Direct oral anticoagulants (DOACs) have emerged as promising alternatives to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). ...Few meta-analyses have included all DOACs that have received FDA approval for these cardiovascular indications, and their overall comparisons against VKAs have shortcomings in data and methods. We provide an updated overall assessment of the efficacy and safety of those DOACs at dosages currently approved for NVAF or VTE, in comparison with VKAs.
We used data from Phase 3 randomized trials that compared an FDA-approved DOAC with VKA for primary prevention of stroke in patients with NVAF or for treatment of acute VTE.
Among trial participants with NVAF, DOAC recipients had a lower risk of stroke or systemic embolism Pooled Odds Ratio (OR) 0.76, 95% Confidence Interval (CI) (0.68-0.84), any stroke (0.80, 0.73-0.88), systemic embolism (0.56, 0.34-0.93), and total mortality (0.89, 0.84-0.95). Safety outcomes also showed a lower risk of fatal, major, and intracranial bleeding but higher risk for gastrointestinal bleeding (GIB). Patients with acute VTE randomized to DOACs had comparable risk of recurrent VTE and death (OR 0.88, 95% CI 0.75-1.03), recurrent DVT (0.83, 0.66-1.05), recurrent non-fatal PE (0.97, 0.75-1.25), and total mortality (0.94, 0.79-1.12). Safety outcomes for DOACs showed a lower risk of major, fatal, and intracranial bleeding, but similar risk of GIB.
Patients receiving DOACs for NVAF had predominantly superior efficacy and safety. Patients who were treated with DOACs for acute VTE had non-inferior efficacy, but an overall superior safety profile.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Comprehensive long-term data on atrial fibrillation trends in men and women are scant. We aimed to provide such data through analysis of the Framingham cohort over 50 years. ...Methods We investigated trends in incidence, prevalence, and risk factors for atrial fibrillation and its association with stroke and mortality after onset in 9511 participants enrolled in the Framingham Heart Study between 1958 and 2007. We analysed trends within 10 year groups (1958–67, 1968–77, 1978–87, 1988–97, and 1998–2007), stratified by sex. Findings During 50 years of observation (202 417 person-years), 1544 cases of new-onset atrial fibrillation occurred (of whom 723 47% were women). Between 1958–67 and 1998–2007, age-adjusted prevalence of atrial fibrillation quadrupled from 20·4 to 96·2 cases per 1000 person-years in men and from 13·7 to 49·4 cases per 1000 person-years in women; age-adjusted incidence increased from 3·7 to 13·4 new cases per 1000 person-years in men and from 2·5 to 8·6 new cases per 1000 person-years in women (ptrend <0·0001 for all comparisons). For atrial fibrillation diagnosed by electrocardiograph (ECG) during routine Framingham examinations, age-adjusted prevalence per 1000 person-years increased (12·6 in 1958–67 to 25·7 in 1998–2007 in men, ptrend =0·0007; 8·1 to 11·8 in women, ptrend =0·009). However, age-adjusted incidence of atrial fibrillation by Framingham Heart Study ECGs did not change significantly with time. Although the prevalence of most risk factors changed over time, their associated hazards for atrial fibrillation changed little. Multivariable-adjusted proportional hazards models revealed a 74% (95% CI 50–86%) decrease in stroke (hazards ratio HR 3·77, 95% CI 1·98–7·20 in 1958–1967 compared with 1998–2007; ptrend =0·0001) and a 25% (95% CI −3–46%) decrease in mortality (HR 1·34, 95% CI 0·97–1·86 in 1958–1967 compared with 1998–2007; ptrend =0·003) in 20 years following atrial fibrillation onset. Interpretation Trends of increased incidence and prevalence of atrial fibrillation in the community were probably partly due to enhanced surveillance. Measures are needed to enhance early detection of atrial fibrillation, through increased awareness coupled with targeted screening programmes and risk factor-specific prevention. Funding NIH, NHLBI, NINDS, Deutsche Forschungsgemeinschaft.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Morbidity from undiagnosed atrial fibrillation (AF) may be preventable with early detection. Many consumer wearables contain optical photoplethysmography (PPG) sensors to measure pulse rate. ...PPG-based software algorithms that detect irregular heart rhythms may identify undiagnosed AF in large populations using wearables, but minimizing false-positive detections is essential.
