Asthma and incident coronary heart disease: an observational and Mendelian randomisation study.

BACKGROUND: Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings. METHODS: First, we conducted an observational study using UK medical records to match asthma patients 1:1, by age, sex and general practitioner (GP) practice, to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium (TAGC) and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium (CARDIoGRAM). Using 64 asthma single nucleotide polymorphisms, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy. RESULTS: In our observational study (n=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR 1.06, 95% CI 1.01-1.13); after accounting for healthcare behaviour, we found no association (model 2: HR 0.99, 95% CI 0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR 1.11, 95% CI 1.01-1.21; males: HR 0.91, 95% CI 0.84-0.98). Our MR study (n=589 875) found no association between asthma and CHD (OR 1.01, 95% CI 0.98-1.04) and no modification by sex. CONCLUSIONS: Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.

Dementia in former amateur and professional contact sports participants: population-based cohort study, systematic review, and meta-analysis.

Background: Although there is growing evidence that former professional athletes from sports characterised by repetitive head impact subsequently experience an elevated risk of dementia, the occurrence of this disorder in retired amateurs, who represent a larger population, is uncertain. The present meta-analysis integrates new results from individual-participant analyses of a cohort study of former amateur contact sports participants into a systematic review of existing studies of retired professionals and amateurs. Methods: The cohort study comprised 2005 male retired amateur athletes who had competed internationally for Finland (1920-1965) and a general population comparison group of 1386 age-equivalent men. Dementia occurrence was ascertained from linked national mortality and hospital records. For the PROSPERO-registered (CRD42022352780) systematic review, we searched PubMed and Embase from their inception to April 2023, including cohort studies published in English that reported standard estimates of association and variance. Study-specific estimates were aggregated using random-effect meta-analysis. An adapted Cochrane Risk of Bias Tool was used to assess study quality. Findings: In the cohort study, up to 46 years of health surveillance of 3391 men gave rise to 406 dementia cases (265 Alzheimer's disease). After adjustment for covariates, former boxers experienced elevated rates of dementia (hazard ratio: 3.60 [95% CI 2.46, 5.28]) and Alzheimer's disease (4.10 [2.55, 6.61]) relative to general population controls. Associations were of lower magnitude in retired wrestlers (dementia: 1.51 [0.98, 2.34]; Alzheimer's disease: 2.11 [1.28, 3.48]) and soccer players (dementia: 1.55 [1.00, 2.41]; Alzheimer's disease: 2.07 [1.23, 3.46]), with some estimates including unity. The systematic review identified 827 potentially eligible published articles, of which 9 met our inclusion criteria. These few retrieved studies all sampled men and the majority were of moderate quality. In sport-specific analyses according to playing level, there was a marked difference in dementia rates in onetime professional American football players (2 studies; summary risk ratio: 2.96 [95% CI 1.66, 5.30]) relative to amateurs in whom there was no suggestion of an association (2 studies; 0.90 [0.52, 1.56]). For soccer players, while dementia occurrence was raised in both erstwhile professionals (2 studies; 3.61 [2.92, 4.45]) and amateurs (1 study; 1.60 [1.11, 2.30]) there was again a suggestion of a risk differential. The only studies of boxers comprised former amateurs in whom there was a tripling in the rates of dementia (2 studies; 3.14 [95% CI 1.72, 5.74]) and Alzheimer's disease (2 studies; 3.07 [1.01, 9.38]) at follow-up compared to controls. Interpretation: Based on a small number of studies exclusively sampling men, former amateur participants in soccer, boxing, and wrestling appeared to experience an elevated risk of dementia relative to the general population. Where data allowed comparison, there was a suggestion that risks were greater amongst retired professionals relative to amateurs in the sports of soccer and American football. Whether these findings are generalisable to the contact sports not featured, and to women, warrants examination. Funding: This work was unfunded.

Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study.

BACKGROUND: High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals. METHODS: In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements. RESULTS: In 7,293 individuals (mean 58 ± 7 years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4 years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (Pinteraction < 0.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75). CONCLUSIONS: Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk.

Aortic Pulse Wave Velocity as Adjunct Risk Marker for Assessing Cardiovascular Disease Risk: Prospective Study.

