Incidence Of Cardiovascular Disease Research Articles

Incidence of cardiovascular diseases among breast cancer patients: a nationwide registry study 2013-2020

Abstract Background and aims There is evidence to suggest that breast cancer (BC) treatment is associated with an increased risk of developing cardiovascular disease (CVD). Several countries have introduced clinical measures to reduce the impact of breast cancer treatment on cardiovascular function including activated breathing control during radiotherapy, lower radiation doses, and maximum anthracycline doses. The overall aim of this study was therefore to investigate whether breast cancer patients still exhibit higher rates of cardiovascular disease than the general population. Methods We conducted a registry-based cohort study using linked data from four nationwide health registries. Out study population included all Norwegian patients diagnosed with BC between 2013-2020 and matched them by age to 10 controls without BC. Health outcomes were measured from 2008 to 2021. We estimated the cumulative incidence from index date, for ten selected CVDs. For BC patients, the index date was defined as date of BC diagnosis. For controls, the index date was defined as the date of BC diagnosis for the matched BC patient. A wash-out period of 5 years was applied to identify incident cases of CVD. Results The study population included 27,535 patients with BC and 269,9994 matched controls. Median age in both groups was 62 years (IQR: 20). Prior to index date, there were no significant differences in the prevalence of heart valve disease, chronic ischemic heart disease heart failure and peripheral vascular disease in BC patients compared to controls (p>0.05) (Table 1). Hypertensive heart disease, pulmonary embolism, atrial fibrillation, and other cardiac arrythmias were more prevalent in BC patients, while angina pectoris and acute myocardial infarction were more prevalent among controls. After the index date, the incidence proportion for heart valve disease, hypertensive heart disease, pulmonary embolism, atrial fibrillation, other cardiac arrythmias, and heart failure were higher in BC patients compared to controls (p<0.001) (Table 2). No significant differences were found for angina pectoris, acute myocardial infarction, chronic ischemic heart disease, and peripheral vascular disease. Conclusion Breast cancer is still associated with an increased risk of developing several CVDs in current clinical practice, compared to matched controls without breast cancer.Baseline characteristicsIncidence of CVD

Antibodies against phosphorylcholine in prediction of cardiovascular disease among women: a population-based prospective cohort study

Abstract Background and aims Antibodies against phosphorylcholine (anti-PC) have been reported as associated with protection against atherosclerosis, cardiovascular disease (CVD) and other chronic inflammatory diseases. Underlying potential mechanisms have been demonstrated and include anti-inflammatory, clearance of dead cells and inhibition of oxidized low-density lipoprotein-effects. The aim is to study the role of IgM anti-PC and incident CVD among women, where less is known than among men in the general population. Methods In a total of 932 women, 66 ± 6 years old at baseline, from the population-based Swedish Mammography Cohort IgM anti-PC levels of sera were measured using ELISA. Prospective associations with any first CVD, ischemic heart disease (IHD), myocardial infarction (MI) and ischemic stroke were assessed using Cox proportional hazard regression, generating hazard ratios (HR) and 95% confidence intervals (CI). The model was adjusted for potential confounding factors. Results Over the course of 16 years (14,900 person-years), we identified 113 cases of composite CVD, - 69 cases of ischemic heart disease (IHD), 44 cases of myocardial infarction (MI) and 50 cases of ischemic stroke. IgM antiPC was statistically significantly inversely associated with risk of CVD, IHD and MI, but not with ischemic stroke. Comparing the highest tertile with lowest, we observed multivariable-adjusted HR of 0.26 (95% CI: 0.10–0.66; p-trend <0.01) for MI. Conclusions IgM anti-PC may play an active role in inhibition of CVD development in women, especially MI. Elevating anti-PC concentration through immunization, may be a future development in CVD prevention.

Associations of omega-3 fatty acid subclasses with cardiovascular diseases in 500,000 individuals

Abstract Increased blood levels of omega-3 fatty acids have consistently been shown to be associated with reduced risk of cardiovascular diseases (CVD). However, large scale placebo-controlled trials of omega-3 supplementation have had discordant results: in 2018 REDUCE-IT reported a 25% risk reduction, whereas in 2020 STRENGTH reported no risk reduction. The two trials had both different placebos (mineral vs corn oil) and omega-3 formulations (EPA vs DHA+EPA). There is not yet a consensus on what explains these results. Here we describe the profiling of omega-3 fatty acid subclasses, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) with nuclear magnetic resonance (NMR), and test their associations with incident CVD in 500,000 individuals from UK Biobank. We utilized 500 MHz NMR spectrometers to analyze total omega-3 and its subclasses in EDTA plasma samples and employed biomarker-specific quantification algorithms to measure their absolute concentrations. In this study, we developed a novel algorithm to quantify EPA, complementing previously described algorithms for omega-3 and DHA. Correlation (r^2) of this novel NMR-based quantification and gas chromatography-based measurements was 0.77 for EPA. On average, DHA comprised 44.5% of the total omega-3 concentration, EPA accounted for 22.2%, and other subclasses constituted 34.3% in the cohort. We computed age and sex adjusted associations of omega-3, DHA, and EPA with 10-year risk of CVD among individuals who were not taking cholesterol lowering medication. We discovered protective associations: for DHA a hazard ratio of 0.85 (0.86-0.89, 95% confidence interval) per standard deviation versus 0.96 (0.95-0.98) for EPA, and 0.95 (0.93-0.97) for total omega-3 (Figure). Since DHA (used in the STRENGTH trial with a null result) has a significantly stronger epidemiological association than EPA, these results from a large-scale observational study do not support the hypothesis that the differential use of DHA and EPA in the REDUCE-IT and STRENGTH trials explains their divergent results.Figure

