Major Cardiovascular Disease Research Articles

Subclinical Hyperthyroidism and Cardiovascular Disease.

Background: In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. Summary: We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. SCHyper appears to have little association with stroke risk and has shown conflicting results regarding CHD risk. Regarding the degree of serum TSH suppression, evidence shows a higher risk of CVD in SCHyper individuals with suppressed TSH (<0.1 mIU/L) compared with those with low TSH (0.1-0.4 mIU/L). Despite evidence that older individuals are inherently at a higher risk for CVD, no studies have yet demonstrated an age-related increase in the relative risk of CVD in SCHyper. Conclusion: The studies indicate that SCHyper is associated with an increased risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. Considering the importance of the degree of serum TSH suppression and age as risk factors for CVD, treatment decisions should be individualized based on their specific risk factors.

Emerging EAT-Lancet planetary health diet is associated with major cardiovascular diseases and all-cause mortality: A global systematic review and meta-analysis

Background&AimsIn 2019, the EAT-Lancet Commission promoted a plant-based diet, emphasizing its potential to enhance human health and environmental sustainability. Nevertheless, a thorough evaluation of health benefits associated with EAT-Lancet diet requires robust statistical backing. This synthesis seeks to compile evidence related to the effects of the EAT-Lancet diet on major cardiovascular disease (CVD) and mortality. MethodsA systematic review and meta-analysis were conducted utilizing data from MEDLINE, EMBASE, PubMed, Web of Science, and medRxiv, covering the period from January 2019 to October 8, 2024. We included all cohort and case-control studies that investigated the association between the emerging EAT-Lancet diet and outcomes such as diabetes, CVD, all-cause mortality, and cancer. Summary effect size estimates are presented as hazard ratios (HRs) and were analyzed using random-effects models. Study heterogeneity was assessed with the Q statistic and I2 statistic. Subgroup analyses were performed to identify potential sources of variability, while publication bias was evaluated using Begg’s and Egger’s tests. Additionally, sensitivity analyses were conducted to assess the robustness of the results. ResultsWe identified 28 publications that included a total of over 2.21 million participants. Adhering to the EAT-Lancet dietary patterns was negatively associated with diabetes, CVD (mortality), all-cause mortality, and cancer (mortality), with HRs of 0.78 (95% CI: 0.65-0.92), 0.84 (95% CI: 0.81-0.87), 0.83 (95% CI: 0.78-0.89), and 0.86 (95% CI: 0.80-0.92), respectively. Significant heterogeneity was observed for diabetes (I2=94.0%), all-cause mortality (I2=85.5%), and cancer incidence (I2=79.3%). Importantly, no evidence of publication bias was found for any of the clinical outcomes analyzed. Sensitivity analyses confirmed the robustness of the results across various dietary scoring systems for CVD mortality, all-cause mortality, and cancer. ConclusionFollowing the EAT-Lancet diet was significantly associated with reduced odds of diabetes, CVD, cancer and mortality. These findings are clinically important, highlighting the beneficial effects of the recent EAT-Lancet diet on various health outcomes.

Cardiovascular risk factors and all-cause mortality in older age (15-year cohort study)