BACKGROUND: Aortic pulse wave velocity is a noninvasive measure of aortic stiffness and arterial aging. Its current value in cardiovascular risk estimation practice is unknown. We aimed to establish whether aortic pulse wave velocity identified individuals with higher risk of incident major adverse cardiovascular events and improved performance of the American Heart Association/American College of Cardiology atherosclerotic cardiovascular disease risk score. METHODS: This prospective analysis included 3837 Whitehall II cohort participants screened in 2008 to 2009, and followed for 11.7 years (mean=10.3, SD=1.81), without history of stroke, myocardial infarction, or coronary heart disease. RESULTS: Mean age of the sample was 65.0 years (SD=5.6), 2831 participants (73.8%) were male and mean atherosclerotic cardiovascular disease risk score was 13.8%. At the end of follow-up, 411 individuals (10.7%) had suffered a major cardiovascular event. Those in the highest aortic pulse wave velocity quartile were at high risk (hazard ratio, 2.99 [95% CI, 2.25-3.97]) and reached the threshold for statin medication (7.5% risk) after 5 years whereas others reached it after 10 years (difference P<0.001). The addition of aortic pulse wave velocity to the risk score improved the C statistic (0.68 versus 0.67, P=0.03) and net reclassification index (4.6%, P=0.04 and 11.3%, P=0.02). CONCLUSIONS: Our results show that aortic stiffness predicted major adverse cardiovascular events in a cohort of elderly individuals, improving the performance of a widely used cardiovascular disease risk estimator. Aortic pulse wave velocity measurement is scalable, radiation-free, and easy to perform. Further studies on its applicability in cardiovascular disease risk assessment in primary care settings are needed.

Adverse childhood experiences and incident coronary heart disease: a counterfactual analysis in the Whitehall II prospective cohort study.

OBJECTIVES: Adverse childhood experience is thought to be associated with risk of coronary heart disease, but it is not clear which experiences are cardiotoxic, and whether risk increases with the accumulation of adverse childhood experiences. METHODS: Participants were 5149 adults (72.6% men) in the Whitehall II cohort study. Parental death was recorded at phase 1 (median age in years 44.3), and 13 other adverse childhood experiences at phase 5 (55.3). We applied Cox proportional hazards regression with person-time from phase 5 to examine associations of adverse childhood experiences with incident coronary heart disease. We predicted hazard ratios according to count of the experiences, and examined dose-response effect. We finally estimated reduction of coronary heart disease in a hypothetical scenario, the absence of adverse childhood experiences. RESULTS: Among study participants, 62.9% had at least one adversity, with "financial problems" having the highest prevalence (26.1%). There were 509 first episodes of coronary heart disease during an average 12.9 years follow-up. Among 14 adverse childhood experiences in a multiply adjusted model, "parental unemployment" showed the highest hazard of coronary heart disease incidence (hazard ratio; 95% confidence interval: 1.53; 1.16 to 2.02). No dose-response effect was observed (constant for proportionality in hazard ratio: 1.05, 0.99 to 1.11). Based on the estimates of final model, in the absence of childhood adversities, we estimated a 6.0% reduction in coronary heart disease (0.94; 0.87 to 1.01), but the confidence interval includes one. CONCLUSION: Although individual adverse childhood experiences show some association with coronary heart disease, there is no clear relationship with the number of adverse experiences. Further research is required to quantify effects of multiple and combinations of adverse childhood experiences considering timing, duration, and severity.

Hypertension care cascade in Chile: a serial cross-sectional study of national health surveys 2003-2010-2017.

BACKGROUND: Trend data on hypertension prevalence and attainment indicators at each step of the care cascade (awareness, treatment, control) are required in Chile. This study aims to quantify trends (2003-2017) in prevalence and in the proportion of individuals with hypertension attaining each step of the care cascade among adults aged 17 years or older, and to assess the impact of lowering the blood pressure (BP) thresholds used to define elevated BP on these indicators. METHODS: We used data from 2003, 2010, and 2017 Chilean national health surveys. Each year we assessed levels of (1) mean systolic (SBP) and diastolic (DBP) blood pressure, (2) hypertension prevalence (BP ≥ 140/90 mmHg or use of antihypertensive treatment), and (3) awareness, treatment, and control. Logistic regression on pooled data was used to assess trends in binary outcomes; linear regression was used to assess trends in continuous SBP and DBP. We compared levels of hypertension prevalence using two sources to ascertain antihypertensive treatment (self-reported versus medicine inventory). The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines were used to re-define hypertension using lower thresholds (BP ≥ 130/80 mmHg). RESULTS: Hypertension prevalence was 34.0, 32.0 and 30.8% in 2003, 2010 and 2017, respectively. Levels of treated- and controlled-hypertension were significantly higher in 2017 than in 2003 (65% versus 41% for treatment, P < 0.001; 34% versus 14% for control, P < 0.001), while levels of awareness were stable (66% versus 59%, P = 0.130). Awareness, treatment, and control levels were higher among females in 2003, 2010, and 2017 (P < 0.001). Mean SBP and DBP decreased over the 15-year period, except for SBP among females on treatment. Adopting the 2017 ACC/AHA guidelines would increase hypertension prevalence by 17 and 55% in absolute and relative terms, respectively. CONCLUSIONS: Chile has experienced a positive population-wide lowering in blood pressure distribution which may be explained partly by a significant rise in levels of treated- and controlled-hypertension since 2003. Lowering the thresholds used to define elevated BP would substantially increase the financial public health challenge of further improving attainment levels at each step of the care cascade. Innovative and collaborative strategies are needed to improve hypertension management, especially among males.