LE8 score in relation to cardiovascular disease and mortality in individuals with diabetes

Abstract Background Evidence regarding the potential health effects of Life’s Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited. Purpose We aimed to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality, among individuals with T2D. Methods We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range, 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, BMI, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations. Results During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted hazard ratios and 95%CIs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (0.53, 0.59) for CVD incidence, 0.57 (0.53, 0.62) for heart disease incidence, 0.53 (0.49, 0.57) for stroke incidence, and 0.73 (0.69, 0.78) for total mortality (all p trend<0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17%-42% lower risk of CVD incidence, heart disease incidence, stroke incidence, and total mortality. These associations persisted in subgroup analysis stratified by age, sex, BMI, smoking status, alcohol intake, family history of diabetes and CVD, and follow-up time. Conclusions Higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D. These findings further support the tremendous benefit of adhering to a high CVH, defined as the LE8 in reducing the subsequent burden of cardiovascular complications and improving overall health in individuals with T2D.Main TableMain Figure

External validation of the Systematic COronary Risk Evaluation 2 (SCORE2) model in cancer patients

Abstract Background Guidelines recommend cardiovascular disease (CVD) risk stratification before cancer treatment to better identify patients for intensified follow-up or cardioprotective treatment. Only a limited number of CVD risk stratification tools exists for cancer patients which at present is not widely used nor extensively validated. The ESC Guidelines on Cardio-oncology 2022 suggest using traditional CVD models like the SCORE2 (Systematic Coronary Risk Estimation 2). However, external validation in cancer populations is lacking. Purpose Our aim was to study the prevalence of CVD risk factors and incidence of cardiovascular events in a cancer cohort and externally validate the Systematic COronary Risk Evaluation 2 (SCORE2) model in this context. Methods We included 1058 patients from a large-scale populational study without diabetes or established CVD aged 40 to 69 years and diagnosed with cancer between 2006 and 2012. Participants were assessed for cardiovascular risk factors at baseline and followed until Sept 2023. The Norwegian Cancer Registry provided patient specific information about cancer characteristics and therapy. The primary outcome was the combination of myocardial infarction (MI), stroke or CVD mortality, which was retrieved from the local hospitals’ registries and the national causes of death registry. Performance was assessed using smooth calibration curves of predicted and observed risk and Harrel’s C-statistic for discrimination, both corrected for competing risks. SCORE2 was recalibrated by adapting the model with a single multiplicative constant based on the expected-to-observed ratio (E/O-ratio). Results The most common cancer types were gastrointestinal cancer (19%), male genital including prostate cancer (19%) and breast cancer (18%). Mean (SD) age was 58.6 (7.6) years, 54% were female. Prevalence of cardiovascular risk factors are shown in Table 1. In total, 121 (11%) individuals had a CVD event (MIs 53 (44%), strokes 46 (38%) and CVD deaths 22 (18%)) during a median (interquartile range) follow-up of 11.1 (3.4 to 13.1) years, and 360 (34%) died due to non-CVD causes. Calibration plots showed adequate agreement between estimated and observed 10-year prognosis after recalibration (C-statistics 0.685, 95% CI 0.643 to 0.728), Figure 1. E/O-ratio for men was 0.65 and for women 0.63, indicating underestimation of the observed CVD incidence. After recalibration, the median estimated 10-year risk was 8.1% (IQR 5 to 11), 36% had >10% 10-year risk and 9% had >15% 10-year risk. Conclusion SCORE2 underestimated CVD risk in a general cancer population but showed adequate agreement after recalibration and C-statistics aligned with the original external validation cohorts. SCORE2 is useful also in cardio-oncology setting (after recalibration) to identify individuals at higher risk of developing CVD.

