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The Framingham Heart Study (FHS) was established in 1948 to improve understanding of the epidemiology of coronary heart disease (CHD) in the USA. In 1961, seminal work identified major risk factors for CHD (high blood pressure, high cholesterol levels and evidence on the electrocardiogram of left ventricular hypertrophy), which later formed the basis for multivariable 10-year and 30-year risk-prediction algorithms. The FHS cohorts now comprise three generations of participants (n ≈ 15,000) and two minority cohorts. The FHS cohorts are densely phenotyped, with recurring follow-up examinations and surveillance for cardiovascular and non-cardiovascular end points. Assessment of subclinical disease and physiological profiling of these cohorts (with the use of echocardiography, ambulatory electrocardiographic monitoring, exercise stress testing, cardiac CT, heart and brain MRI, serial vascular tonometry and accelerometry) have been performed repeatedly. Over the past decade, the FHS cohorts have undergone deep ‘omics’ profiling (including whole-genome sequencing, DNA methylation analysis, transcriptomics, high-throughput proteomics and metabolomics, and microbiome studies). The FHS is a rich, longitudinal, transgenerational and deeply phenotyped cohort study with a sustained focus on state-of-the-art epidemiological methods and technological advances to facilitate scientific discoveries.The Framingham Heart Study (FHS) has been collecting epidemiological data on cardiovascular risk factors and disease for >70 years. In this Timeline Perspectives article, the authors summarize the major achievements of the FHS, highlight some of the seminal publications and discuss how epidemiological research has changed and continues to evolve.

Key Points Women generally have lower age-adjusted incidence and prevalence of atrial fibrillation (AF) than men; however, given the greater longevity of women, the absolute number of men and women with AF is similar The prevalence of major risk factors differ by sex; women have higher prevalence of hypertension and valvular heart disease, and lower prevalence of coronary heart disease, than men Women are more likely to present with atypical symptoms, such as weakness and fatigue, have longer duration of symptoms, and report worse quality of life and more-frequent depression than men Female sex has been shown to be a risk factor for AF-related stroke or thromboembolism, myocardial infarction, and mortality, but has not been associated with incident heart failure or dementia Future research is needed to address the knowledge gaps in sex-specific differences in AF Differences between women and men with atrial fibrillation have received far less attention in recent years than sex-specific differences in coronary heart disease and stroke. In this Review, Ko et al . discuss sex-specific differences in the incidence, prevalence, risk factors, and pathophysiology of atrial fibrillation, and the clinical presentation and prognosis of patients with this prevalent arrhythmia. Atrial fibrillation (AF) is the most common sustained arrhythmia in women and men worldwide. During the past century, a range of risk factors has been associated with AF, severe complications from the arrhythmia have been identified, and its prevalence has been increasing steadily. Whereas evidence has accumulated regarding sex-specific differences in coronary heart disease and stroke, the differences between women and men with AF has received less attention. We review the current literature on sex-specific differences in the epidemiology of AF, including incidence, prevalence, risk factors, and genetics, and in the pathophysiology and the clinical presentation and prognosis of patients with this arrhythmia. We highlight current knowledge gaps and areas that warrant future research, which might advance understanding of variation in the risk factors and complications of AF, and ultimately aid more-tailored management of the arrhythmia.

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 in individuals with at least one elevated risk factor.

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. 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. 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. 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. NIH, NHLBI, NINDS, Deutsche Forschungsgemeinschaft.