Cardiovascular diseases (CVD) occupy a leading position in the structure of all-cause mortality. Prospective and interventional studies have identified the major risk factors for CVD and shown their associations with the risk of cardiovascular outcomes and all-cause death. The impact on the individual risk of death may vary by age, sex, study design, and may be population-specific. We aimed to study the contribution of major CVD risk factors to the 15-year risk of all-cause death in the Russian (Siberian) population cohort aged 45–69 years.Material and methods. A random population sample (men and women 45–69 years old, n = 9360) was examined at baseline in 2003–2005 (Novosibirsk, Russian branch of the HAPIEE project) and re-examined twice in 2006–2008 and 2015–2018. Current analysis included individuals without baseline CVD (n = 8087), the average follow-up period – 15.6 (SD 0.69) years. The fatal events were registered based on death certificates from the Population Registration Bureau (ZAGS), and using the data received at serial examinations and postal interview. We analyzed the association between CVD risk factors and all-cause death using multivariate Cox regression.Results. In a cohort aged 45–69, in the adjusted model, 15-year risk of all-cause death was positively associated with age (HR = 1.08; 95 % CI 1.07–1.09), male sex (HR = 1.46; 95 % CI 1.24–1.71), hypertension (HT) (HR = 1.39; 95 % CI 1.25–1.55), smoking (HR = 2.37; 95 % CI 2.08–2.70), high WHR (HR = 1.19; 95 % CI 1.06–1.33), and type 2 diabetes (T2DM) (HR = 1.52; 95 % CI 1.34–1.73), and it was negatively associated with elevated total cholesterol (TC) or LDL-C in blood. In age- and sex-adjusted model, the risk was additionally associated with high triglycerides (HTG), obesity and elevated fasting plasma glucose (FPG). In men, the risk of death was independently associated with age, HT, smoking, low HDL-C, high WHR, and T2DM. In women, the risk of death was independently associated with age, HT, T2DM smoking, and, in age-standardized models, obesity, high WHR, and hyperglycemia.Conclusions. In a population cohort of 45 years and older, among CVD risk factors male sex, HT, smoking, central obesity, and T2DM independently contributed to the risk of all-cause death. Among lipid parameters, low HDL-C and high TG levels increased the risk of death in men. Associations between cardiovascular risk factors and the risk of all-cause death in older people have the patterns specific for older age; these features are important to take into account in a strategy to reduce mortality in the population.

Changes in 10-Year Predicted Cardiovascular Disease Risk for a Multiethnic Semirural Population in South East Asia: Prospective Study.

Cardiovascular disease (CVD) risk factors tend to cluster and interact multiplicatively and have been incorporated into risk equations such as the Framingham risk score, which can reasonably predict CVD over short- and long-term periods. Beyond risk factor levels at a single time point, recent evidence demonstrated that risk trajectories are differentially related to CVD risk. However, factors associated with suboptimal control or unstable CVD risk trajectories are not yet established. This study aims to examine factors associated with CVD risk trajectories in a semirural, multiethnic community-dwelling population. Data on demographic, socioeconomic, lifestyle, mental health, and cardiovascular factors were measured at baseline (2013) and during follow-up (2018) of the South East Asia Community Observatory cohort. The 10-year CVD risk change transition was computed. The trajectory patterns identified were improved; remained unchanged in low, moderate, or high CVD risk clusters; and worsened CVD risk trajectories. Multivariable regression analyses were used to examine the association between risk factors and changes in Framingham risk score and predicted CVD risk trajectory patterns with adjustments for concurrent risk factors. Of the 6599 multiethnic community-dwelling individuals (n=3954, 59.92% female participants and n=2645, 40.08% male participants; mean age 55.3, SD 10.6 years), CVD risk increased over time in 33.37% (n=2202) of the sample population, while 24.38% (n=1609 remained in the high-risk trajectory pattern, which was reflected by the increased prevalence of all major CVD risk factors over the 5-year follow-up. Meanwhile, sex-specific prevalence data indicate that 21.44% (n=567) of male and 41.35% (n=1635) of female participants experienced an increase in CVD risk. However, a stark sex difference was observed in those remaining in the high CVD risk cluster, with 45.1% (n=1193) male participants and 10.52% (n=416) female participants. Regarding specific CVD risk factors, male participants exhibited a higher percentage increase in the prevalence of hypertension, antihypertensive medication use, smoking, and obesity, while female participants showed a higher prevalence of diabetes. Further regression analyses identified that Malay compared to Chinese (P<.001) and Indian (P=.04) ethnicity, nonmarried status (P<.001), full-time employment (P<.001), and depressive symptoms (P=.04) were all significantly associated with increased CVD risk scores. In addition, lower educational levels and frequently having meals from outside were significantly associated to higher odds of both worsening and remaining in high CVD risk trajectories. Sociodemographics and mental health were found to be differently associated with CVD risk trajectories, warranting future research to disentangle the role of psychosocial disparities in CVD. Our findings carry public health implications, suggesting that the rise in major risk factors along with psychosocial disparities could potentially elevate CVD risk among individuals in underserved settings. More prevention efforts that continuously monitor CVD risk and consider changes in risk factors among vulnerable populations should be emphasized.

Adherence to cardiovascular medications and risk of cardiovascular disease in breast cancer patients: A causal inference approach in the Pathways Heart Study

Purpose Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005–2013. Methods Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA&lt;100% versus CAA = 100% (ref), 2) CAA&lt;80% versus CAA≥80% (ref) and 3) CAA&lt;80% versus 80%≤CAA&lt;100% versus CAA = 100%. Results Poor statin adherence (CAA&lt;80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA&lt;100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA&lt;80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD. Conclusions Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.