Sleep characteristics in relation to cardiovascular disease incidence and mortality in individuals with diabetes

Abstract Background/Introduction Evidence regarding the potential health effects of sleep characteristics among individuals with type 2 diabetes (T2D) is limited. Purpose We aimed to examine sleep characteristics in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease (CHD), and stroke, and all-cause and cause-specific mortality among individuals with T2D. Methods We prospectively followed 21,902 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1986-2018, Health Professionals Follow-Up Study: 1986-2018). Sleep characteristics, including sleep duration, snoring, sleep apnea, and sleep quality, were repeatedly assessed using self-reported questionnaires at baseline and follow-up. Associations of sleep characteristics with CVD risk and mortality were assessed using Cox proportional hazards models with adjustments for demographic, dietary and lifestyle factors, and medical history. Results During 170,355 and 196,458 person-years of follow-up in participants with T2D, there were 2,486 incident CVD events and 3,922 deaths, respectively. Compared with sleeping for 7-8 h/day, the multivariable-adjusted hazard ratios (HRs) of sleeping for ≤5 h/day were 1.21 (1.02, 1.45) for CVD incidence, 1.24 (1.20, 1.51) for CHD incidence, 1.40 (1.24, 1.58) for total mortality, 1.52 (1.20, 1.92) for CVD mortality, and 1.27 (1.01, 1.61) for other non-CVD and non-cancer mortality, while the HRs of ≥10 h/day were 1.42 (1.21, 1.66) for total mortality, and 1.63 (1.20, 2.10) for other non-CVD and non-cancer mortality. Furthermore, compared with participants without habitual snoring, those with habitual snoring had a 21%, 24%, 18%, and 33% higher risk for CVD incidence, CHD incidence, CVD mortality, and total mortality, respectively. Compared with participants without diagnosed sleep apnea, those with sleep apnea had a 27%-58% higher risk for CVD incidence, CVD mortality, and total mortality. In addition, lower habitual sleep quality, including sleep difficulties and restless sleep, was associated with a substantially higher risk of CVD, CHD, or CVD mortality. No associations were observed between sleep characteristics with risk of stroke and cancer mortality in individuals with T2D. Conclusions Short and long sleep durations as well as habitual snoring, sleep apnea, and lower sleep quality were independently associated with higher risks of CVD incidence and mortality, particularly CVD mortality in individuals with T2D.

External validation of the HFA-ICOS risk stratification tool for prediction of cardiovascular complications after cancer treatment

Abstract Background The 2022 ESC Guidelines on Cardio-oncology recommends using the HFA-ICOS (Heart Failure Association and the International Cardio-Oncology Society) four-category risk stratification tool to predict risk of heart failure (HF) and other cardiovascular disease (CVD) complications during and after cancer therapy. However, the actual risk associated with assignment to these categories is unknown. Purpose We aimed to assess the prognostic performance the HFA-ICOS risk stratification tool in a large cancer subpopulation of a general health survey linked to Norwegian health registries. Methods Participants in a large-scale population study diagnosed with cancer between 2006 and 2012 were included (n=2290) and followed for CVD endpoints until Sept 2023. CVD risk factors were measured at baseline between 2006 and 2008. The Norwegian Cancer Registry provided detailed information about cancer characteristics and therapy. We retrieved CVD endpoints from the local hospitals’ registries and the national causes of death registry. Kaplan Meier survival curves were used to estimate the risk of the combined endpoint of HF hospitalization, myocardial infarction (MI), stroke and CVD death, as well as HF hospitalization alone and non-CVD death. Harrel’s C-statistic was used to validate the discriminative abilities. Results Mean (SD) age was 65.8 (12.4) years, 48% were female, cancer types and cardiovascular risk factors are shown in Table 1. During a median (interquartile range) follow-up of 6.9 (1.4 to 12.2) years, there were 460 first CVD events (HF hospitalizations 87 (19%), MIs 161 (35%), strokes 130 (28%), CVD deaths 82 (18%)) and 1003 (44%) non-CVD deaths. When applying the HFA-ICOS tool, 649 (28%) were assigned to the low-risk category, 912 (40%) to medium, 661 (29%) to high-risk and 68 (3%) to the very high-risk category. Between the HFA-ICOS risk categories, there were clear differences in the observed risk of CVD events, HF hospitalizations and non-CVD mortality (Figure 1). CVD incidence was highest in the highest HFA-ICOS risk categories (7% in the low risk group, 21% in the medium risk group, 31% in the high risk group and 37% in the very high-risk group (p-value <0.001)). C-statistics for predicting CVD events was 0.696 (95% CI, 0.674 to 0.718). When only assessing patients with HF hospitalizations as (first) outcome (n=116), the risk of HF was higher in the high and very high-risk groups (0% in the low risk group, 4% in the medium, 9% in high and 21% in the very high risk group (C-statistics 0.794 (95% CI, 0.762 to 0.827)). Conclusion The HFA-ICOS baseline risk assessment was useful to identify patients at risk of both clinical overt heart failure and other major CV complications and non-CV death in a population with a variety of cancers. These results can help communicate absolute risks to cancer patients, which may be helpful in the shared decision-making for cardioprotective treatment and intensified follow-up.

