Population Cohort Research Articles

Characteristics of sagittal spinopelvic alignment in Thai population: a cross-sectional study.

The prevalence of spinal deformity is a significant health concern often associated with the aging process. It is primarily attributed to the thickening of spinal joints, ligament pathologies, or the narrowing of the spinal canal, leading to compression of the spinal cord and nerve roots, and subsequently causing musculoskeletal problems. When considering corrective surgery for adult spinal deformities, it is crucial for spine surgeons to take into account the standard values of sagittal spinopelvic alignment. Notably, there is currently a lack of specific data on this aspect within the Thai population. Therefore, our study was focused on evaluating the alignment in the Thai population. To analyze sagittal spinopelvic alignment parameters in the asymptomatic Thai population and compare them with other populations. This study was designed as a cross-sectional analysis involving 194 participants, wherein the sagittal spinopelvic parameters were evaluated utilizing radiographic images. The measurements of the sagittal vertical axis (SVA), pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), and pelvic tilt (PT) were determined by averaging the assessments conducted by two orthopedic residents and a spine surgeon. In addition, participants' demographic information was obtained through questionnaires, and further analysis was performed on age, gender, and body mass index data. The study also encompassed the determination of correlations between various parameters and the comparison of these parameters with other populations. The body mass index (BMI) of the study participants demonstrated significant associations with several spinal parameters. Specifically, BMI showed significant correlations with sagittal vertical axis (SVA) (r = 0.2, p = 0.09), pelvic incidence (PI) (r = 0.4, p < 0.01), lumbar lordosis (LL) (r = 0.2, p = 0.02), sacral slope (SS) (r = -0.2, p = 0.02), and pelvic tilt (PT) (r = 0.2, p = 0.02). The SS exhibited a statistically significant decline with increasing age (p = 0.04). Furthermore, the mean SVA, PI, LL, SS, and PT differed significantly between the study participants and the Indian population. In addition, the SS was notably lower when compared to the European population. The study revealed the spinopelvic parameters in a cohort of healthy Thai population and observed a correlation between their body mass index (BMI) and pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), and pelvic tilt (PT). Notably, the average SS among Thai adults was found to be statistically lower than that of individuals from Indian, European Caucasian, Asian, and Mexican populations. These insights hold potential value as a reference when strategizing surgical interventions for Thai patients with spinal deformities.

Assessment of sleep patterns in dementia and general population cohorts using passive in-home monitoring technologies

BackgroundNocturnal disturbances are a common symptom experienced by People Living with Dementia (PLWD), and these often present prior to diagnosis. Whilst sleep anomalies have been frequently reported, most studies have been conducted in lab environments, which are expensive, invasive and not natural sleeping environments. In this study, we investigate the use of in-home nocturnal monitoring technologies, which enable passive data collection, at low cost, in real-world environments, and without requiring a change in routine.MethodsClustering analysis of passively collected sleep data in the natural sleep environment can help identify distinct sub-groups based on sleep patterns. The analysis uses sleep activity data from; (1) the Minder study, collecting in-home data from PLWD and (2) a general population dataset (combined n = 100, >9500 person-nights).ResultsUnsupervised clustering and profiling analysis identifies three distinct clusters. One cluster is predominantly PLWD relative to the two other groups (72% ± 3.22, p = 6.4 × 10−7, p = 1.2 × 10−2) and has the highest mean age (77.96 ± 0.93, p = 6.8 × 10−4 and p = 6.4 × 10−7). This cluster is defined by increases in light and wake after sleep onset (p = 1.5 × 10−22, p = 1.4 × 10−7 and p = 1.7 × 10−22, p = 1.4 × 10−23) and decreases in rapid eye movement (p = 5.5 × 10−12, p = 5.9 × 10−7) and non-rapid eye movement sleep duration (p = 1.7 × 10−4, p = 3.8 × 10−11), in comparison to the general population.ConclusionsIn line with current clinical knowledge, these results suggest detectable dementia sleep phenotypes, highlighting the potential for using passive digital technologies in PLWD, and for detecting architectural sleep changes more generally. This study indicates the feasibility of leveraging passive in-home technologies for disease monitoring.

The Association Between Solid Fuel Use and Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia in Sichuan, China: Cross-Sectional Study.

Benign prostatic hyperplasia (BPH) is a global age-related disease. It has been reported that over half of the Chinese male population aged 70 years or older are experiencing BPH. Solid fuel, which is the major source of household air pollution, has been reportedly associated with several adverse events, including sex hormone disorders. Due to the certain relationship between sex hormone levels and prostate disease, the relationship between solid fuel use and lower urinary tract symptoms (LUTSs) suggestive of BPH (LUTS/BPH) deserves further exploration. This study mainly aimed to investigate the association between solid fuel use and LUTS/BPH. The data used in this study were obtained from the West China Natural Population Cohort Study. Household energy sources were assessed using questionnaires. LUTS/BPH was evaluated based on participant self-reports. We performed propensity score matching (PSM) to reduce the influence of bias and unmeasured confounders. The odds ratio (OR) and 95% CI of LUTS/BPH for the solid fuel group compared with the clean fuel group were calculated. We also conducted stratified analyses based on BMI, metabolic syndrome, waist to hip ratio, drinking status, smoking status, and age. A total of 5463 participants were included in this study, including 399 solid fuel users and 5064 clean fuel users. After PSM, the solid fuel group included 354 participants, while the clean fuel group included 701 participants. Solid fuel use was positively correlated with LUTS/BPH before and after PSM (OR 1.68, 95% CI 1.31-2.15 and OR 1.81, 95% CI 1.35-2.44, respectively). In stratified analyses, the OR of the nonsmoking group was higher than that of the smoking group (OR 2.56, 95% CI 1.56-4.20 and OR 1.47, 95% CI 0.99-2.18, respectively). Similarly, the OR of the nondrinking group was higher than that of the drinking group (OR 2.70, 95% CI 1.46-4.99 and OR 1.48, 95% CI 1.01-2.17, respectively). A positive correlation between solid fuel use and LUTS/BPH was observed. The results suggest that improving fuel structure for household cooking and other household needs can possibly help reduce the risk of LUTS/BPH.