We performed a prospective remote clinical trial to examine a novel PPG-based algorithm for detecting undiagnosed AF from a range of wrist-worn devices. Adults aged ≥22 years in the United States without AF, using compatible wearable Fitbit devices and Android or iOS smartphones, were included. PPG data were analyzed using a novel algorithm that examines overlapping 5-minute pulse windows (tachograms). Eligible participants with an irregular heart rhythm detection (IHRD), defined as 11 consecutive irregular tachograms, were invited to schedule a telehealth visit and were mailed a 1-week ambulatory ECG patch monitor. The primary outcome was the positive predictive value of the first IHRD during ECG patch monitoring for concurrent AF.
A total of 455 699 participants enrolled (median age 47 years, 71% female, 73% White) between May 6 and October 1, 2020. IHRDs occurred for 4728 (1%) participants, and 2070 (4%) participants aged ≥65 years during a median of 122 (interquartile range, 110-134) days at risk for an IHRD. Among 1057 participants with an IHRD notification and subsequent analyzable ECG patch monitor, AF was present in 340 (32.2%). Of the 225 participants with another IHRD during ECG patch monitoring, 221 had concurrent AF on the ECG and 4 did not, resulting in an IHRD positive predictive value of 98.2% (95% CI, 95.5%-99.5%). For participants aged ≥65 years, the IHRD positive predictive value was 97.0% (95% CI, 91.4%-99.4%).
A novel PPG software algorithm for wearable Fitbit devices exhibited a high positive predictive value for concurrent AF and identified participants likely to have AF on subsequent ECG patch monitoring. Wearable devices may facilitate identifying individuals with undiagnosed AF.
URL: https://www.
gov; Unique identifier: NCT04380415.
Cardiovascular disease--a leading cause of morbidity and mortality among adults-is strongly influenced by platelet function through acute thrombotic and atherogenic mechanisms. Pathways that regulate ...platelet activity and lead to coronary occlusion are central to the pathogenesis of acute coronary syndromes. Platelet activation contributes to other thrombotic disorders and cardiovascular diseases, including stroke. Anucleate platelets are now understood to contain transcripts that might relate to other physiological or pathophysiological conditions, be released into the circulation, participate in protein formation, and engage in horizontal RNA transfer to other vascular cells. These platelet transcripts include microRNAs (miRNAs), which are small noncoding RNAs involved in many molecular processes, most notably regulation of gene expression. In platelets, these noncoding RNAs seem to participate in vascular homeostasis, inflammation, and platelet function. In addition, levels of platelet miRNAs in the circulation are associated with the presence or extent of cardiovascular diseases, such as atrial fibrillation and peripheral vascular disease. Accumulating data suggest mechanistic roles for platelet-derived miRNAs in haemostasis, thrombosis, and unstable coronary syndromes. In addition, evidence suggests that platelet-derived miRNAs might have important roles as biomarkers of cardiovascular disease susceptibility, prognosis, or treatment.
Among more than 11,000 participants, 1.7% had at least one false positive rapid antigen test on the basis of RT-PCR results. Persistent false positives tended to occur in women and in persons with ...autoimmune abnormalities.
Obesity, hypertension, and diabetes are independently associated with cardiac remodeling and frequently co-cluster. The conjoint and separate influences of these conditions on cardiac remodeling have ...not been investigated.
We evaluated 5,741 Framingham Study participants (mean age 50 years, 55% women) who underwent echocardiographic measurements of left ventricular (LV) mass (LVM), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', left atrial end-systolic (peak) dimension (LASD) and emptying fraction (LAEF). We used multivariable generalized linear models to estimate the adjusted-least square means of these measures according to cross-classified categories of body mass index (BMI; normal, overweight and obese), hypertension (yes/no), and diabetes (yes/no).
We observed statistically significant interactions of BMI category, hypertension, and diabetes with LVM, LVEF, GLS, and LAEF (p for all 3-way interactions <0.01). Overweight and obesity (compared to normal BMI), hypertension, and diabetes status were individually and conjointly associated with higher LVM and worse GLS (p<0.01 for all). We observed an increase of 34% for LVM and of 9% for GLS between individuals with a normal BMI and without hypertension or diabetes compared to obese individuals with hypertension and diabetes. Presence of hypertension was associated with higher LVEF, whereas people with diabetes had lower LVEF.