Well-Being and Cardiovascular Health: Insights From the UK Biobank Study.

Cardiovascular diseases (CVDs) are a leading global health concern. Emerging evidence suggests a potential protective role of well-being in reducing CVD risk. We conducted a cohort analysis using the UK Biobank data set, encompassing 121 317 participants. We assessed the well-being of participants using a well-being index derived from baseline questionnaires. Well-being categories were derived by latent class analysis using general happiness and satisfaction with family, friendships, health, and finance situations. The relationship between well-being and 4 major CVDs was analyzed using Cox proportional hazards models and Mendelian randomization. The study also examined the impacts of well-being on lifestyle factors and inflammatory markers, and its mediating role in the well-being-CVD relationship. Higher well-being was associated with a significantly reduced risk of various CVDs. Latent class analysis identified 4 distinct well-being groups (low, variable, moderate-to-high, and high satisfaction), with higher satisfaction levels generally associated with lower risk of CVDs. Mendelian randomization suggested potential causal relationships between well-being and reduced risk of CVDs. Participants with greater well-being demonstrated healthier behaviors and lower levels of inflammatory markers. Mediation analysis indicated that lifestyle and inflammatory markers partially mediated the relationship between well-being and CVDs. This study demonstrates a robust inverse association between well-being and the risks of CVDs, suggesting that enhancing well-being may be a viable strategy for CVD prevention. The role of lifestyle factors and inflammation as a mediator provides insight into possible biological pathways linking psychological states and cardiovascular health.

Artificial intelligence in cardiology: a peek at the future and the role of ChatGPT in cardiology practice.

Artificial intelligence has increasingly become an integral part of our daily activities. ChatGPT, a natural language processing technology developed by OpenAI, is widely used in various industries, including healthcare. The application of ChatGPT in healthcare is still evolving, with studies exploring its potential in clinical decision-making, patient education, workflow optimization, and scientific literature. ChatGPT could be exploited in the medical field to improve patient education and information, thus increasing compliance. ChatGPT could facilitate information exchange on major cardiovascular diseases, provide clinical decision support, and improve patient communication and education. It could assist the clinician in differential diagnosis, suggest appropriate imaging modalities, and optimize treatment plans based on evidence-based guidelines. However, it is unclear whether it will be possible to use ChatGPT for the management of patients who require rapid decisions. Indeed, many drawbacks are associated with the daily use of these technologies in the medical field, such as insufficient expertise in specialized fields and a lack of comprehension of the context in which it works. The pros and cons of its use have been explored in this review, which was not written with the help of ChatGPT.

Beyond lung cancer screening, an opportunity for early detection of chronic obstructive pulmonary disease and cardiovascular diseases.

Lung cancer screening programs concern smokers at risk for cardiovascular diseases (CVDs) and chronic obstructive pulmonary disease (COPD). The LUMASCAN (LUng Cancer Screening, MArkers and low-dose computed tomography SCANner) study aimed to evaluate the acceptability and feasibility of screening for these 3 diseases in a community population with centralized organization and to determine low-dose computed tomography (CT) markers associated with each disease. This cohort enrolled participants meeting National Comprehensive Cancer Network criteria (v1.2014) in an organized lung cancer-screening program including low-dose CT scans; spirometry; evaluations of coronary artery calcifications (CACs); and a smoking cessation plan at inclusion, 1, and 2 years; then telephone follow-up. Outcomes were the participation rate and the proportion of participants affected by lung cancer, obstructive lung disease, or CVD events. Logistic-regression models were used to identify radiological factors associated with each disease. Between 2016 and 2019, a total of 302 participants were enrolled: 61% men; median age 58.8 years; 77% active smoker; 11% diabetes; 38% hypertension; and 27% taking lipid-lowering agents. Inclusion, 1-year, and 2-year participation rates were 99%, 81%, 79%, respectively. After a median follow-up of 5.81 years, screenings detected 12 (4%) lung cancer, 9 of 12 via low-dose CT (78% localized) and 3 of 12 during follow-up (all stage IV), 83 (27%) unknown obstructive lung disease, and 131 (43.4%) moderate to severe CACs warranting a cardiology consultation. Preexisting COPD and moderate to severe CACs were associated with major CVD events with odds ratios of 1.98 (95% confident interval [CI] = 1.00 to 3.88) and 3.27 (95% CI = 1.72 to 6.43), respectively. The LUMASCAN study demonstrated the feasibility of combined screening for lung cancer, COPD, and CVD in a community population. Its centralized organization enabled high participation and coordination of healthcare practitioners.

