Web of Science, Medline, Biological Abstracts, Journal Citation Reports, and the Cochrane Central Register of Controlled Trials databases. In addition, data from the recently completed FORωARD and OPERA trials were included. We included randomized controlled trials comparing treatment with n-3 PUFAs versus control to (1) prevent recurrent AF in patients who underwent reversion of AF or (2) prevent incident postoperative AF after cardiac surgery. Of identified studies, 12.9% (16 of 124) were included, providing data on 4677 patients. Eight studies (1990 patients) evaluated n-3 PUFA effects on AF recurrence among patients with reverted AF and 8 trials (2687 patients) on postoperative AF. Pooled risk ratios through random-effects models showed no significant effects on AF recurrence (RR, 0.95; 95% CI, 0.79 to 1.13; I(2), 72%) or on postoperative AF (0.86; 95% CI, 0.71 to 1.04; I(2), 53.1%). A funnel plot suggested publication bias among postoperative trials but not among persistent AF trials. Meta-regression analysis did not find any relationship between doses and effects (P=0.887 and 0.833 for recurrent and postoperative AF, respectively). CONCLUSIONS: Published clinical trials do not support n-3 PUFAs as agents aimed at preventing either postoperative or recurrent AF. CLINICAL TRIAL REGISTRATION: URL: http://www.crd.york.ac.uk/PROSPERO. Unique Identifier: CRD42012002199.

Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) trial.

OBJECTIVES: The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm. BACKGROUND: Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF. RESULTS: There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65). CONCLUSIONS: Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF. (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation [FORWARD]; NCT00597220).

Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.

CONTEXT: Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results. OBJECTIVE: To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF. DESIGN, SETTING, AND PATIENTS: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. INTERVENTION: Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. MAIN OUTCOME MEASURE: Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. RESULTS: At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events. CONCLUSION: In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00970489.

The ω-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial--rationale and design.

Postoperative atrial fibrillation/flutter (PoAF) commonly complicates cardiac surgery, occurring in 25% to 60% of patients. Postoperative atrial fibrillation/flutter is associated with significant morbidity, higher long-term mortality, and increased health care costs. Novel preventive therapies are clearly needed. In experiments and short-term trials, seafood-derived long-chain ω-3 polyunsaturated fatty acids (PUFAs) influence several risk factors that might reduce risk of PoAF. A few small and generally underpowered trials have evaluated effects of ω-3-PUFAs supplementation on PoAF with mixed results. The OPERA trial is an appropriately powered, investigator-initiated, randomized, double-blind, placebo-controlled, multinational trial to determine whether perioperative oral ω-3-PUFAs reduces occurrence of PoAF in patients undergoing cardiac surgery. Additional aims include evaluation of resource use, biologic pathways and mechanisms, postoperative cognitive decline, and safety. Broad inclusion criteria encompass a "real-world" population of outpatients and inpatients scheduled for cardiac surgery. Treatment comprises a total preoperative loading dose of 8 to 10 g of ω-3-PUFAs or placebo divided over 2 to 5 days, followed by 2 g/d until hospital discharge or postoperative day 10, whichever comes first. Based on anticipated 30% event rate in controls, total enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to detect 25% reduction in PoAF. The OPERA trial will provide invaluable evidence to inform biologic pathways; proof of concept that ω-3-PUFAs influence cardiac arrhythmias; and potential regulatory standards and clinical use of this simple, inexpensive, and low-risk intervention to prevent PoAF.

The rationale and design of the FORomegaARD Trial: A randomized, double-blind, placebo-controlled, independent study to test the efficacy of n-3 PUFA for the maintenance of normal sinus rhythm in patients with previous atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with increased risk of death, thromboembolic complications, and a lowered quality of life. Despite this burden, pharmacologic agents for prevention of AF in patients who achieved normal sinus rhythm are of limited utility, mostly because of serious and frequent side effects. Thus, the availability of safer and more effective drugs may reduce the burden of disease. TRIAL DESIGN: Patients aged > or =21 years with previous symptomatic AF and who have recovered normal sinus rhythm will be randomized to 1 g daily of omega-3-acid ethyl esters or identical placebo. To be included in the trial, patients must have either (a) at least 2 symptomatic episodes of documented AF in the 6 months before randomization, with the last episode occurring in the 14 to 90 days before randomization (paroxysmal AF), or (b) successful electrical or pharmacologic cardioversion for persistent AF. Ethical committees of 71 cardiology centers in 16 provinces of Argentina have qualified and approved the protocol and are expected to enroll 1,400 patients to test the primary end point of efficacy, which is survival free of AF during follow-up. CONCLUSION: The Fish Oil Reserach with omega-3 for Atrial fibrillation Recurrence Delay (FORomegaARD) trial will determine whether pharmacologic supplementation with 1 g of omega-3-acid ethyl esters can reduce AF recurrence in patients with previous AF who have recovered normal sinus rhythm.