Obesity, hypertension, and diabetes interact synergistically to influence cardiac remodeling. These findings may explain the markedly heightened risk of heart failure and cardiovascular disease when these factors co-cluster.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractObjectiveTo examine the association between risk factor burdens—categorized as optimal, borderline, or elevated—and the lifetime risk of atrial fibrillation.DesignCommunity based cohort ...study.SettingLongitudinal data from the Framingham Heart Study.ParticipantsIndividuals free of atrial fibrillation at index ages 55, 65, and 75 years were assessed. Smoking, alcohol consumption, body mass index, blood pressure, diabetes, and history of heart failure or myocardial infarction were assessed as being optimal (that is, all risk factors were optimal), borderline (presence of borderline risk factors and absence of any elevated risk factor), or elevated (presence of at least one elevated risk factor) at index age.Main outcome measureLifetime risk of atrial fibrillation at index age up to 95 years, accounting for the competing risk of death.ResultsAt index age 55 years, the study sample comprised 5338 participants (2531 (47.4%) men). In this group, 247 (4.6%) had an optimal risk profile, 1415 (26.5%) had a borderline risk profile, and 3676 (68.9%) an elevated risk profile. The prevalence of elevated risk factors increased gradually when the index ages rose. For index age of 55 years, the lifetime risk of atrial fibrillation was 37.0% (95% confidence interval 34.3% to 39.6%). The lifetime risk of atrial fibrillation was 23.4% (12.8% to 34.5%) with an optimal risk profile, 33.4% (27.9% to 38.9%) with a borderline risk profile, and 38.4% (35.5% to 41.4%) with an elevated risk profile. Overall, participants with at least one elevated risk factor were associated with at least 37.8% lifetime risk of atrial fibrillation. The gradient in lifetime risk across risk factor burden was similar at index ages 65 and 75 years.ConclusionsRegardless of index ages at 55, 65, or 75 years, an optimal risk factor profile was associated with a lifetime risk of atrial fibrillation of about one in five; this risk rose to more than one in three a third in individuals with at least one elevated risk factor.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract Background Despite the widespread use of electrocardiographic changes to characterize patients presenting with acute myocardial infarction, little is known about recent trends in the ...incidence rates, treatment, and outcomes of patients admitted for acute myocardial infarction further classified according to the presence of ST-segment elevation. The objectives of this population-based study were to examine recent trends in the incidence and death rates associated with the 2 major types of acute myocardial infarction in residents of a large central Massachusetts metropolitan area. Methods We reviewed the medical records of 5383 residents of the Worcester (MA) metropolitan area hospitalized for either ST-segment elevation acute myocardial infarction (STEMI) or non-ST-segment acute myocardial infarction (NSTEMI) between 1997 and 2005 at 11 greater Worcester medical centers. Results The incidence rates (per 100,000) of STEMI decreased appreciably (121 to 77), whereas the incidence rates of NSTEMI increased slightly (126 to 132) between 1997 and 2005. Although in-hospital and 30-day case-fatality rates remained stable in both groups, 1-year postdischarge death rates decreased between 1997 and 2005 for patients with STEMI and NSTEMI. Conclusions The results of this study demonstrate recent decreases in the magnitude of STEMI, slight increases in the incidence rates of NSTEMI, and decreases in long-term mortality in patients with STEMI and NSTEMI. Our findings suggest that acute myocardial infarction prevention and treatment efforts have resulted in favorable decreases in the frequency of STEMI and death rates from the major types of acute myocardial infarction.
BACKGROUND:The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown.
METHODS:We estimated the lifetime risk of AF ...in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of ≈1000 AF-associated single-nucleotide polymorphisms. Clinical risk factor burden was calculated for each individual using a validated risk score for incident AF comprised of height, weight, systolic and diastolic blood pressure, current smoking status, antihypertensive medication use, diabetes mellitus, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk.
RESULTS:Among 4606 participants without AF at 55 years of age, 580 developed incident AF (median follow-up, 9.4 years; 25th–75th percentile, 4.4–14.3 years). The lifetime risk of AF >55 years of age was 37.1% and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at 55 years of age, those in low-polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval, 15.4−9.1), whereas those in high-risk tertiles had a risk of 48.2% (95% confidence interval, 41.3−55.1). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition (P<0.001).
CONCLUSIONS:In our community-based cohort, the lifetime risk of AF was 37%. Estimation of polygenic AF risk is feasible and together with clinical risk factor burden explains a substantial gradient in long-term AF risk.
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