Association of aortic stiffness with cognitive decline: Whitehall II longitudinal cohort study.

Aortic stiffness is associated with an increased risk of cardio- and cerebrovascular disease and mortality and may increase risk of dementia. The aim of the present study is to examine the association between arterial stiffness and cognitive decline in a large prospective cohort study with three repeated cognitive assessment over 7 years of follow-up. Aortic pulse wave velocity (PWV) was measured among 4300 participants (mean ± standard deviation age 65.1 ± 5.2 years) in 2007-2009 and categorized based on the tertiles: (lowest third: < 7.41 m/s), (middle third: 7.41-8.91 m/s), and (highest third: > 8.91 m/s). A global cognitive score was calculated in 2007-2009, 2012-2013, and 2015-2016 based on responses to memory, reasoning and fluency tests. Standardized global cognitive score (mean = 0, SD = 1) in highest third versus lowest third of PWV category was lower at baseline (- 0.12, 95% CI - 0.18, - 0.06). Accelerated 7-year cognitive decline was observed among individuals with the highest PWV [difference in 7-year cognitive change for highest third versus lowest third PWV: - 0.06, 95% CI - 0.11, - 0.01, P < 0.01]. Higher aortic stiffness was associated with faster cognitive decline. Clinicians may be able to use arterial stiffness severity as an indicator to administer prompt treatments to prevent or delay the onset of cognitive decline or dementia. Future studies need to determine whether early intervention of vascular stiffness is effective in delaying these outcomes.

Does Poorer Pulmonary Function Accelerate Arterial Stiffening?: A Cohort Study With Repeated Measurements of Carotid-Femoral Pulse Wave Velocity.

Whether poorer pulmonary function accelerates progression of arterial stiffness remains unknown as prior observational studies have not examined longitudinal changes in arterial stiffness in relation to earlier pulmonary function. Data (N=5342, 26% female) were drawn from the Whitehall II cohort study. Participants completed repeated assessments of forced expiratory volume in 1 second (FEV1, L) and carotid-femoral pulse wave velocity (cf-PWV, m/s) over 5 years. The effect of FEV1 on later cf-PWV and its progression was estimated using linear mixed-effects modeling. Possible explanatory mechanisms, such as mediation by low-grade systemic inflammation, common-cause explanation by preexisting cardiometabolic risk factors, and reverse-causation bias, were assessed. Poorer pulmonary function was associated with later higher cf-PWV and its subsequent progression (cf-PWV 5-year change 0.09, 95% CI 0.03-0.17 per SD lower FEV1) after adjustment for age, sex, ethnicity, heart rate, and mean arterial pressure. Decrease in pulmonary function was associated with later higher cf-PWV (0.17, 95% CI 0.04-0.30 in the top compared to bottom quartile of decline in FEV1). There was no evidence to support mediation by circulating CRP (C-reactive protein) or IL (interleukin)-6. Furthermore, arterial stiffness was not associated with later FEV1 after accounting for cardiometabolic status. In conclusion, poorer pulmonary function predicted future arterial stiffness. These findings support pulmonary function as a clinically important risk factor for arterial stiffness and provide justification for future intervention studies for pulmonary function based on its relationship with arterial stiffness.