Initial Evaluation of Acceptability, Engagement, and Effectiveness of the MO App to Provide Tailored and Comprehensive Support for Smoking Cessation: Development and Usability Study.

Despite the growing availability of smoking cessation apps, low engagement and cessation rates have remained a significant challenge. To address this issue, we used a user-centered design to iteratively develop a mobile app (MO) to provide comprehensive, tailored, and evidence-based content to support smokers in their quitting journey. This study examined the acceptability, use, and preliminary efficacy of the MO app for smoking cessation. Specifically, we sought to understand smokers' preferred features, engagement, and satisfaction with MO; identify concerns in using the app and ways to improve the app; and evaluate its smoking cessation outcomes. Through 3 cohorts, we recruited 10, 12, and 85 adult smokers who attempted to quit smoking to pilot-test the MO app between December 2019 and July 2022. Participants were instructed to complete a baseline survey, interact with the app for 6 weeks, and fill in a postsurvey at week 6. Participants in cohort 3 completed an additional postsurvey at week 12. Participants' app use was tracked and analyzed. The primary outcome measures were participants' 7-day point prevalence abstinence at 6 and 12 weeks. Participants reported high levels of satisfaction with the MO app across all 3 cohorts, rating it between 4.40 and 4.76 on a scale of 5 for acceptability. Users engaged with app activities for an average of 89 to 159 times over 35 days. The most liked features of the app included "quit plan," "tracking," "reminders and notifications," "MOtalks," and "motivational quotes." The 7-day point prevalence abstinence rate of the modified intention to treat population in cohort 3 was 58% at 6 weeks and 52% at 12 weeks. Those who interacted more frequently with app features and engaged with more diverse activities were more likely to maintain abstinence at weeks 6 and 12. For each additional time logged into the app, the odds of staying abstinent at week 12 increased by 5% (odds ratio [OR] 1.05, 95% CI 1.01-1.08). Participants who earned >5000 points during app use also had higher odds of quitting at both 6 weeks (OR 3.12, 95% CI 1.25-7.75) and 12 weeks (OR 4.65, 95% CI 1.83-11.76), compared with those who earned <5000 points. Our study demonstrated that MO is a feasible mobile phone app with high acceptability and usability and can effectively deliver smoking cessation support to individuals who want to quit. Implications for developing and evaluating mobile phone apps for smoking cessation are discussed.

Association Between Gravidity and Anemia in Tabari Cohort Population: A Case-Control Study

Association Between Gravidity and Anemia in Tabari Cohort Population: A Case-Control Study

BELCOHORT: towards a population-based cohort for health research and policy support in Belgium

Abstract Background In the past decades much progress has been made in Belgium in the development and valorisation of population-based data collections which are directly or indirectly related to health. New surveys have been set up and the use of medico-administrative and environmental data for public health research gained momentum. However, no infrastructure is currently in place to link survey data with existing sources in a longitudinal perspective to address research questions directly relevant to health policy. BELCOHORT is a three-year pilot project aimed at developing a population based cohort enriched with these different data sources. The project is considered as a step towards a large population cohort in Belgium. Methods A first wave of participant recruitment was organized in February 2024 using the Belgian national register as a sampling frame, and 41,153 households were invited (targeted sample of 5000 individuals aged 18-69). A first baseline survey (online and paper) was organized and an annual follow-up is planned. Linkages procedures will be implemented with administrative data and geospatial data on air pollution and green space. The inclusion of data from physical examinations and biological samples will be explored. Results In the first recruitment wave the individual response rate was only 2.5%, leading to a sample of 1,947 participants. The sample showed an under-representation of women (45%), people aged 18-24 years (2%) and low educated people (21%). In total, 23% of participants opted to complete the first baseline questionnaire on paper. Stakeholder meetings have been started to implement the individual and geospatial linkages. Conclusions This project generate insights that will assist in methodological choices in the development of a large population cohort in Belgium. In the second recruitment lessons learned from the first data collection will be used to improve the response rate as well as the participation of under-represented groups. Key messages • This study provides insights on how existing population-based data collections including administrative and environmental data can be valorized in setting up a population cohort. • Recruitment strategies for a population cohort should be tested thoroughly and adapted in order to obtain a well-balanced sample composition.