P206 ANALYZING ATTRITION POINTS IN INDONESIA'S HYPERTENSION CARE CASCADE: STUDY OF 200,000 POPULATION FROM 2013-2018

Background: According to NCDRisC, Indonesia ranks as the worst performer globally in hypertension control, with control rates of 5.1% for females and 3.6% for males, despite having an income level with better potential outcomes. Hypertension is a leading risk factor for cardiovascular disease (CVD), and its management is critical for reducing major CVD risks. This study aims to identify the significant attrition points in the hypertension care cascade in Indonesia, focusing on identifying where the most significant drop-offs occur at each stage. Methods: The study utilizes data from the 2018 Indonesian Basic Health Research (RISKESDAS), a nationally representative health survey sample of ∼1 million individuals. The hypertension care cascade was divided into stages: prevalence, diagnosis, treatment, and control. Descriptive statistics and attrition analysis were used to analyze the data. Results: Indonesia managed to diagnose 29.6% of its hypertensive population and treat 23.4%, yet only 4.4% achieved control over their condition. Between 2013 and 2018, diagnosis rates slightly decreased from 33.5% to 29.6%, while treatment rates significantly improved, doubling from 10.7% to 23.4%. Control rates modestly improved by ∼60% from 2013 to 2018, from 2.6% to 4.4%. The diagnostic phase showed the highest attrition, with over 70% of the hypertensive population undiagnosed. Improvement in diagnosed-to-treated performance was observed, with conversion rates increasing from 32% in 2013 to 79% in 2018. However, the treatment-to-control conversion remained low at 18%, indicating that 19% of the treated hypertensive population did not achieve control. Huge care gaps are shown in males vs females (Figure 1). Overall, more than 95% of the hypertensive population remains uncontrolled. Conclusion: The most significant drop in the hypertension care cascade occurs at the diagnostic phase, where over 70% of the hypertensive population remains undiagnosed. Despite improvements in treatment rates, the conversion from treatment to control remains low. Addressing the diagnostic gap is critical for enhancing hypertension control and reducing CVD risks in Indonesia.

Population dietary-metabolic characteristics and mortality from major cardiovascular disease subtypes: the Seven Contries Study 60-year follow-up

Background and aimDuring the last few years, the Seven Countries Study of Cardiovascular Diseases (SCS) produced some new analyses dealing with the relationships of a dietary score, the pool of dietary fatty acids and serum cholesterol with major types of cardiovascular disease (CVD) mortality in 10 cohorts of 6 countries made of middle-aged men followed-up for 60 years until extinction. This sparse evidence is condensed here to provide a coherent view. Methods and resultsThe Mediterranean Adequacy Index (MAI, a dietary score whose high levels depict the characteristics of the Mediterranean Diet), was highly and significantly associated in an inverse way, at country levels, with the Atherogenicity (ATI) and the Thrombogenicity (THI) indexes that included a series of dietary fatty acids. These indexes were highly and significantly associated in a direct way with country baseline serum cholesterol levels. Countries with high serum cholesterol had largely higher death rates from coronary heart disease (CHD) and lower rates from other heart diseases of uncertain etiology and stroke. The reverse was observed in countries with low serum cholesterol. ConclusionThe chain of diet, dietary fatty acids and serum cholesterol seems to be responsible in various ways for the different distribution of major CVD mortality subtypes in extincted cohorts.

Risk of Cardiovascular Events in Adults Aged 40 to 79 Years with Diagnosed Hypertension, High Cholesterol, and/or Diabetes but Not on Medications: Findings from Nationwide Cross-Sectional Studies.

