OBJECTIVE: We aimed to investigate the interplay between low-density lipoprotein-cholesterol (LDL-C) and coronary plaque in asymptomatic cohorts undergoing coronary tomography angiography (CCTA) assessment in the United States.
METHODS: A cross-sectional analysis of baseline data from 1808 statin-naïve participants in the Miami Heart Study was conducted. We assessed CCTA-detected atherosclerosis (any plaque, noncalcified plaque, maximal stenosis ≥50%, high-risk plaque) across LDL-C levels, coronary artery calcium (CAC) scores (0, 1-99, ≥100), and 10-year cardiovascular risk categories.
RESULTS: Atherosclerosis presence varied across LDL-C levels: 40% of those with LDL-C ≥190 mg/dL had no coronary plaque, while 33% with LDL-C <70 mg/dL had plaque (22.4% with noncalcified plaque). Among those with CAC 0, plaque prevalence ranged from 13.2% (LDL-C <70 mg/dL) to 28.2% (LDL-C ≥190 mg/dL), noncalcified plaque from 13.2% to 25.6%, stenosis ≥50% from 0 to 2.6%, and high-risk plaque from 0 to 5.1%. Conversely, with CAC ≥100, all had coronary plaque, with noncalcified plaque prevalence ranging from 25.0% (LDL-C <70 mg/dL) to 83.3% (LDL-C ≥190 mg/dL), stenosis ≥50% from 25.0% to 50.0%, and high-risk plaque from 0 to 66.7%. Among low-risk participants, 76.7% had CAC 0, yet 31.5% had any plaque and 18.3% had noncalcified plaque. Positive trends between LDL-C and any plaque (17.9%-45.2%) or noncalcified plaque (12.8%-23.8%) were observed in the low-risk group, but no clear trends were seen in higher-risk groups.
CONCLUSIONS: Heterogeneity exists in subclinical atherosclerosis across LDL-C, CAC, and estimated cardiovascular risk levels. The value of CCTA in risk-stratifying asymptomatic adults should be further explored.

BACKGROUND: Globally, women 15-24 years are at heightened risk of sexual violence victimization, a risk factor for adverse mental, physical, and behavioral health outcomes. Sexual violence is common at universities and most often perpetrated by men, yet few evidence-based prevention strategies targeting men have been tested in low- and middle-income countries. GlobalConsent is a six-module, web-based educational program adapted from an efficacious U.S.-based program. Nine months post-treatment in a randomized trial in Vietnam, GlobalConsent reduced men\'s sexually violent behavior (odds ratio [OR] = 0.71, 95%CI 0.50-1.00) and increased prosocial intervening behavior (OR = 1.51, 1.00-2.28) relative to an attention-control. Evidence regarding optimal implementation strategies for scale up is needed.
METHODS: We will randomize six medical universities in North, Central, and South Vietnam to deliver GlobalConsent using two different packages of implementation strategies that vary in intensity. Higher-intensity strategies will include greater (1) pre- and post-implementation engagement with university leaders and faculty and (2) greater pre-implementation outreach, follow-up, and incentives for students to promote engagement and completion of GlobalConsent. Higher intensity universities will receive additional training and support for their added activities. We will compare implementation drivers and outcomes, intervention effectiveness, and cost-effectiveness across the two implementation bundles. Our mixed-methods comparative interrupted time series design includes (1) qualitative interviews and quantitative surveys with university leaders and implementation teams to assess implementation barriers and facilitators; (2) repeated surveys with leaders and faculty, implementation teams, and male students to assess multilevel implementation drivers and outcomes; (3) repeated surveys with male students to assess behavioral outcomes (sexual violence and intervening behavior) and mediating variables (knowledge, attitudes, affect, and capacities); and (4) time diaries and cost tracking to assess cost-effectiveness of the two implementation-strategies bundles.
CONCLUSIONS: This project is the first to assess packages of implementation strategies to deliver an efficacious web-based sexual violence prevention program for undergraduate men across all regions of Vietnam and synergizes with a violence-prevention training initiative (D43TW012188). This approach will produce rigorous evidence about how to disseminate GlobalConsent nationally, which holds promise to reduce gender-based health inequities linked to sexual violence as GlobalConsent is brought to scale.
BACKGROUND: NCT06443541. Retrospectively registered with ClinicalTrials.gov. Registered on June 05, 2024.