Is there an association of anthracyclines with HFrEF and/or HFpEF in patients treated for breast cancer or lymphoma after 30 years of follow-up? Insights from the Rochester epidemiology project

Abstract Introduction Anthracyclines (ACs) have been identified as cardiotoxic drugs. They are associated with contractile dysfunction of the heart, which can manifest as heart failure. However, differentiating between HFrEF (left ventricular ejection fractions [LVEF] ≤40%) or HFpEF (LVEF &amp;gt;40%) has been overlooked. Purpose Using a retrospective cohort of patients with breast cancer (BC), Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and controls from the Rochester Epidemiology Project, we evaluated the association of ACs use with risk of HFrEF and/or HFpEF. Methods 797 subjects with BC, HL or NHL diagnosed from 1988 to 2010 were identified, 658 treated with ACs (ACs group) and 139 not treated with ACs (no-ACs group). Controls (n=1526) were subjects without cancer. The median (Q1, Q3) follow up was 11.5 years (7.4, 16.7). Cox proportional hazards regression was used to compare the risk of HFpEF and HFrEF in the three cohorts, adjustment for sex, CV comorbidities (type 2 diabetes [T2D], hypertension [HTN] and dyslipidemia), radiotherapy (RT), and ACs cumulative dose was performed. Results Baseline characteristics are shown in table 1. HFpEF occurred in 29/1526 subjects in the control group, 3/139 in the no-ACs group and in 14/658 in the ACs group. Compared to the control group, there was not an increased risk of developing HFpEF in the no-ACs group (HR 1.67, CI 95%: 0.5 – 5.53, p = 0.39) or in the ACs group (HR 1.83, CI 95%: 0.95 – 3.52, p = 0.06) (Figure 1). Compared with no-ACs group, the ACs group had a similar risk of developing HFpEF (HR 1.09, CI 95%: 0.3 – 3.87, p = 0.88). RT was associated with a lower risk of HFpEF (HR 0.21, CI 95%: 0.06 – 0.75, p = 0.01). In the multivariable analysis, T2D (HR 6.91, CI 95%: 3.07-15.56, p = &amp;lt;0.0001) was associated with higher risk of HFpEF. A cumulative dose of ACs &amp;gt; 250 mg/m2 was not associated with increased risk of HFpEF. HFrEF occurred in 25/1526 subjects in the control group, in 4/139 in the no-ACs group and in 31/658 in the ACs group. Compared to the control group, the ACs group had a significant increase in the risk of HFrEF (HR 4.77, CI 95%: 2.76 – 8.22, p &amp;lt; 0.0001), the no-ACs group did not (HR 2.81, CI 95%: 0.97 – 8.12, p = 0.055) (figure 2). RT was associated with lower risk of HFrEF (HR 0.29, CI 95%: 0.13 – 0.65, p = 0.002). In the multivariable analysis, ACs (HR 4.23, CI 95%: 2.4-7.47, p = &amp;lt; 0.0001) being male (HR 2.45, CI 95%: 1.43 – 4.15, p &amp;lt; 0.0001), smoking history (HR 2, CI 95%: 1.16 – 3.44, p &amp;lt; 0.01), and HTN (HR 3.23, CI 95%: 1.9 – 5.61, p &amp;lt; 0.0001), were associated with higher risk of HFrEF. A cumulative dose of ACs &amp;gt; 250 mg/m2 was not associated with increased risk of HFrEF. Conclusion To our knowledge this is the first study to differentiate between HFpEF and HFrEF in this cohort. ACs were not associated with increased risk of HFpEF. However, ACs were associated with increased risk of HFrEF, but not with a specific dose. These results should be validated in other population cohorts.

Clinical characteristics and outcomes of patients presenting with acute coronary syndromes and suspected plaque erosion

Abstract Background Plaque erosion (PE) is the second most common pathology of acute coronary events after plaque rupture. PE is characterized by endothelial denudation and formation of neutrophil extracellular traps. Patients with PE may have a different prognosis as compared to those with plaque rupture. Specific clinical and laboratory predictors were validated to suspect PE among acute coronary syndrome (ACS) patients. Purpose The objectives of this study were to compare both clinical and laboratory findings, and outcomes of ACS patients with high probability of PE and those with less likely PE. Methods Six hundred ninety-six ACS patients were divided into two groups (suspected PE vs less likely PE) based on 5 reported predictors of PE. The predictors were: age &amp;lt;68, anterior ischemia, no diabetes mellitus, hemoglobin &amp;gt;15 g/dL and normal renal function (eGFR&amp;gt; 60 ml/min) as assessed at hospital admission. Patients with 4 or 5 of these 5 predictors were included in the suspected PE group, while patients with 0 or 1 entered less likely PE group. Baseline clinical features and laboratory analyses at hospital admission were compared between the two groups. Major adverse cardiac events (MACE), defined as death from any cause, non-fatal myocardial infarction or unplanned revascularization, were compared between the two groups at 20 months after hospital discharge. Results Among 696 patients, 283 (41%) composed the suspected PE group, while 413 (59%) entered into less likely PE group. The suspected PE group had a higher prevalence of current smokers and had a higher BMI. They showed higher values of both LDL cholesterol and triglycerides, while C-reactive protein and fibrinogen levels were significantly lower. The suspected PE group showed a higher frequency of single vessel disease (Table). The suspected PE group showed a significantly lower rate of MACEs at 20 months (7.4% vs 28.8%, p=0.0001) as well as death from any cause was significantly lower (2.1% vs 24.9%, p=0.0001). The median time from the index ACS episode to recurrent myocardial infarction or unplanned coronary revascularization tended to be longer in the suspected PE group as compared to the less likely PE group (15 months [9-20] vs 9 months [6-13], p=0.062) (Figure). Conclusions In a cohort of ACS population, the suspected PE group showed distinctive clinical characteristics with less coronary plaque burden and low grade of systemic inflammation. The suspected PE group had a better prognosis at 20-month follow-up time with a significantly lower rate of death from any cause, and non-fatal coronary events tended to occur later.Table.Baseline characteristicsFigure.Non fatal coronary events