ObjectivesNarrative medicine (NM) incorporates stories into health sciences paradigms as fundamental aspects of the human experience. The aim of this systematic review is to answer the research question: how effective is the implementation and evaluation of NM programmes in academic medicine and health sciences? We documented objectives, content and evaluation outcomes of NM programming to provide recommendations for future narrative-based education.MethodsWe conducted a systematic review of literature published through 2019 using five major databases: PubMed, Embase, PsycINFO, ERIC and MedEdPORTAL. Eligible NM programming included textual analysis/close reading of published literature and creative/reflective writing. Qualifying participants comprised individuals from academic medicine and health sciences disciplines. We reviewed and categorised programme goals, content and evaluation activities to assess participant satisfaction and programme efficacy. Two members of the research team assessed the risk of bias, independently screening records via a two-round, iterative process to reach consensus on eligibility.ResultsOf 1569 original citations identified, we selected 55 unique programmes (described in 61 records). In all, 41 (75%) programmes reported a form of evaluation; evaluation methods lacked consistency. Twenty-two programmes used quantitative evaluation (13 well described), and 33 programmes used qualitative evaluation (27 well described). Well-described quantitative evaluations relied on 32 different measures (7 validated) and showed evidence of high participant satisfaction and pre-post improvement in competencies such as relationship-building, empathy, confidence/personal accomplishment, pedagogical skills and clinical skills. An average of 88.3% of participants agreed or strongly agreed that the programme had positive outcomes. Qualitative evaluation identified high participant satisfaction and improvement in competencies such as relationship-building, empathy, perspective-taking/reflection, resilience and burnout detection/mitigation, confidence/personal accomplishment, narrative competence, and ethical inquiry.ConclusionEvaluation suggests that NM programming leads to high participant satisfaction and positive outcomes across various competencies. We suggest best practices and innovative future directions for programme implementation and evaluation.

Atrial fibrillation (AF) is associated with increased morbidity. P-wave indices (PWIs) measure atrial electrical function and are associated with AF. Study of PWI has been limited to single-cohort investigations, and their contributions to risk enhancement are unknown. We examined PWI from the FHS and ARIC study. We calculated 10-year AF risk using adjusted Cox models. We conducted cross-cohort meta-analyses for the PWI estimates and assessed their contributions to risk discrimination (c statistic), net reclassification index, and integrated discrimination improvement. After exclusions, the analysis included 3,110 FHS (62.6 ± 9.8 years, 56.9% women) and 8,254 ARIC participants (62.3 ± 5.6 years, 57.3% women, 20.3% black race). Over 10 years, 217 FHS and 458 ARIC participants developed AF. In meta-analysis, P-wave duration >120 milliseconds was significantly associated with AF (hazard ratio 1.55, 95% CI 1.29-1.85) compared with ≤120 milliseconds. P-wave area was marginally but not significantly related to AF (hazard ratio 1.31, 95% CI 0.95-1.80). P-wave terminal force was strongly associated with AF in ARIC but not FHS. P-wave indices had a limited contribution toward predictive risk beyond traditional risk factors and markers. P-wave indices are intermediate phenotypes for AF. They are associated with AF in cross-cohort meta-analyses but contribute minimally toward enhancing risk prediction.

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and increases risks of stroke, heart failure, and death. The CHARGE-AF risk score was developed to predict incident AF in three American cohorts and it was validated in two European cohorts. The CHA2DS2-VASc risk score was derived to predict risk of stroke, peripheral embolism, and pulmonary embolism in individuals with AF, but it has been increasingly used for AF risk prediction. We compared CHARGE-AF risk score versus CHA2DS2-VASc risk score for incident AF risk in a community-based cohort. We studied Framingham Heart Study participants aged 46 to 94 years without prevalent AF and with complete covariates. We predicted AF risk using Fine-Gray proportional sub-distribution hazards regression. We used the Wald χ2 statistic for model fit, C-statistic for discrimination, and Hosmer-Lemeshow (HL) χ2 statistic for calibration. We included 9722 observations (mean age 63.9 ± 10.6 years, 56% women) from 4548 unique individuals: 752 (16.5%) developed incident AF and 793 (17.4%) died. The mean CHARGE-AF score was 12.0 ± 1.2 and the sub-distribution hazard ratio (sHR) for AF per unit increment was 2.15 (95% CI, 99-131%; P < .0001). The mean CHA2DS2-VASc score was 2.0 ± 1.5 and the sHR for AF per unit increment was 1.43 (95% CI, 37%-51%; P < .0001). The CHARGE-AF model had better fit than CHA2DS2-VASc (Wald χ2 = 403 vs 209, both with 1 df), improved discrimination (C-statistic = 0.75, 95% CI, 0.73-0.76 vs C-statistic = 0.71, 95% CI, 0.69-0.73), and better calibration (HL χ2 = 5.6, P = .69 vs HL χ2 = 28.5, P < .0001). The CHARGE-AF risk score performed better than the CHA2DS2-VASc risk score at predicting AF in a community-based cohort.