OBJECTIVE: Efficient primary prevention of diabetic kidney disease (DKD) is currently lacking. The identification of people at high DKD risk and timely intervention are key to preventing DKD. Therefore, a model to classify people according to their risk for developing DKD was developed previously and used in the current analysis to assess the effect of semaglutide versus placebo on primary DKD prevention.
METHODS: Participants with type 2 diabetes from the randomized, double-blind, placebo-controlled SUSTAIN 6 trial without DKD at baseline who received 0.5/1.0 mg semaglutide or placebo were grouped by baseline DKD risk, calculated using a validated model. The main post hoc outcome was the effect of semaglutide versus placebo on the proportion of participants who developed DKD [urinary albumin/creatinine ratio (UACR) ≥30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m2]. Additional post hoc outcomes included changes in DKD risk score, UACR and estimated glomerular filtration rate over time.
RESULTS: Of the total 1139 participants included in the analysis, 28.7% developed DKD; more participants with a high DKD risk (952/1139) developed DKD. Semaglutide significantly reduced the risk of developing DKD in both the total [odds ratio 0.56 (95% confidence interval: 0.42; 0.74; p < 0.0001)], and high DKD risk population [odds ratio 0.51 (95% confidence interval: 0.38; 0.69; p < 0.0001)] and significantly delayed DKD development versus placebo. The beneficial effects of semaglutide were largely driven by UACR changes. The number needed to treat for semaglutide in the high DKD risk population was 7.
CONCLUSIONS: This post hoc study indicates that semaglutide may have beneficial effects on primary DKD prevention in people with T2D.

BACKGROUND: Electrical storms (E-storms), defined as multiple fatal ventricular arrhythmias over a short period, negatively affect the prognosis of patients receiving an implantable cardioverter defibrillator or cardiac resynchronization therapy with a defibrillator (ICD/CRT-D). However, the prognostic impact of recurrent E-storms has not been well elucidated.
RESULTS: We analyzed the association between E-storm recurrences and mortality using data from 1,274 participants in the Nippon Storm Study, a prospective observational study conducted at 48 ICD/CRT-D centers in Japan. Differences in E-storm recurrences by patient characteristics were evaluated using the mean cumulative function (MCF), which is the cumulative number of E-storm episodes per patient as a function of time. Patients with multiple E-storms had a 3.39-fold higher mortality risk than those without E-storms (95% confidence interval 1.82-6.28; P<0.01). However, there was no significant difference in mortality risk between patients with a single E-storm and those without E-storms. The MCF curve exhibited a slower ascent in patients who received primary prevention ICD/CRT-D than in those who received secondary prevention ICD/CRT-D. However, when analyzing only patients with E-storms, the MCF curves demonstrated comparable trajectories in both groups.
CONCLUSIONS: E-storm recurrences may have a negative impact on prognosis. Once patients with primary prevention experience an E-storm episode, they face a similar risk of subsequent recurrent E-storms as patients with secondary prevention.

Populations undergoing extensive and rapid socio-economic transitions including historically disadvantaged communities face an increased risk of type-2 diabetes (T2D). In recent years, sedentary behavior and physical inactivity have been considered modifiable determinants when developing primary prevention programs to reduce T2D incidence. Reunion Island is a French overseas department with an increasing T2D population and a high level of socio-economic inequality. The objectives of our study were to identify the individual, social, and environmental factors associated with sedentary behavior and physical inactivity among the Reunion Island adult population, and to highlight these findings in order to propose T2D primary prevention strategies aiming at alleviating local social inequalities in health (SIH). In 2021, we conducted a population-based cross-sectional telephone survey using random sampling. Participants included adults over 15 years old living in ordinary accommodation on Reunion Island (n = 2,010). Using a sequential approach, multinomial logistic regression model (explaining 3 profiles of interest: sedentary/inactive, sedentary/active, non-sedentary/inactive), and sampling-design weighted estimates, we found that 53.9% [95% confidence interval: 51.1 to 56.7%] of participants had sedentary behavior and 20.1% [95% CI: 17.8 to 22.5%] were inactive. Abandoning physical activity due to the COVID-19 pandemic (p<0.001), final secondary school diploma or above (p = 0.005), student as professional status (p≤0.005) and living in fewer poor neighborhoods located far from city centers (p = 0.030) were four conditions independently associated with sedentary/inactive and/or sedentary/active profiles. Based on these findings, to help reduce SIH, we used a typology of actions based on the underlying theoretical interventions including four main action categories: strengthening individuals (using person-based strategies), strengthening communities, improving living and working conditions, and promoting health-based macro-policies. Our findings suggest several directions for reducing lifestyle risk factors and enhancing T2D primary prevention programs targeting psychosocial, behavioral, and structural exposures.