Reasons for Hospital Admission in Individuals With Multiple Sclerosis.

Health care utilization is higher in individuals with multiple sclerosis (MS) than in the general population. However, there are limited data on the reasons for their hospital admissions. Our primary objective is to analyze the reasons for the hospitalization of individuals with MS with the goal of identifying preventable causes. We conducted a retrospective analysis of a cohort of adults with a confirmed diagnosis of MS admitted to Duke University Hospital between January 2018 and January 2020. This yielded a cohort of 210 individuals. Data were analyzed using descriptive statistics. The most common reason for admission was urinary tract infection (UTI; 10.3%). The average length of stay was 6.1 days for the individuals with MS vs 5.5 days for the general population. The 30-day readmission rates were 14.9% and 15.5%, respectively. A significant number of admitted patients were not on any disease-modifying therapy (DMT), and no difference in median age was identified between those with a DMT vs those without. Length of stay and readmission rates were similar to those of the general population in this contemporary cohort. Given the prevalence of bladder dysfunction in MS, it is not surprising that a UTI was the most common reason for admission. Actively addressing management of and techniques for bladder dysfunction may decrease the admission rate for individuals with MS. Though we now have more treatment options for MS, many individuals with the highest health care utilization are not on a DMT. Future research is needed to identify the factors that can be addressed to support these patients and reduce preventable hospitalizations.

All-cause, cancer and cardiovascular mortality among South Asians living in the UK: Follow-up of the London Life Sciences Population (LOLIPOP) cohort

Abstract Background Although South Asians are the largest ethnic minority group in the UK, and the largest ethnic group worldwide, few studies have investigated patterns of mortality in South Asians. Methods We investigated 16,391 South Asian and 6,970 European men and women living in the UK, and participating in the London Life Sciences Prospective Population study. Participants were recruited in 2002-2008, and survival determined to 2019. We examined relationships of clinical, anthropometric, and lifestyle risk factors to mortality outcomes. Findings: Compared to Europeans, South Asians had higher prevalence of diabetes, cardiovascular disease, and hypertension, higher waist-hip ratio, fasting glucose, insulin and triglycerides, but lower smoking rates and HDL cholesterol (all P&amp;lt;0.001). Age and sex adjusted all-cause mortality was lower (Hazard Ratio (HR): 0.75 [0.68-0.81], P&amp;lt;0.001), all-cancer mortality was lower (HR 0.50 [0.43-0.58], P&amp;lt;0.001), and coronary heart disease (CHD) mortality was higher (HR 1.29 [1.05-1.60], P&amp;lt;0.01) in South Asians compared to Europeans. Mortality rates were ~50% lower for 9 of the 10 most common cancers in South Asians. After adjusting for risk factors, ethnic differences were attenuated only for CHD mortality. Interpretation: All-cause and cancer mortality are lower, but CHD mortality is higher, in South Asians compared to Europeans. Measured risk factors do not explain lower all-cause and all-cancer mortality, but do account for higher CHD mortality. Our findings provide evidence for population-specific exposures protective against cancers in South Asians, as well as the motivation to further improve cardiovascular risk reduction in this major ethnic group.

Associations of smoking status with long-term cardiovascular events in different arterial territories: the EPIC Norfolk prospective population cohort

Abstract Background Smoking cessation is associated with a reduced risk of cardiovascular disease (CVD) events, mainly in ischemic heart disease (IHD) and stroke. However, the impact of smoking status (never, former or current smoking) on long-term CVD events across different arterial territories remains understudied. Knowledge of such associations is important, as it may assist in risk communication and smoking cessation motivation. We therefore investigated associations between smoking status and territory-specific CVD events in a large cohort with ≥20 years follow-up. Methods We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between smoking, former smoking and never smoking with the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisation or death due to IHD, ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, systolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), diabetes, renal function and body mass index. We compared former and current smoking (at baseline) with never smoking. Results We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. Current (vs. never) smoking was associated with IHD [adjusted hazard rate (aHR) 1.53, 95% confidence interval (CI) 1.36-1.72], PAD (aHR 1.29, 95%CI 1.07-1.56) and AA (aHR 4.81, 95%CI 3.54-6.54). Current smoking was not significantly associated with ischemic stroke (aHR 1.20, 95% CI 0.95-1.52) and haemorrhagic stroke (aHR 1.18, 95% CI 0.81-1.70). In former (vs. never) smoking individuals, the association with AA remained statistically significant but less pronounced [aHR 1.69, 95%CI 1.29-2.23]. Conversely, former smoking was not associated with IHD (aHR 1.07, 95%CI 0.99-1.16) or PAD (aHR 1.09, 95%CI 0.95-1.26) (Figure 1). Conclusion After 20-years of follow-up, former smokers, compared to never-smokers, remain at considerably higher risk for CVD events, particularly for aortic aneurysm. This knowledge may assist in treatment decisions and risk communication.