Omega-3 fatty acid supplementation reduces one-year risk of atrial fibrillation in patients hospitalized with myocardial infarction.

PURPOSE: Current strategies for avoiding atrial fibrillation (AF) are of limited value. We aim to assess the relationship between omega-3 fatty acids (n-3 PUFA) and AF occurrence in post-myocardial infarction (MI) patients. METHODS: A population study, linking hospital discharge records, prescription databases, and vital statistics, was conducted and included all consecutive patients with MI (ICD-9: 410) in six Italian local health authorities over a 3-year period. A propensity score (PS)-based, 5-to-1, greedy 1:1 matching algorithm was used to check consistency of results. Sensitivity analysis was performed to assess the robustness of findings. RESULTS: N-3 PUFA reduced the relative risk of the hospitalization for AF [hazard ratio (HR) 0.19, 95% CI 0.07-0.51] and was associated with a further and complementary reduction in all-cause mortality (HR 0.15, 95% CI 0.05-0.46). PS-based matched analysis and sensitivity analysis confirmed the main results. CONCLUSION: n-3 PUFA reduced both all-cause mortality and incidence of 1-year AF in patients hospitalized with MI.

Vitamin E increases the risk of developing heart failure after myocardial infarction: Results from the GISSI-Prevenzione trial.

OBJECTIVE: Although results from basic science suggested a protective role of vitamin E treatment in the prevention of cardiovascular disease, recent evidence indicates increased cardiovascular mortality due to vitamin E treatment. Recently, the HOPE trial showed an increment of the incidence of congestive heart failure (CHF) in patients treated with vitamin E. METHODS: We explored the effect of vitamin E on development of CHF in 8415 postinfarction patients without CHF at baseline, with an echocardiographic measure of left ventricular ejection fraction, who have been followed up for 3.5 years in the GISSI-Prevenzione trial. CHF during follow-up was defined as hospitalization or death for CHF. Cox regression models adjusted for relevant prognostic indicators were fitted. RESULTS: Main clinical characteristics were balanced in the 4202 and 4213 patients allocated vitamin E and control group, respectively. During follow-up, 220 patients (2.6%) developed CHF. Patients allocated vitamin E had a nonsignificant 20% (95% confidence intervals 0.92-1.56, P = 0.18) increased risk of developing CHF. Vitamin E treatment, however, was associated with a significant 50% increase (95% confidence intervals 1.03-2.20, P = 0.034) of CHF in patients with left ventricular dysfunction (ejection fraction < 50%). CONCLUSIONS: Our results confirm and extend previous evidence on the possible harmful effect of vitamin E on ventricular function in patients with cardiovascular disease. Available evidence should discourage the use of vitamin E in patients with left ventricular dysfunction.

Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids.

BACKGROUND: Sudden death (SD) has a major impact on mortality (M) in patients with left ventricular systolic dysfunction (SyD). In GISSI-Prevenzione, treatment with n-3 polyunsaturated fatty acids (PUFA) reduced M and SD in post-MI patients, but their effect in patients with SyD is unknown. METHODS: 11,323 patients with prior MI and NYHA class < or = II were recruited. After excluding patients with no ejection fraction (EF) measurement (1684), and those with missing data (n=9), 9630 patients were available for analysis. Multivariate Cox regression adjusted models were fitted. RESULTS: Compared to patients with EF > 50%, SyD patients had higher M (12.3% vs. 6.0%) and SD (3.4% vs. 1.4%) rates. PUFA reduced M similarly in patients with (RR 0.76 (0.60-0.96) P=0.02) and without SyD (RR 0.81 (0.59-1.10) P=0.17) (heterogeneity tests P=0.55). In contrast, the effect on SD was markedly asymmetrical: PUFA produced a marked reduction (RR 0.42 (0.26-0.67) P=0.0003) of risk in SyD patients whereas the effect was less evident (RR 0.89 (0.41-1.69) P=0.71) in patients with EF > 50% (heterogeneity tests P=0.07). There was a significant increase in SD with worsening EF (P test for trend=0.02), the benefit on SD in patients with EF < or = 40% being 4-fold higher than in those with EF > 50%. CONCLUSIONS: Increasing SyD is associated with elevated risk of SD and with increasing benefit from PUFA. The effect of PUFA on SD reduction was greater in patients with SyD. Prospective trials testing the effect of PUFA in populations with SyD are required.