Mean body mass index during 20 years of follow-up and cardiovascular disease incidence: results from the ATTICA cohort study (2002-2022)

Abstract Background/Introduction The Global Burden of Disease study has estimated that the burden of increased body mass index (BMI) (i.e., approximately >2.000.000 deaths and >70.000.000 disability-adjusted life years) was predominantly dominated by cardiovascular disease (CVD) during 1990–2017. However, the lifelong body weight (BW) status and its relation to CVD risk remains poorly elucidated. Purpose The purpose of this study was to evaluate the relationship between mean BMI during a 20-year period and CVD incidence. Methods Participants initially free-of-CVD from the ATTICA cohort study were used (n=1,348). At baseline and the 10- and 20-year follow-up, CVD events were assessed, according to WHO-ICD-10. Based on three measurements of weight and height, BMI for each measurement was calculated, and, afterwards, the mean BMI during the whole 20-year period was computed. Results During the whole 20-year period, 41% (n=552) of participants consistently had a normal BW, 48% (n=651) had overweight and 11% (n=145) had obesity. The 20-year CVD incidence was: 8.0% (n=44), 14.9% (n=97) and 19.3% (n=28) in those who consistently had a normal BW, overweight and obesity, respectively (p-value<0.001). In multi-adjusted Cox proportional hazards models, adjusted for age, sex, clinical and lifestyle characteristics, compared to participants who consistently had a normal BW, those who had overweight as well as those who had obesity had almost 2 times higher risk to develop CVD during the 20-year period [Hazard Ratio-HR: 1.73, 95%Confidence Interval-CI: 1.13-2.66 and HR: 2.04, 95%CI: 1.11-3.76, for participants with overweight and obesity, respectively]. Conclusion The study findings highlight that, despite the observations of the J-shaped relationship between BMI and all-cause mortality observed in some studies, both overweight and obesity can be significant risk factors for CVD, when lifelong BW status is assessed. Therefore, currently, new lifelong measures are needed to prevent and manage the pervasive overweight and obesity.

Adherence to a sustainable diet, measured via the EAT-Lancet Index, predicts incident short-term and long-term cardiovascular disease incidence: the ATTICA study (2002-2022)

Abstract Background/Introduction The World Heart Federation has estimated that air pollution was the second most fatal modifiable risk factor for cardiovascular disease (CVD), causing approximately 5 million CVD deaths in 2021. Diets and food systems can affect the environment; however, research scarcely focuses on the association between planet-healthy dietary habits and CVD risk. Purpose The purpose of this study was to evaluate the adherence to a sustainable diet and CVD incidence during 20 years of follow-up. Methods Participants initially free-of-CVD from the ATTICA study were used (n=1,958). CVD events were assessed at baseline and at all follow-ups (i.e., 2002, 2012, 2022) according to WHO-ICD-10. Adherence to a sustainable diet was assessed via the EAT-Lancet Index (EAT-LI) (Education and Agriculture Together-EAT) (range: 0-42) based on the published algorithm. Results CVD incidence was 16.2% (n=317 incident cases) at 10-years and 35.3% (n=691 incident cases) at 20-years. Mean EAT-LI was: 17.3 (6.7) for the total sample. EAT-LI was lower in those that had a CVD event during the follow-up, i.e., EAT-LI: 10.5 (6.3) vs 18.5 (5.9) at 10-years (p<0.001) and 10.9 (6.4) vs 20.8 (3.8) at 20-years (p<0.001), in participants with and without a CVD event, respectively. In multi-adjusted analyses, adjusted for age, sex, body mass index trajectories, lifestyle trajectories, and clinical factors (diabetes, hypercholesterolemia, hypertension), higher adherence to a sustainable diet was inversely associated with CVD risk at a short-term and a long-term period (i.e., at 10 and 20 years). Specifically, per 1/42 increase in the EAT-Lancet index, CVD risk was reduced by 11% [Hazard ratio-HR: 0.89, 95%Confidence Interval: 0.86-0.93] and by 16% [HR: 0.84, 95%CI: 0.80-0.89] at 10 and 20 years, respectively. Conclusion Future guidelines for CVD prevention should take into account the sustainable nature of dietary habits, to efficiently nourish the growing world population, and concomitantly protect heart and planet health.

Trends in cardiovascular disease incidence among 22 million people in the UK over 20 years: population based study.

Trends in cardiovascular disease incidence among 22 million people in the UK over 20 years: population based study.

The associations of triglyceride glucose and its derived indexes with 10-year cardiovascular disease risk in a Chinese community-based population

Abstract Background The triglyceride-glucose (TyG) index has been regarded as a reliable surrogate marker of insulin resistance and an independent predictor of cardiovascular outcomes. However, the associations of the derived TyG indexes with incident CVD risk are controversial, and that the relevant data are sparse for the Chinese population studies. Objectives We aimed to investigate the association of TyG index and its derived indexes with incident CVD risk and to compare their predictive capacity in the Chinese community-based population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who were free of prevalent stroke or myocardial infarction at baseline. The primary endpoint was a new-onset major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, first non-fatal stroke, and first non-fatal acute myocardial infarction. Cox proportional-hazards regression analyses and time-dependent receiver operator characteristic curve analyses were performed. Results A total of 8,806 participants were included. The mean age was 56.51 ± 8.93 years, and 5,679 (64.5%) were female. The median value of TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were 8.71 (8.34-9.12), 226.37 (201.02-252.87), 720.80 (653.52-791.03), and 4.47 (4.07-4.90), respectively. During a mean 9.7-year follow-up, a total of 877 (10%) cases of MACE were recorded. The Kaplan–Meier curves showed significant differences in cumulative hazards of new-onset MACE among tertiles of abovementioned indexes (Log rank P < 0.0001) (Figure 1). Multivariable Cox regression analyses revealed that TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were positively associated with the hazards of MACE. Compared with tertile 1, the multivariable adjusted HRs (95% CIs) of incident CVD for tertile 3 were 1.26 (1.01-1.56), 1.57 (1.15-2.14), 1.54 (1.19-2.00), and 1.81 (1.40-2.33) for TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively (Figure 2). There are no significant differences in the Harrell's C indexes among the various indexes compared to the TyG index (TyG index: 0.758 [0.743-0.774], TyG-BMI: 0.758 [0.743-0.773], TyG-WC: 0.758 [0.743-0.774], and TyG-WHtR: 0.760 [0.745-0.775]). Conclusions Higher TyG and its derived indexes are significantly associated with an increased risk of 10-year MACE. Our results suggest that TyG and its derived indexes may serve as a useful marker for stratifying CVD risk in the general population.