Validation of existing risk scores for worsening renal function in patients with newly diagnosed heart failure: a longitudinal population cohort study

Abstract Background Worsening renal function (WRF) is one of the strongest predictors of outcome in patients with heart failure (HF). The presence of WRF often influences the decision to start, up-titrate, or discontinue disease-modifying HF therapies and is one of the key determinants of suboptimal guideline-directed medical therapy. However, there are now potential cardiovascular pharmacotherapies that have favourable cardiorenal outcomes and reduce the risk of renal decline. It is therefore important to identify patients with HF early in their disease trajectory who are at risk of developing WRF. Purpose The aim of this study was to evaluate two existing WRF risk scores (the Forman risk score and the Basel risk score) in a population-based longitudinal cohort diagnosed with incident HF. Methods Data for individuals with incident HF between 2016 to 2021 were extracted and analysed from the NELSON study conducted in Tayside, Scotland. WRF was defined as a composite event of (i) having two consecutive eGFRs declined by 40% or greater; (ii) having an eGFR &amp;lt; 15mL/min/1.73m2; (iii) initiation of sustained dialysis; (iv) development of end-stage kidney disease; or (v) receiving kidney transplantation. The primary outcome was the occurrence of WRF within 180 days of diagnosis of HF. Among patients hospitalised with HF, in-hospital WRF was also assessed. The area under the curve (AUC) was used to assess the discrimination performance of the two risk scores in individuals with incident HF diagnosed as either in-patients or out-patients. Results 4076 individuals (mean age 72.8 ± 13.2; 58% male; 1081 HFrEF, 646 HFmrEF, 1348 HFpEF, and 1001 HF with unknown ejection fraction (EF)) who were WRF-free at incident HF diagnosis were identified. Of these, 2095 (51.4%) were diagnosed as in-patients, and 1981 (48.6%) were diagnosed as out-patients. 285 (7%) patients developed WRF within 180 days post HF diagnosis. Among the 2,095 HF in-patients, 75 (3.6%) developed WRF before discharge. The Forman risk score had an AUC of 0.618 (95% CI: 0.585 – 0.651) in predicting 180-day WRF, and an AUC of 0.650 (0.587 – 0.713) for in-hospital WRF. The Basel risk score showed similar discriminating performance with an AUC of 0.618 (0.585 – 0.651) for 180-day WRF, and 0.656 (0.593 – 0.719) for in hospital WRF. Conclusions In a contemporary population, conventional risk scores such as the Forman or Basel risk scores have limited discrimination in predicting WRF in incident HF. New models with better discrimination for WRF prediction are therefore needed.

The impact of multimorbidity on cardiac remodelling in the UK Biobank

Abstract Background/Introduction Previous work has suggested that multimorbidity is associated with higher all-cause mortality and cardiovascular mortality in the UK Biobank (UKB). The impact of multimorbidity on cardiac remodelling as measured by cardiovascular magnetic resonance (CMR) has not been studied in large cohorts. Purpose To determine if CMR biomarkers act as surrogates for adverse cardiovascular outcomes in multimorbidity. Method We analysed 44957 UKB participants who had CMR. Self-reported cancer (UKB field ID 20001) and non-cancer illnesses (UKB field ID 20002) were used to calculate comorbidity count with multi-morbidity defined as 2 or more illnesses. The predictive value of comorbidity count (exposure counts measured in quintiles) on CMR traits (outcomes) was evaluated using a univariable and multivariable generalised linear model. Covariates included sex, age, BMI, smoking status, regular alcohol intake, and the Townsend deprivation index, a measure of socioeconomic deprivation. The first model utilised univariable regression without covariates with subsequent iterations including age and sex and then all covariates. An interaction term was included for age and sex and a quadratic term for age in the models. CMR outcome measures were indexed left ventricular mass (LVM), indexed left ventricular end diastolic volume (LVEDV), indexed left ventricular end systolic volume (LVESV), indexed left ventricular stroke volume (LVSV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and indexed maximal left atrial volume (LA). The absolute value of GLS was used in the regression models. Variance inflation factor testing was used to check for collinearity. Analyses were completed using R v4.1.1. Results Median comorbidity count was 2. The burden of long-term conditions in this population of European ancestry with largely healthy individuals is lower than in other large population cohorts. Table 1 summarises multivariable analyses for comorbidity count, LVM and GLS. Due to high collinearity relating to age in the model, we centred age around the mean. LVM was higher with multimorbidity (top quintile Beta 0.63 (95% CI 0.23 to 1.04), P = 2.21x10-03). GLS was lower with multimorbidity (top quintile Beta -0.29 (95%CI -0.42 to 0.16), P = 8.10x10-6). LA volume was lower with multimorbidity (top quintile Beta -0.63(95% CI -1.22 to 0.04), P = 3.53 x 10-2). LVEF and other volume measures were not associated with multimorbidity. Conclusion Multimorbidity in this large cohort was associated with adverse cardiac structural and functional remodelling on CMR. These include a lower global longitudinal strain and higher LV mass.