First Colombian consensus on congenital Chagas and clinical approach for women of child-bearing age diagnosed with Chagas / Primer consenso colombiano sobre Chagas congénito y orientación clínica a mujeres en edad fértil con diagnóstico de Chagas

Congenital transmission of Chagas disease has not been extensively studied in Colombia, and there are no standardized processes in the health system regarding the specific diagnosis, treatment and follow-up of this disease. To generate recommendations on congenital Chagas disease and Chagas in women of childbearing age in Colombia, a consensus of experts was developed. An extensive literature search through the Medline database was carried out using the MeSH terms: «Chagas disease/congenital¼, «prevention and control¼, «diagnosis¼, «therapeutics¼ and «pregnancy¼. Appropriate abstracts were selected and the full texts were analyzed. The relevant information was synthesized, classified, and organized into tables and figures and was presented to a panel of experts, which was composed of 30 professionals from various fields. Based on the Delphi methodology, three rounds of consultation were conducted. The first and second rounds were based on electronic questionnaires that measured the level of consensus of each question among the participants. The third round was based on a face-to-face discussion focusing on those questions without consensus in the previous consultations. The evidence was adapted to national circumstances on a case-by-case basis, and the content the final document was approved. These recommendations are proposed for use in routine medical practice by health professionals in Colombia.

La transmisión congénita de la enfermedad de Chagas ha sido poco estudiada en Colombia y existen pocos procedimientos rutinarios en el sistema de salud para el manejo de esta enfermedad. Por ello se desarrolló un consenso de expertos dirigido a generar recomendaciones de diagnóstico y tratamiento de Chagas con- génito y orientación a mujeres en edad fértil. Con ese propósito se realizó una búsqueda extensiva de la literatura, empleando una combinación de términos Mes (Chagas, Chagas congénito, prevención, control, diagnóstico, tratamiento y embarazo) para reflejar el estado del arte en cada tema de interés. Después de ello, se leyeron los resúmenes y aquellos seleccionados para análisis del texto completo. La literatura relevante se sintetizo, clasifico y organizo en tablas y se presentó al panel de expertos, el cual estaba constituido por 30 profesionales en diferentes áreas. Mediante la metodología Delphi se realizaron 2 rondas de cuestionarios virtuales y una reunión presencial en los cuales se evaluaron los niveles de acuerdo entre los participantes. Los puntos con falta de consenso durante las 2 rondas virtuales se expusieron durante las mesas de discusión en la ronda presencial. La evidencia utilizada se adaptó a las particularidades nacionales según el caso y se aprobó el contenido del documento final. Se propone que estas recomendaciones sean usadas por profesionales de la salud en Colombia.

Risk factors for treatment interruption and severe adverse effects to benznidazole in adult patients with Chagas disease.

BACKGROUND: Etiological treatment of Chagas disease in chronic asymptomatic patients is still in debate and the adverse effects of traditional drugs are one of the main concerns in clinical practice. This study evaluated retrospectively the safety profile of benznidazole (BZN) and identified predictive factors for definite treatment interruption and development of severe reactions in adult patients treated with BZN in Colombia. METHODS: Retrospective follow-up study conducted by review of medical records of adults with chronic Chagas disease treated with BZN in Colombia. A parametric survival analysis based on a generalized gamma distribution was used for assessing risk factors for treatment interruption. A multinomial logistic regression model was used to estimate the probability of severe adverse drug reactions (ADRs). Statistical associations were expressed as time ratios (TR) and adjusted odds ratios (aOR) respectively. RESULTS: In total 224 adults patients treated with BZN were included; 172 (76.8%) completed the standard therapy (60 days of treatment), 205 (91.5%) presented ADRs and 52 cases (23.2%) required treatment interruption. The predominant symptoms were: rash (37.9%), itching (33.7%), epigastric pain (26.4%), abdominal bloating (24.2%) and nausea (22.1%). ADRs were mild (57.4%), moderate (35.5%) and severe (7.3%). Time to treatment interruption was significantly shorter when using doses of BZN ≥ 6 mg/kg/day (TR 0.55; 95% CI 0.39-0.76), presenting severe ADRs (TR 0.12; 95% CI: 0.07-0.19) and eosinophilia (TR 0.68; 95% CI: 0.49-0.94). Female sex (aOR 3.98; 95% CI 1.56-10.16), dose of BZN ≥ 6 mg/kg/day (aOR 1.41; 95% CI 1.17-1.70) and presence of > 3 ADRs (aOR 6.47; 95% CI 1.24-34.34) were considered as risk factors for developing severe ADRs. CONCLUSIONS: Dose, severity of ADRs, eosinophilia and female sex were the main predictors for treatment interruption or severe ADRs. The potential implications of these findings are discussed.

Correction: Molecular Diagnosis of Chagas Disease in Colombia: Parasitic Loads and Discrete Typing Units in Patients from Acute and Chronic Phases.