Cardiovascular disease history as a predictor for adverse outcomes in frail older adults admitted to acute geriatric settings: 12-month outcomes from an Australian frailty registry

Abstract Introduction Frailty is common in older adults with cardiovascular disease (CVD), with prevalence between 25-62% (1). The incidence of CVD increases with age, yet the outcomes of frail older adults with a history of CVD who present to acute geriatric settings, is not well understood. Purpose To report the association of CVD and rehospitalisation and/or mortality at 12 months in a cohort of frail older adults enrolled in an Australian frailty registry. Methods A convenience sample of participants enrolled in the frailty registry, with 12-month follow-up completed. The frailty registry is a prospective cohort study of adults admitted to the rehabilitation and aged care departments at two Australian hospitals. Frailty was assessed using the Clinical Frailty Scale (CFS), a score of 1-4 is ‘non-frail’, 5-6 is ‘mild-moderately frail’ and 7-9 is ‘severely frail’ (2). For this study, ‘CVD’ was defined as having a history of either heart failure, stroke, or atrial fibrillation. The cumulative incidence of first rehospitalisation and/or death during the first 12 months post discharge was estimated using one minus the Kaplan-Meier estimate of the survival function. Association between CVD (history of CVD, and type of CVD condition) and the composite endpoint were analysed. Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox models incorporating variables of interest and potential confounders. Results A total of 592 participants were included, median age was 82 years, 59% (n= 349) were female. The majority were frail with 50% (n= 295) classified as mild-moderately frail and 21% (n= 123) classified as severely frail. Almost half (45%, n= 265) had a history of CVD. The incidence of frailty (CFS score ≥5, mild-severely frail) was higher in those with CVD compared to those without CVD (76% vs 66%). A history of CVD was significantly associated with higher rate of first readmission or death within 12 months, compared to no history of CVD (p=0.017) (Figure 1). Of the three CVD conditions, heart failure was the only independent predictor of the composite endpoint (HR 1.60 [CI 1.14 -2.24], p=0.007). A CFS score of mild-moderately frail (HR 1.51 [CI 1.18 - 1.93, p=0.001) and severely frail were also independent predictors of the composite endpoint (HR 1.83 [CI 1.35- 2.48], p=<0.001) (Table 1). Conclusions A history of CVD has a significant impact on adverse outcomes in frail older adults admitted to acute geriatric settings. Frailty according to the CFS was independently predictive of rehospitalisation and mortality in this cohort. Heart failure was the only independent predictor of the composite endpoint. These findings underscore the importance of identifying and addressing CVD and in the context of frailty, emphasising the need for targeted interventions to improve outcomes in this vulnerable population.Figure 1.Table 1.

Prevecardio: a single-visit population screening model for detection and prevention of 10-year cardiovascular risk

Abstract Introduction Cardiovascular diseases (CVDs) are a major contributor to global mortality. The early detection of cardiovascular risk factors, coupled with timely intervention strategies, is essential for CVD prevention. PreveCardio was developed as an innovative, single-visit population screening model designed to facilitate the early identification and management of cardiovascular risk factors within a population of 1 million in a European capital city region totaling 6 million inhabitants. Purpose This study aimed to ascertain the prevalence of cardiovascular risk factors within the general population and to evaluate the effectiveness of the PreveCardio model in estimating 10-year cardiovascular risks and promoting preventive interventions. Methods In this cross-sectional prevalence study, individuals aged 50 to 75 from a health network were randomly selected and invited to participate in a comprehensive health check. The 30-minute screening consisted of lifestyle evaluations, anthropometric measurements, and blood tests for lipid profiles and glycated haemoglobin. The methodology was designed to provide participants with immediate feedback on their results, cardiovascular health and practical guidance for risk management. Results From the 8,492 individuals solicited, 3,546 took part in the screening: 56,83% were female, mean age 61,17 ± 7,33 y.o. Picture 1 shows the population's percentages with various modifiable cardiovascular risk factors, including 20% with active smoking, 30% with sedentarism, 16% with risky alcohol consumption, 49% with non-adherence to the Mediterranean diet, 40% with overweight, and 30% with obesity. The screening revealed new diagnoses of LDL-hypercholesterolemia in 47% participants, high levels of blood pressure in hypertension range in 49%, prediabetes in 30% and diabetes in 2% (Picture 2). After use SCORE2 and SCORE-OP risk prediction algorithms, PreveCardio is estimated to potentially prevent between 39 to 202 fatal and non-fatal cardiovascular events over 10 years. Predictive modelling based on PreveCardio data projected that expanding the screening across the capital region could prevent at least 26,260 cardiovascular events over 10 years. Conclusion(s) PreveCardio has established itself as a viable and effective model for the early detection of cardiovascular risk factors in a general population. It holds significant promise for public health impact by potentially reducing the incidence of CVD through comprehensive screening and proactive intervention.