Multivariate time-series clustering of cardiopulmonary exercise test data for cardiovascular risk stratification

Abstract Aims Current clinical practice assesses cardiorespiratory fitness (CRF) by evaluating summary indexes of cardiopulmonary exercise tests (CPET). Yet, the raw time series recordings may hold additional information with clinical relevance. In this study, we investigated if the interpretation of raw CPET data could identify distinct CRF phenogroups and improve risk stratification. Methods In 1399 participants (mean age, 56.4 years; 37.7% women), who underwent maximal CPET by cycle ergometer, we collected baseline clinical characteristics and information on incident cardiovascular (CV) events (n=297) on average 4.3 years later. We employed dynamic time warping combined with k-medoids to identify phenogroups from raw CPET time-series. To evaluate the clinical significance of the derived phenogroups we compared clinical characteristics and incidence of CV events, while an external population cohort (n=171) was used to further validate the trained model. Results The optimal number of clusters was 5. We observed significant differences in age, use of medication, spirometry indexes and disease prevalence across all clusters. Cluster 5 was associated with the worst CV profile with higher use of antihypertensive medication and history of CV disease while cluster 1 represented the most favourable risk profile. After adjusting for traditional clinical covariables, clusters 4 (HR: 1.30; 95%CI: 1.02-1.65; p=0.033) and 5 (HR: 1.36; 95%CI: 1.08-1.72; p=0.0088) had significantly higher risk for incident CV events compared to clusters 1 and 2. Comparing clinical characteristics across clusters in the external validation cohort revealed similar patterns. Conclusion – Employing unsupervised machine learning on time series CPET recordings, we identified clinically meaningful CRF phenogroups. An integrative CRF profiling might facilitate CV risk stratification and consequently risk management.

Temporal trends in major bleeding after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction from 2003 to 2017: the Western Denmark Heart Registry

Abstract Background Management of patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) has changed during the last two decades. Introduction of more potent platelet inhibitors may carry an increased risk of bleeding complications, while other therapeutic options, such as use of radial artery access and proton pump inhibitors may reduce bleeding risk. The combined impact of these treatment changes on bleeding risk in patients with STEMI remains unknown. Purpose To examine temporal trends in 1-year risk of major bleeding after STEMI treated with primary PCI from 2003 to 2017. Methods We used the Western Denmark Heart Registry to identify first-time PCI-treated patients undergoing primary PCI for STEMI from 2003 to 2017. Patients were divided into 4 calendar periods based on the time of STEMI. The main outcome was 1-year risk of major bleeding defined as a hospital admission for bleeding using a validated definition with high accuracy. Additionally, the 1-year risk of major bleeding in STEMI patients was compared with the risk in an age- and sex-matched general population cohort without prior coronary artery disease. Results From 2003 to 2017, we identified 18,540 patients treated with primary PCI for STEMI (median age 64 years, 75% men)and 92,700 age- and sex-matched individuals. The 1-year risk of major bleeding after STEMI was similar across the different time periods; 4.1% in 2003-2006, 3.8% in 2007-2010, 3.8% in 2011-2014, and 4.5% in 2015-2017. The adjusted HR for bleeding in STEMI patients was 1.03 (95% CI 0.83-1.26) when comparing the latest period with the earliest period. The age- and sex-matched general population exhibited a 1-year risk of major bleeding of around 1% in all time periods (Figure 1). Conclusions Despite changes in management, the 1-year risk of major bleeding remained stable around 4% after primary PCI-treated STEMI from 2003 to 2017. This risk was approximately 4 times higher than the bleeding risk observed in an age- and sex-matched general population.

Symptomatic patients without coronary artery disease do not have excess cardiovascular risk compared to the general population

Abstract Background Patients with stable angina with no coronary atherosclerosis by coronary computed tomography angiography (CCTA) have a lower cardiovascular risk compared to CCTA patients with greater atherosclerotic burden. However, it remains unknown whether these symptomatic patients have excess cardiovascular risk when compared to the general population and if any excess risk is sex or age dependent. Purpose To examine the 10-year cardiovascular risk and mortality in patients with no coronary atherosclerosis by CCTA compared to a matched general population comparison cohort. Methods We included every symptomatic CCTA patient with no coronary artery disease (CAD), defined as no coronary plaques and Agatston calcium score of 0, in Western Denmark from 2008-2021. Each patient was matched by age and sex with 5 individuals with no previous history of ischemic heart disease from the Western Danish general population. Maximum follow-up was 10 years. Outcomes were myocardial infarction, ischemic stroke, and all-cause death. We estimated 10-year risk difference (RD) and incidence rate ratios (IRR) using a conditional Poisson regression, comparing patients with no CAD to the general population cohort. Additionally, we performed age- (&amp;lt;45 year, 45-65 years, and ≥65 years) and sex stratified analyses. Results We included 39,223 patients with no CAD who were matched with 196,115 individuals from the general population. Median age was 54 and 60% were women. Baseline use of anti-thrombotic agents, statins, and anti-hypertensive drugs was higher in patients with no CAD than the general population. Median follow-up was 6.1 years. CCTA patients with no CAD had lower risk of myocardial infarction [RD -0.2%, IRR 0.75 (95% CI 0.65-0.85)] and death [RD -3.3%, IRR 0.51 (95% CI 0.48-0.55)], but similar risk of ischemic stroke [RD 0.0%, IRR 0.93 (95% CI 0.84-1.02)] compared to the general population (Figure 1). However, patients &amp;lt;45 years had higher 10-year risk of both myocardial infarction and ischemic stroke despite absence of CAD by CCTA compared the general population (Figure 2). Conclusions Symptomatic patients without CAD by CCTA do not have excess cardiovascular risk when compared to a general population cohort without known ischemic heart disease. Future cardiovascular risk management of these patients should therefore follow primary prevention guidelines. However, patients &amp;lt;45 years did exhibit higher risk of ischemic outcomes and may require intensified preventative treatment.Figure 1Figure 2