Many people with diagnosed hypertension, high cholesterol, and/or diabetes are not receiving drug treatment, partly because they perceive their cardiovascular disease (CVD) risk as low. This study aimed to quantify the risk for future CVD events, either first or recurrent, in people with diagnosed hypertension, high cholesterol, and/or diabetes but not on medications for any of these conditions. Participants aged 40-79 years who had been diagnosed with hypertension, high cholesterol, and/or diabetes but were not on medications were identified from National Health and Nutrition Examination Surveys cycles 1999 to 2018. Among them, those with known CVD and those without known CVD but with complete data for estimating their 10-year CVD risk were included in this study. The participants were classified as (1) "high-risk" if they had known CVD or a 10-year predicted CVD risk ≥ 7.5% or (2) "low-risk" if they had a 10-year predicted CVD risk < 7.5%. Of the 5187 participants included, 2201 had known major CVD (n = 490, 9.45%) or a 10-year predicted CVD risk ≥ 7.5% (n = 1711, 32.99%), corresponding to a weighted proportion of 34.83% (95% CI: 33.15 to 36.51%) in the US general population. The proportions of high-risk participants were much higher in the elderly (65.50% for 60-69 years and 97.86% for 70-79 years), males (45.13%), and non-Hispanic Blacks (42.15%) than in others (all p < 0.001). These patterns were consistent across survey cycles during 1999-2018. Additional analyses that classified the participants into groups above or below the treatment threshold (rather than high- or low-risk groups) according to current guidelines yielded similar results. A comparison of the 2201 untreated high-risk participants with other participants who had been diagnosed with hypertension, high cholesterol, and/or diabetes and were on medications for these conditions showed that "lower BMI", "smaller waist circumference", and a "non-diabetic" status, among others, were associated with a higher likelihood of "not taking medications". In conclusion, approximately one-third of the US adults aged 40 to 79 years with diagnosed hypertension, high cholesterol, and/or diabetes but not on medications had known CVD or a 10-year predicted CVD risk ≥ 7.5%, and this proportion was little changed over the past two decades. Interventions targeted at the subgroups with particular characteristics identified in this study may help improve the management of CVD and its risk factors.

A new biomarker in the diagnosis and prognosis of pulmonary thromboembolism: Serum profilin-1

ObjectivePulmonary Thromboembolism (PTE) is one of the major cardiovascular diseases with high morbidity and mortality. Early diagnosis and accurate prognosis are essential in clinical management. This study aimed to investigate the efficacy of serum Profilin-1(PFN1) in diagnosing and prognosis PTE. Materials and methodsThis study was conducted on patients older than 18 diagnosed with PTE and healthy volunteers with similar sociodemographic characteristics who applied to the emergency department between March 2022 and March 2023. ResultsIn the study, 102 patients diagnosed with PTE were in the patient group, and 64 healthy volunteers were in the control group. The median PFN1 level of the patient group was 2878 (124–5001) pg/mL, while the median PFN1 level of the control group was 579 (125–5001) pg/mL. The PFN1 level of the patient group was significantly higher than the control group (p < 0.001). PFN1 levels of 984.46 pg/mL and above had 76.47 % sensitivity and 79.69 % specificity in diagnosing PTE (AUC: 0.817; CI: 0.750–0.873; p < 0.0001). The median PFN1 level of patients with mortality was 5001 (1793.3–5001) pg/mL, while the median PFN1 level of patients without mortality was 1858 (124–5001) pg/mL. PFN1 levels of patients who developed mortality were significantly higher than those who did not develop mortality (p < 0.001). PFN1 levels of 3292.1 pg/mL and above had 90.91 % sensitivity and 71.25 % specificity in PTE prognosis (AUC: 0.861; CI: 0.778–0.921; p < 0.0001). ConclusionSerum Profilin-1 levels are helpful as a diagnostic and prognostic indicator in PTE.

The Role of Alarmins in the Pathogenesis of Atherosclerosis and Myocardial Infarction.

Atherosclerosis is a condition that is associated with lipid accumulation in the arterial intima. Consequently, the enlarging lesion, which is also known as an atherosclerotic plaque, may close the blood vessel lumen, thus leading to organ ischaemia. Furthermore, the plaque may rupture and initiate the formation of a thrombus, which can cause acute ischaemia. Atherosclerosis is a background pathological condition that can eventually lead to major cardiovascular diseases such as acute coronary syndrome or ischaemic stroke. The disorder is associated with an altered profile of alarmins, stress response molecules that are secreted due to cell injury or death and that induce inflammatory responses. High-mobility group box 1 (HMGB1), S100 proteins, interleukin-33, and heat shock proteins (HSPs) also affect the behaviour of endothelial cells and vascular smooth muscle cells (VSMCs). Thus, alarmins control the inflammatory responses of endothelial cells and proliferation of VSMCs, two important processes implicated in the pathogenesis of atherosclerosis. In this review, we will discuss the role of alarmins in the pathophysiology of atherosclerosis and myocardial infarction.

Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease

ObjectiveType 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate...

Cardiovascular Risk Factors Predicting Cardiovascular and Cancer Deaths in a Middle-Aged Population Followed-Up for 61 Years until Extinction.

To study the relationships of cardiovascular risk factors with cancer and cardiovascular mortality in a cohort of middle-aged men followed-up for 61 years. A rural cohort of 1611 cancer- and cardiovascular disease-free men aged 40-59 years was examined in 1960 within the Italian Section of the Seven Countries Study, and 28 risk factors measured at baseline were used to predict cancer (n = 459) and cardiovascular deaths (n = 678) that occurred during 61 years of follow-up until the extinction of the cohort with Cox proportional hazard models. A model with 28 risk factors and cancer deaths as the end-point produced eight statistically significant coefficients for age, smoking habits, mother early death, corneal arcus, xanthelasma and diabetes directly related to events, and arm circumference and healthy diet inversely related. In the corresponding models for major cardiovascular diseases and their subgroups, only the coefficients of age and smoking habits were significant among those found for cancer deaths, to which healthy diet can be added if considering coronary heart disease alone. Following a competing risks analysis by the Fine-Gray method, risk factors significantly common to both conditions were only age, smoking, and xanthelasma. A sizeable number of traditional cardiovascular risk factors were not predictors of cancer death in a middle-aged male cohort followed-up until extinction.

Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study

Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. For the Spanish translation of the abstract see Supplementary Materials section.

Endothelium-mediated vasodilation: associations with cardiometabolic diseases and their risk factors in aging

Aim. To evaluate the association of flow-mediated vasodilation (FMD) with cardiometabolic diseases (CMDs) and their risk factors (RF) in old age.Material and methods. The study was conducted in the Russian population cohort of the HAPIEE project (Novosibirsk, 2015-2018). Endothelial function was assessed in a random subsample (788 men and women aged 55-84 years) using ultrasound measurements of the brachial artery FMD. Endothelial dysfunction (ED) was recorded with FMD &lt;10%. Cardiovascular diseases (CVD) and risk factors were assessed using standard epidemiological methods.Results. The incidence of hypertension (HTN) was 78,8% (the same in men and women), major CVDs — 21,7% and 17,1%, type 2 diabetes (T2D) — 18,7% and 19,1% in men and women, respectively. The mean FMD values were 2,7% (SD 7,32) and 3,2% (7,19), while the prevalence of ED was 88,2% and 85,8% in men and women, respectively, and did not differ significantly by sex. Men with ED had higher levels of blood triglycerides (125,1 (71,23) vs 102,7 (45,79) mg/dl; p=0,033), waist/hip circumference indices (0,94 (0,050) vs 0,92 (0,076); p=0,009) and body weight (27,7 (45,79) vs 26,5 (4,36) kg/m2; p=0,077). In women, a tendency towards an association of ED with smoking was revealed (p=0,067). There were no associations of ED with HTN, T2D and CVD in men and women.Conclusion. The PMD test demonstrated a high incidence of ED in a population sample of 55-84 years old. ED is associated with metabolic risk factors in men and smoking in women. No associations of PMD with CMDs were found, presumably due to the high incidence of ED and cumulative disease in the elderly. Modification of metabolic risk factors and smoking cessation are relevant at any age to prevent the progression of ED.

Sleep duration irregularity and risk for incident cardiovascular disease in the UK Biobank.