Effects of SGLT2 inhibitors on the cardiovascular outcomes in patients with cancer: a systematic review and meta-analysis

Abstract Introduction The incidence of cardiovascular diseases in cancer survivors has gradually increased due to well-documented drug-associated cardiotoxicity and the expanding population resulting from advances in cancer treatment. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) have demonstrated efficacy in reducing cardiovascular risk in patients with type 2 diabetes mellitus, independent of glycemic control. Previous bench and animal research, along with several cohort studies, suggest potential benefits of SGLT2 inhibitors on cardiovascular outcomes in patients with cancer, with or without anthracycline therapy. This systematic review and meta-analysis aim to explore the potential of SGLT2 inhibitors as a therapeutic intervention to reduce cardiovascular risks in cancer patients, especially those undergoing chemotherapy. Methods We systematically searched Cochrane, PubMed, and Embase from inception until February 29, 2024, without language restrictions. Observational cohort studies with a follow-up period of at least 1 year were included to analyze the effects of SGLT2 inhibitors on cardiovascular outcomes in type 2 diabetes patients with cancer. Inclusion and exclusion criteria were predefined. Using random-effects models, we calculated odds ratios (OR) and 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the impact of SGLT2 inhibitors on mitigating cardiotoxicity. Primary outcomes of interest were mortality, heart failure hospitalization, sepsis, and diabetic ketoacidosis. Results Six studies involving 2959 patients in the SGLT2i group and 29169 patients in the non-SGLT2i group were included. Type 2 diabetes patients receiving SGLT2i exhibited significantly lower odds of mortality than those without SGLT2i (OR=0.34, 95% CI=[0.26-0.46], I²=77%). Subgroup analysis revealed a similar reduction in mortality among patients on SGLT2i treated with anthracyclines (OR=0.44, 95% CI=[0.23-0.82], I²=69%). Odds ratios for heart failure hospitalization and sepsis were also significantly lower in the SGLT2i group than the non-SGLT2i group (OR=0.46, 95% CI=[0.35-0.60], I²=0%, and OR=0.28, 95% CI=[0.20-0.40], I²=0%, respectively). The risk for diabetic ketoacidosis was not increased in the SGLT2i group (OR=0.66, 95% CI=[0.20-2.17], I²=0%). Conclusion SGLT2 inhibitors demonstrate a reduction in mortality, heart failure hospitalization, and sepsis in type 2 diabetes cancer patients treated with or without anthracyclines in cohort studies. Our findings support the need for further investigation through randomized controlled trials.Forest plots of mortality with subgroupForest plots of other primary outcomes

Using deep learning to detect atherosclerotic plaques on carotid ultrasound images in the UK Biobank

Abstract Background Atherosclerosis is the main underlying cause of cardiovascular disease (CVD). Existing CVD risk assessment tools do not consider the burden of subclinical atherosclerosis. The presence of carotid plaques on carotid ultrasound is a well-known marker of subclinical atherosclerosis. The accumulation of population-scale data on the presence of atherosclerotic plaques, along with deep phenotyping, can allow not only to address the effectiveness of carotid ultrasound in routine clinical practice, but to shed light on the biology of atherosclerosis development. Purpose To develop an effective deep learning model for plaque detection in carotid ultrasound images in the UK Biobank. Methods We used 680 carotid ultrasound images with manually annotated plaques to train a deep learning model employing the YOLOv8 architecture. Different augmentation techniques were used to increase the generalizability of the model. The developed model was applied to automatically detect plaques in raw ultrasound images from 19,507 UK Biobank participants. Logistic and Cox regression were used to explore the associations of plaque presence and number as predicted by the model with conventional CVD risk factors and the risk of future CVD events over follow-up. To explore the genetic architecture of subclinical atherosclerosis, we conducted a genome-wide association study (GWAS) on plaque presence, followed by meta-analysis with data from the CHARGE Consortium. Results Our plaque detection model achieved high classification metrics of accuracy, sensitivity, and specificity (89.3%, 89.5%, and 89.2%, respectively) and detected atherosclerotic plaques in 44% of UK Biobank participants. As expected, plaques were more common among men than women and their prevalence increased linearly with age. Both plaque presence and number of plaques were correlated with conventional CVD risk factors including diabetes, hypertension, and hyperlipidemia, and showed strong associations with future risk of incident CVD events (Hazard Ratio for plaque presence: 1.48 [95%CI: 1.21-1.82], for 2 plaques or more: 1.65, [95% CI: 1.28-2.13]). Incorporating plaque-derived phenotypes minimally altered the C-index of the time-to-event model. GWAS meta-analysis of carotid plaque presence revealed 5 previously known loci, as well as a significant locus including the LPA gene that had not previously been associated with carotid plaque. Conclusion We have developed and implemented an efficient plaque detection model to data from the UK Biobank, which holds significant promise for studying atherosclerosis at a population-wide scale through integration with multiomics data and electronic health records.