[This corrects the article DOI: 10.1371/journal.pntd.0004997.].

Risk factors associated with Chagas disease in pregnant women in Santander, a highly endemic Colombian area.

OBJECTIVE: To determine the prevalence and risk factors associated with Chagas disease in pregnant women in an endemic area of Santander, Colombia. METHODS: Cross-sectional study included 23 municipalities of Santander, Colombia. Serological IFAT and ELISA tests were undertaken to detect IgG anti- Trypanosoma cruzi. A questionnaire was conducted for assessing the risk factors of each participant. Newborns were evaluated at birth and followed up to 1 year of age to determine congenital infection. RESULTS: An overall prevalence of 3.2% (95% CI 2.4-4.2) among 1518 pregnant women was detected. Prevalences by provinces were as follows: Guanentina: 6.0% (95% CI 4.1-8.5), García Rovira: 2.9% (95% CI: 1.5-4.8) and Comunera: 0.4% (0.4-2.3). The main risk factors identified were age >32 years old (OR: 2.1; 95% CI: 1.1-3.9); currently having a thatched roof (OR: 11.8; CI95% 2.2-63.2) and a thatched roof during childhood (OR: 3.0; 95% CI: 1.4-6.6); having below primary school education level (OR: 4.6; 95% CI: 2.2-9.5); and a history of a close contact with the vector (triatomine bugs) at least once during their lifetime (OR: 6.9; 95% CI: 3.7-12.9). No congenital cases were detected by parasitological or serological techniques. CONCLUSIONS: Prevalence of Chagas disease in pregnant women is a potential source of infection in this Colombian endemic area. The main risk factors associated with seropositivity were related to conditions favouring the contact with the vector. The results show that it is necessary to continue an active surveillance in order to offer diagnosis and treatment to mothers and their newborns in addition to screening to pregnant women from endemic areas.

Primer consenso colombiano sobre Chagas congénito y orientación clínica a mujeres en edad fértil con diagnóstico de Chagas / First Colombian consensus on congenital Chagas and clinical approach to women of fertile age diagnosed with Chagas

La transmisión congénita de la enfermedad de Chagas ha sido poco estudiada en Colombia y existen pocos procedimientos rutinarios en el sistema de salud para el manejo de esta enfermedad. Por ello se desarrolló un consenso de expertos dirigido a generar recomendaciones de diagnóstico y tratamiento de Chagas congénito y orientación a mujeres en edad fértil. Con ese propósito se realizó una búsqueda extensiva de la literatura, empleando una combinación de términos MeSH (Chagas, Chagas congénito, prevención, control, diagnóstico, tratamiento y embarazo) para reflejar el estado del arte en cada tema de interés. Después de ello, se leyeron los resúmenes y aquellos seleccionados para análisis del texto completo. La literatura relevante se sintetizó, clasificó y organizó en tablas y se presentó al panel de expertos, el cual estaba constituido por 30 profesionales en diferentes áreas. Mediante la metodología Delphi se realizaron 2 rondas de cuestionarios virtuales y una reunión presencial en los cuales se evaluaron los niveles de acuerdo entre los participantes. Los puntos con falta de consenso durante las 2 rondas virtuales se expusieron durante las mesas de discusión en la ronda presencial. La evidencia utilizada se adaptó a las particularidades nacionales según el caso y se aprobó el contenido del documento final. Se propone que estas recomendaciones sean usadas por profesionales de la salud en Colombia.

Congenital transmission of Chagas disease has not been extensively studied in Colombia, and there are no standardized processes in the health system regarding the specific diagnosis, treatment and follow-up of this disease. In order to generate recommendations on congenital Chagas disease and Chagas in women of childbearing age in Colombia, a consensus of experts was developed. An extensive literature search through the Medline database was carried out using the MeSH terms: " Chagas disease/congenital " , " prevention and control " , " diagnosis " , " therapeutics " and " pregnancy " . Appropriate abstracts were selected and the full texts were analyzed. The relevant information was synthesized, classified, and organized into tables and figures and was presented to a panel of experts, which was composed of 30 professionals from various fields. Based on the Delphi methodology, three rounds of consultation were conducted. The first and second rounds were based on electronic questionnaires that measured the level of consensus of each question among the participants. The third round was based on a face-toface discussion focusing on those questions without consensus in the previous consultations. The evidence was adapted to national circumstances on a case-by-case basis, and the content the final document was approved. These recommendations are proposed for use in routine medical practice by health professionals in Colombia.