Time-series clustering of raw recordings of 24-hour ambulatory blood presssure for risk stratification in general population

Abstract Objective 24-hour ambulatory blood pressure measurements (ABPM) is the best out-of-office BP measurement used to refine cardiovascular (CV) risk stratification. Currently, only summary ABPM indexes are used in the clinical practice while the temporal characteristics of the raw BP recordings have not been explored. Therefore, in this study we employed an unsupervised machine learning (ML) algorithm suitable for multivariate time-series analysis to identify distinct BP and heart rate (HR) profiles associated with the incidence of adverse CV events. Design and Method In 1391 community-dwelling individuals (mean age, 46.9 years; 50.97% women), we acquired 24-hour ABPM and clinical data and collected CV events (n=399) on average 22 years later. We employed multivariate dynamic time warping and k-medoids algorithm on the raw recordings of systolic and diastolic BP and HR. To assess the clinical significance of the derived clusters, we compared the clinical characteristics and the incidence of adverse events. We validated the trained model using 24-hour ABPM obtained from external population cohort (n=1137). Results The silhouette score and Dunn index showed that the optimal number of clusters was 4. Across all clusters we observed significant difference in age and sex distribution. Cluster 4 had the worst CV risk factors profiling, with higher office BP and anti-hypertensive medication intake compared to the other clusters. We observed differences in the incidence of adverse events between clusters (Figure), with cluster 1 representing the lowest risk group and cluster 4 the highest. After adjusting for traditional CV risk factors, including office systolic BP, cluster 1 had the lowest risk (HR:0.92; 95%CI:0.84-0.99; P=0.036) and cluster 4 the highest (HR:1.13; 95%CI:1.03-1.24; P=0.006) as compared to the average population risk. The analysis of the external validation cohort revealed similar ABPM patterns and clinical characteristics. Conclusion Employing an unsupervised ML model on the raw ABPM recordings we identified clinically meaningful clusters associated with an increasing cumulative incidence of CV events. This ML analysis paves the way towards utilization of temporal BP and HR information and subsequently optimization of CV risk stratification.

Deep learning for fully automated echocardiographic measurements of left ventricular wall thickness and chamber dimensions in the parasternal long-axis view

Abstract Background Accurate quantification of left ventricular (LV) wall thickness and chamber dimensions in the echocardiographic parasternal long-axis view (PLAX) is crucial for clinical decisions in patients with heart disease. However, there is a need for more reproducible and time-efficient methods. Fully automated deep learning (DL)-based methods could address this need. Purpose To develop a DL-based method for fully automated measurements of LV wall thickness and chamber dimensions in PLAX, validate its performance in a large population cohort, and evaluate its capacity to differentiate between hypertensive and normotensive groups. Methods DL networks were trained on PLAX recordings from 207 subjects. The DL method performed cardiac segmentation, timing of end-systole and end-diastole, and measured LV wall thickness and chamber dimensions in PLAX. The model was validated in a large populational echocardiography dataset including a subset with test-retest evaluation. Agreement with expert reference measurements, test-retest reproducibility, and comparison of normotensive and hypertensive (defined as those on hypertensive medication or with systolic blood pressure &amp;gt;160 mmHg) groups were evaluated. Results In the populational study of 2047 subjects, the novel DL method demonstrated a feasibility of 97.6%. Strong agreement was observed between the automated DL method and expert readers in measuring end-diastolic septal thickness, posterior wall thickness, and LV diameter (bias 0.1 mm, 0.2 mm, and 2.2 mm, respectively, Figure 1). In a test-retest dataset (n=40, with 2 recordings per patient and 4 readers), the novel DL method displayed improved reproducibility compared to inter-reader measurements, with minimal detectable change for interventricular septal diameter 2.2 mm versus 2.6 mm, posterior wall diameter 1.2 mm versus 2.5 mm, and LV diameter 5.0 mm versus 6.3 mm (Figure 2). The DL method measured significantly wider septal diameter in the hypertensive group compared to normotensive group (p&amp;lt;0.001). Mean analysis time for wall thickness and chamber dimensions using the DL method was 1.2 seconds. Conclusion The novel DL method accurately measured LV wall thickness and chamber dimensions in the PLAX view, and demonstrated improved test-retest reproducibility compared to experienced echocardiographers. Additionally, it was able to detect significantly wider septal diameters in the hypertensive population. By providing fast and reliable measurements in retrospective data, and with potential for real-time measurements during image acquisition, this DL method has the potential to improve the yield, efficiency, and workflow in echocardiography.Bland-Altman posterior wall diameterTest-retest posterior wall diameter