Cardiovascular risk prediction using metabolomic biomarkers and polygenic risk scores: a cohort study and modelling analyses

Abstract Background/Introduction Metabolomic biomarker scores and polygenic risk scores (PRS) have shown promise for improving cardiovascular disease (CVD) prediction, but have not yet been evaluated in the context of current prediction models (SCORE2) and ESC recommendations for 10-year prediction of fatal and non-fatal CVD. Purpose To assess whether metabolomics biomarkers and PRSs can improve 10-year CVD risk prediction when added to SCORE2, and whether improvements are meaningful at ESC 2021 recommended risk thresholds for treatment consideration. Methods Metabolomics biomarker scores were constructed and compared to PRS and SCORE2 in 170,000 UK Biobank participants (5,096 incident CVD cases) aged 40–69 without previous CVD, diabetes, or lipid-lowering treatment. Improvement in risk discrimination when added to SCORE2 was assessed using Harrel’s C-index. Improvement in risk stratification following ESC guideline risk thresholds was assessed using categorical net reclassification. Population modelling was subsequently applied to estimate the impact on CVD prevention if applied at scale. Results Risk discrimination provided by SCORE2 (C-index: 0.718) was similarly improved by addition of metabolomic biomarker scores (ΔC-index: 0.011 [0.009–0.014]) and PRSs (ΔC-index 0.009; [0.007–0.012]). Addition of both metabolomic biomarker scores and PRSs to SCORE2 yielded the largest improvement risk discrimination, with ΔC-index 0.019 (0.016–0.022). Concomitant improvements in risk stratification were observed in categorical net reclassification index, with net case reclassification of 13.04% (11.67–14.41%). Modelling metabolic biomarker scores and PRSs for targeted risk-reclassification increased the number of CVD events prevented per 100,000 screened from 201 to 370 (ΔCVDprevented: 170 [158–182]) while essentially maintaining the number of statins prescribed per CVD event prevented. Conclusions Combining metabolomic biomarker scores and PRSs with SCORE2 moderately enhances prediction of first-onset CVD, and could have substantial population health benefit if applied at scale.

The relationship between retinal vascular parameters measured by artificial intelligence and the risk of new-onset cardiovascular disease in a Chinese community-based population

Abstract Background Studies on the association between retinal vascular diameter and tortuosity and the risk of new-onset cardiovascular disease (CVD) are controversial. The predictive value of retinal vascular parameters, measured through artificial intelligence (AI), for incident CVD risk in the community population, remains to be explored. Objectives Our study aims to investigate the association between retinal vascular parameters (diameter and tortuosity) measured through AI, and the risk of new-onset CVD in the Chinese community-based population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who were free of prevalent stroke or myocardial infarction and underwent retinal photography at baseline. By deep-learning algorithm, quantitative retinal vascular parameters were measured 0.5 to 1 disc diameter from the optic disc margin, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), curvature tortuosity arteriole (cTORTa), and curvature tortuosity venule (cTORTv). The primary endpoint was a new-onset major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, first non-fatal stroke, and first non-fatal acute myocardial infarction (AMI). The secondary endpoints included cardiovascular death, first stroke, and first AMI. Cox proportional-hazards regression analyses were performed. Results A total of 3,585 participants were included. The mean age was 56.49 ± 8.94 years, and 2,335 (65.1%) were female. Prevalence of prior hypertension and diabetes was 1594 (44.5%) and 676 (18.9%), respectively. During the follow-up (median, 7.53 years), there were 293 cases of new-onset MACE (8.2%), 44 cardiovascular deaths (1.2%), 226 strokes (6.3%), and 57 AMIs (1.6%). The Kaplan–Meier curves showed significant differences in cumulative hazards of new-onset MACE among tertiles of CRAE, CRVE, AVR, and cTORTa, but not for cTORTv (Figure 1). In Cox proportional-hazards models (Figure 2) adjusting for covariates, CRAE was negatively associated with the risk of new-onset MACE (per 10 μm increase, hazard ratio [HR]=0.95, 95% confidence interval [CI]: 0.92-0.99, P=0.009) and the risk of new-onset stroke (per 10 μm increase, HR=0.96, 95%CI: 0.92-1.00, P=0.04). Similarly, AVR was negatively associated with new-onset MACE risk (per 0.1 increase, HR=0.82, 95%CI: 0.72-0.94, P<0.001) and new-onset stroke risk (per 0.1 increase, HR=0.84, 95%CI: 0.73-0.98, P=0.022). No significant associations were observed between CAVE, cTORTa, and cTORTv with any of the primary or secondary endpoints. Conclusions CRAE and AVR, measured through AI, are associated with the risk of new-onset MACE in the Chinese population. These findings suggest the potential for AI-measured parameters in retinal vasculature to aid in stratifying CVD risk in the general population.