Emerging evidence supports a link between circadian disruption as measured by higher night-to-night variation in sleep duration and increased risk of cardiovascular disease (CVD). It remains unclear whether this association varies by CVD types or may be modified by average sleep duration and genetic risk for CVD. Our prospective analysis included 86,219 UK Biobank participants who were free from CVD when completing 7 days of accelerometer measurement in 2013-2016. Sleep irregularity was evaluated by the standard deviation (SD) of accelerometer-measured sleep duration over 7 days. Incident major CVD events, defined as fatal or nonfatal myocardial infarction (MI) and stroke, were identified through linkage to Hospital Episode Statistics data until May 31, 2022. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs for associations of sleep duration SD with risk for major CVD events overall and for MI and stroke separately. We documented 2,310 incident cases of major CVD events (MI: 1,183, stroke: 1,175) over 636,258 person-years of follow-up. After adjusting for sociodemographic factors and family history of CVD, the HR (95% CI) associated with a 1-hour increase in sleep duration SD was 1.19 (1.10, 1.27) for CVD (p-trend<0.0001), 1.23 (1.11, 1.35) for MI (p-trend<0.0001), and 1.17 (1.05, 1.29) for stroke (p-trend=0.003). Additional adjustment for lifestyle factors, co-morbidities and sleep-related factors modestly attenuated these associations. Higher sleep irregularity was associated with higher CVD risk irrespective of genetic risk (p-interaction=0.43), but this association was stronger among individuals with longer average sleep duration >8 hours (p-interaction=0.006). Higher night-to-night variation in accelerometer-measured sleep duration was associated with consistently higher risks for major CVD events. The association did not seem to be modified by genetic risk for CVD and was more pronounced in long sleepers.

Wine intake and 45-year mortality in middle-aged men with high alcohol consumption: The Italian rural areas of the Seven Countries Study

Research into the relationship between alcohol consumption and health has a long-standing history. Previous studies have revealed the beneficial effects of moderate alcohol consumption on cardiovascular disease (CVD) and all-cause mortality compared to abstainers and heavy drinkers. To study the long-term impact of wine intake on mortality, we conducted a study involving 1284 men aged 45 &amp;ndash; 64 years in 1965, followed over a period of 45 years. We analyzed their wine-drinking habits in relation to all-cause mortality and specific causes using the Cox model. In addition, we utilized a multiple regression model with age at death as the dependent variable adjusted for age, smoking habits, body mass index, physical activity, dietary score, and comorbidity index. At baseline, 97.7% of participants were drinkers, consuming alcohol at an average of 77.4 g/day (mostly from wine). After 45 years, 98.4% of men had passed away. Our findings revealed a J-shaped relationship between alcohol intake and mortality from major CVD and all causes, while the relationship was roughly linear for cancer and liver cirrhosis. The relationship with CVD and all-cause mortality remained J-shaped, even when abstainers were excluded from the analysis, indicating potential health benefits for those consuming an average of 52 g/day (range: 47 &amp;ndash; 70 g) and a 34% excess in mortality for those consuming an average of 176 g/day (range: 142 &amp;ndash; 570 g). The average age at death for the reference class was 3.5 years higher compared to abstainers and 3.8 years higher compared to the upper class (average: 176 g/day). Reducing alcohol intake during the first 20 years of follow-up was beneficial in terms of life expectancy. In a lifetime follow-up, the relationship between alcohol consumption and mortality formed a J-shaped curve for CVD and all-cause mortality, even when excluding abstainers. Thus, relatively high wine consumption is more beneficial than lower intakes, especially when associated with vigorous physical activity at work &amp;ndash; a common practice among rural men in the 1960s.

Inflammatory Alterations to Renal Lymphatic Endothelial Cell Gene Expression in Mouse Models of Hypertension.

Hypertension (HTN) is a major cardiovascular disease that can cause and be worsened by renal damage and inflammation. We previously reported that renal lymphatic endothelial cells (LECs) increase in response to HTN and that augmenting lymphangiogenesis in the kidneys reduces blood pressure and renal pro-inflammatory immune cells in mice with various forms of HTN. Our aim was to evaluate the specific changes that renal LECs undergo in HTN. We performed single-cell RNA sequencing. Using the angiotensin II-induced and salt-sensitive mouse models of HTN, we isolated renal CD31+ and podoplanin+ cells. Sequencing of these cells revealed three distinct cell types with unique expression profiles, including LECs. The number and transcriptional diversity of LECs increased in samples from mice with HTN, as demonstrated by 597 differentially expressed genes (p &lt; 0.01), 274 significantly enriched pathways (p &lt; 0.01), and 331 regulons with specific enrichment in HTN LECs. These changes demonstrate a profound inflammatory response in renal LECs in HTN, leading to an increase in genes and pathways associated with inflammation-driven growth and immune checkpoint activity in LECs. These results reinforce and help to further explain the benefits of renal LECs and lymphangiogenesis in HTN.