Atrial fibrillation (AF) is associated with a five-fold increased risk of stroke and a two-fold increased risk of death. We aimed to quantify changes in new diagnoses of AF following the onset of the COVID-19 pandemic. Investigating changes in new diagnoses of AF is of relevance because delayed diagnosis interferes with timely treatment to prevent stroke, heart failure, and death. Using De-identified Optum's Clinformatics® Data Mart, we identified 19,500,401 beneficiaries continuously enrolled for 12 months in 2016-Q3 2020 with no history of AF. The primary outcome was new AF diagnoses per 30-day interval. Secondary outcomes included AF diagnosis in the inpatient setting, AF diagnosis in the outpatient setting, and ischemic stroke as initial manifestation of AF. We constructed seasonal autoregressive integrated moving average models to quantify changes in new AF diagnoses after the onset of the COVID-19 pandemic (3/11/2020, date of pandemic declaration). We tested whether changes in the new AF diagnoses differed by race and ethnicity. The average age of study participants was 51.0±18.5 years, and 52% of the sample was female. During the study period, 2.7% of the study sample had newly-diagnosed AF. New AF diagnoses decreased by 35% (95% CI, 21%-48%) after the onset of the COVID-19 pandemic, from 1.14 per 1000 individuals (95% CI, 1.05-1.24) to 0.74 per 1000 (95% CI, 0.64 to 0.83, p-value<0.001). New AF diagnoses decreased by 37% (95% CI, 13%- 55%) in the outpatient setting and by 29% (95% CI, 14%-43%) in the inpatient setting. The decrease in new AF diagnoses was similar across racial and ethnic subgroups. In a nationwide cohort of 19.5 million individuals, new diagnoses of AF decreased substantially following the onset of the COVID-19 pandemic. Our findings evidence pandemic disruptions in access to care for AF, which are concerning because delayed diagnosis interferes with timely treatment to prevent complications.

Galectin 3 (Gal-3) is a potential mediator of cardiac fibrosis, and Gal-3 concentrations predict incident heart failure. The same mechanisms that lead to cardiac fibrosis in heart failure may influence development of atrial fibrosis and atrial fibrillation (AF). We examined the association of Gal-3 and incident AF in the community. Plasma Gal-3 concentrations were measured in 3,306 participants of the Framingham Offspring cohort who attended the sixth examination cycle (1995-1998, mean age 58 years, 54% women). Cox proportional hazards regression models were used to assess the association of baseline Gal-3 concentrations and incident AF. Over a median follow-up period of 10 years, 250 participants developed incident AF. Crude incidence rates of AF by increasing sex-specific Gal-3 quartiles were 3.7%, 5.9%, 9.1%, and 11.5% (log-rank test P < .0001). In age- and sex-adjusted analyses, each 1-SD increase in loge-Gal-3 was associated with a 19% increased hazard of incident AF (hazard ratio 1.19, 95% CI 1.05-1.36, P = .009). This association was not significant after adjustment for traditional clinical AF risk factors (hazard ratio 1.12, 95% CI 0.98-1.28, P = .10). Higher circulating Gal-3 concentrations were associated with increased risk of developing AF over the subsequent 10 years in age- and sex-adjusted analyses but not after accounting for other traditional clinical AF risk factors. Our results do not support a role for Gal-3 in AF risk prediction. Further studies are needed to evaluate whether Gal-3 plays a role in the development of AF substrate similar to HF.

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. 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. 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). 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. US National Institutes of Health.