Association of insulin resistance with cardiovascular disease and all-cause mortality in type 1 diabetes mellitus: systematic review and meta-analysis

Abstract Background Insulin resistance (IR) is a key factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and is associated with a higher risk of cardiovascular disease (CVD) and mortality. However, the association between IR and these outcomes in type 1 diabetes mellitus (T1DM) is less clear. This systematic review and meta-analysis aimed to investigate the associations between CVD outcomes and IR in T1DM. Methods PubMed, EMBASE, and the Cochrane Library databases were searched from inception to 15 March 2023 and updated on 31 October 2023. Observational studies (cohort studies or post hoc analysis of clinical trials) reporting the associations between IR measured by estimated glucose disposal rate (eGDR) level and the risk of CVD and all-cause mortality in individuals with T1DM were eligible. Data, pooled by random effects models, were presented as hazard ratios (95% confidence intervals, CI). The primary outcomes were the composite CVD outcome and all-cause mortality. Results Eight studies involving 21,930 individuals were included, of which five studies involving 19,960 T1DM individuals reported the risk of CVD. During a median follow-up of 10 years, there were 2,149 cases of incident CVD. The pooled hazard ratio for composite CVD outcome per 1-unit increase in the eGDR index was 0.83 (95% CI 0.78–0.90, I2 = 58.9%). Five studies involving 19,403 T1DM individuals reported the risk of all-cause mortality. During a median follow-up of 10 years, a total of 1,279 deaths were observed. The pooled hazard ratio for all-cause mortality per 1-unit increase in the eGDR index was 0.84 (95% CI 0.81–0.87, I2 = 0%). Conclusions IR as measured by eGDR may be an additional risk factor for cardiovascular disease and all-cause mortality in individuals with T1DM. Modification of IR by lifestyle interventions or pharmacological treatments could be a viable therapeutic target to lower the risk of CVD in T1DM.Figure 1 Literature flowchartFigure2 Forest plot

Cardiovascular events risk in office-masked nocturnal hypertension defined by home blood pressure monitoring: the J-HOP nocturnal blood pressure study

Abstract Background Elevated nocturnal home blood pressure (BP) has been reported to be associated with increased risk for cardiovascular disease (CVD). Masked hypertension defined by home BP monitoring is also a strong risk factor for adverse CVD outcomes. However, no study has investigated the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk. Purpose This study aimed to examine the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk in a clinical practice-based population. Methods This was a prospective observational study including Japanese participants with CVD or high risk of CVD. Three office BPs were taken on two different occasions. Nocturnal home BP was measured three times per night for two weeks. The association between office-masked nocturnal hypertension and incident total CVD events (including fatal and non-fatal stroke and coronary heart disease) was examined using Cox regression. Results 2,545 participants were followed for the mean of 7.1 years (18,116 person-years), during which 152 (6.0%) CVD events occurred. Mean age (standard deviation) was 63.3 (10.3) years; 49.0% were male; 82.6% took antihypertensive medications. The proportions of participants with normotension (office BP <140/90 mmHg and nocturnal home BP <120/70 mmHg), white-coat hypertension (office BP ≥140/90 mmHg and nocturnal home BP <120/70 mmHg), office-masked nocturnal hypertension (office BP <140/90 mmHg and nocturnal home BP ≥120/70 mmHg), and sustained hypertension (office BP ≥140/90 mmHg and nocturnal home BP ≥120/70 mmHg) were 25.3%, 14.4%, 23.2%, and 37.1%, respectively. The office-masked nocturnal hypertensive group and sustained hypertensive group had higher incidence rates of total CVD events compared with the normotensive group. Relative to normotension, those with both office-masked nocturnal hypertension (adjusted hazard ratio [aHR] 1.72, 95% confidence interval [CI] 1.01–2.92) and sustained hypertension (aHR 1.75, 95%CI 1.03–2.96) had similarly increased CVD risk, even after adjustment for daytime home BP values. Conclusions Screening for office-masked nocturnal hypertension with home BP monitoring identifies a potentially important group of patients with increased risk for incident CVD events for whom additional preventative measures may be appropriate.

The prognostic value of metabolic dysfunction associated steatotic liver disease in acute myocardial infarction

Abstract Background Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. Methods This study compared the characteristics, and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. Results In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 24 years. The MASLD group had higher rates of obesity, diabetes, and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs 3.6%, p<0.001) at 30 days, with unfavorable mortality rates sustained in the long-term (18.3% vs 14.5%, p=0.001) compared to those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (HR 1.338, 95% CI 1.115-1.604). Conclusion MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.Kaplan Meier curve of long-term all-caus