Epicardial adipose tissue and subclinical alterations in cardiac structure and function in early adulthood

Abstract Background Epicardial adipose tissue (EAT) is the visceral fat depot surrounding the heart and coronary arteries and shares the same microcirculation with myocardium. Under normal physiologic conditions EAT contains important cardioprotective properties such as cushioning the heart against mechanical stress, thermoregulation of the myocardium in hypothermia as well as balancing myocardial fatty acid homeostasis. Higher accumulation of EAT has been reported to independently associate with deleterious alterations in cardiac structure and function. However, majority of previously addressed study results are derived from older study population and in presence of cardiovascular diseases. Data on the associations of EAT and cardiac echocardiograpghically derived structural and functional parameters in a young and middle-aged population without prevalent cardiovascular disease is scarce. Purpose We aimed to address this knowledge gap by investigating the associations of echocardiographically measured EAT thickness and possible adverse subclinical alteration in cardiac structure and function in a population cohort of young and middle-aged adults. Methods This study participants were examined as part of the ongoing multi-centre longitudinal cohort, focusing on cardiovascular risk factors from childhood through adulthood. EAT thickness was measured by manual delineation from parasternal long-axis echocardiograms at end systole. Transthoracic and Doppler echocardiograpghy was performed and data on cardiac structural and functional parameters were derived comprehensively in accordance with EAE/ASE guidelines. Results In this study population (N=1677, men=770, women=897 ; age range 34-49 years) mean EAT thickness was 4.0 mm in whole population. In multivariable regression analysis models adjusted for age, sex, waist circumference and systolic blood pressure, significant independent associations of EAT and left atrial dimension (P&amp;lt;.0001) and various measures of left ventricular (LV) wall thickness such as LV mean wall thickness (P&amp;lt;.001), LV relative wall thickness (P&amp;lt;.001) as well as LV posterior wall thickness (P&amp;lt;.001) were observed. We found no significant associations between EAT thickness and cardiac functional and hemodynamic parameters after covariate adjustments in multivariable analysis models. Conclusion The findings of this study highlight that larger EAT thickness is associated with subclinical alteration in cardiac wall thicknesses in young and middle-aged adults. However, we found no associations between EAT thickness and cardiac functional parameters, which is perhaps due to the high cardiac adaptation properties in our relatively young study population. Therefore, further follow-ups is required to address long-term probable alterations in cardiac hemodynamics when the participants are older.

Lipoprotein(a) levels and LPA genotypes are not associated with echocardiographic measures of left ventricular structure and function in the general population

Abstract Background Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for myocardial infarction and aortic valve stenosis, and elevated Lp(a) levels are associated with increased risk of heart failure. While part of this heart failure risk is mediated through atherosclerotic and valvular disease, other pathological pathways may also contribute to the association between Lp(a) and heart failure. Purpose To assess if Lp(a) levels and corresponding LPA genotypes are associated with echocardiographic measures of left ventricular structure and function in the general population. Methods We included 3,427 participants from an observational general population study who underwent protocol echocardiography between 2011-15 and had an available measurement of Lp(a) and LPA genotypes. Lp(a) was measured in 1991-94 and 2001-03 using well-validated assays with the most recent measurement used for the present analysis. Participants were divided into groups based on quartiles of Lp(a) with the top quartile further stratified to capture those above the 90th percentile. For genetic analysis, participants were grouped based on kringle IV type 2 [KIV-2] repeat corresponding to plasma Lp(a) percentile groups. Linear regression models were used to estimate β-coefficients for echocardiographic measures associated with Lp(a) levels and genotypes, while logistic regression models were used to estimate odds ratios for cardiac dysfunction or remodeling. All models were adjusted for age and sex. Results Mean age was 63±14 years and 44% were male. Median plasma Lp(a) was 18 mg/dL [IQR 10-40], median number of KIV-2 repeats were 36 [30-40], 102 (3%) were rs3798220 minor allele carriers and 467 (14%) were rs10455872 carriers. Mean left ventricular ejection fraction [LVEF] was 56.0±6.6% and we had 99% power to detect an absolute LVEF difference of 2% between those with Lp(a) levels above the 90th percentile (corresponding to &amp;gt;75 mg/dL) compared with those below the 25th percentile (&amp;lt;10 mg/dL). Mean absolute global longitudinal strain (GLS) was 19.2±2.7% and we had 99% power to detect an absolute difference of 1%. However, we found no statistically significant differences in echocardiographic measures according to Lp(a) levels or LPA genotypes (Table 1). The prevalence of impaired LVEF was 16%, and we had &amp;lt;20% power to detect an odds ratio of 1.2 for those with Lp(a) above the 90th percentile compared with those below the 25th percentile. We found no significant associations between odds for cardiac dysfunction or left ventricular hypertrophy and Lp(a) levels or LPA genotypes (Table 2). Conclusion Elevated Lp(a) levels and corresponding LPA genotypes were not associated with echocardiographic measures of left ventricular structure and function in this general population cohort. While we did not have sufficient power to detect associations between Lp(a) and cardiac dysfunction, our findings do not support a substantial effect of Lp(a).