Coenzyme Q10 (CoQ10) supplementation appears to be associated with a lower blood pressure. Nevertheless, it remains unclear whether food-sourced CoQ10 will affect new-onset hypertension in general adults. This study investigated the relationship between dietary CoQ10 intake and new-onset hypertension among the general population. Participants without hypertension at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort study were included (n = 11,428). Dietary CoQ10 intake was collected by validated dietary recalls and the food weighing method. Linear and non-linear relationships between dietary CoQ10 intake and new-onset hypertension were analyzed using multivariable Cox proportional hazards models and restricted cubic splines. During follow-up (median: 6 years), 4006 new-onset hypertension cases were documented. Compared with non-consumers, the hazard ratio (HR) and 95% confidence interval (CI) from quintile 2 to 4 total dietary CoQ10 were 0.83 (0.76, 0.91), 0.86 (0.78, 0.94) and 1.01 (0.92, 1.11); total plant-derived CoQ10 were 0.80 (0.73, 0.88), 1.00 (0.91, 1.09) and 1.10 (1.00, 1.20); and animal-derived CoQ10 were 0.65 (0.59, 0.71), 0.58 (0.53, 0.64) and 0.68 (0.62, 0.75). The lowest risk was found at moderate intake, with a non-linear relationship (P nonlinearity < 0.05). Furthermore, the overall inverse association was stronger among individuals without alcohol consumption or eating a low-fat diet. Moderate long-term dietary CoQ10 intake might be protective against new-onset hypertension. However, it follows a non-linear relationship and excessive intake may increase the risk of new-onset hypertension in the Chinese population.

UNASSIGNED: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population.
UNASSIGNED: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol.
UNASSIGNED: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%-21.9%), thus preventing an estimated 113 thousand (95% CI: 83-138) hard ASCVD events for Chinese adults aged 30-79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs.
UNASSIGNED: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population.
UNASSIGNED: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

UNASSIGNED: The MI-GENES clinical trial (NCT01936675), in which participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (FRSg, n=103), or an integrated risk score (IRSg, n=104) that additionally included a polygenic risk score (PRS), demonstrated that after 6 months, participants randomized to IRSg had higher statin initiation and lower low-density lipoprotein cholesterol (LDL-C).
UNASSIGNED: In a post hoc 10-year follow-up analysis of the MI-GENES trial, we investigated whether disclosure of a PRS for CHD was associated with a reduction in adverse cardiovascular events.
UNASSIGNED: Participants were followed from randomization beginning in October 2013 until September 2023 to ascertain adverse cardiovascular events, testing for CHD, and changes in risk factors, by blinded review of electronic health records. The primary outcome was the time from randomization to the occurrence of the first major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and non-fatal stroke. Statistical analyses were conducted using Cox proportional hazards regression and linear mixed-effects models.
UNASSIGNED: We followed all 203 participants who completed the MI-GENES trial, 100 in FRSg and 103 in IRSg (mean age at the end of follow-up: 68.2±5.2, 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in FRSg and 2 in IRSg (hazard ratio (HR), 0.20; 95% confidence interval (CI), 0.04 to 0.94; P=0.042). In FRSg, 47 (47%) underwent at least one test for CHD, compared to 30 (29%) in IRSg (HR, 0.51; 95% CI, 0.32 to 0.81; P=0.004). IRSg participants had a longer duration of statin therapy during the first four years post-randomization and a greater reduction in LDL-C for up to 3 years post-randomization. No significant differences between the two groups were observed for hemoglobin A1C, systolic and diastolic blood pressures, weight, and smoking cessation rate during follow-up.
UNASSIGNED: The disclosure of an IRS that included a PRS to individuals at intermediate risk for CHD was associated with a lower incidence of MACE after a decade of follow-up, likely due to a higher rate of initiation and longer duration of statin therapy, leading to lower LDL-C levels.

UNASSIGNED: Cardiovascular disease (CVD) is a major concern of morbidity and mortality among cancer survivors. However, few evidence exists on the short- and long-term risk of CVD in kidney cancer (KCa) survivors.
UNASSIGNED: In this nationwide, large population-based retrospective cohort study, we used the Korean national health insurance and medical checkup survey linkage database (2007-2021), drawn from the entire Korean population. We included adults diagnosed with KCa as the first primary cancer and matched them to an individual without KCa at a 1:5 ratio. The primary outcome was CVD incidence, including myocardial infarction, stroke, atrial fibrillation, heart failure, peripheral arterial occlusion, and venous thromboembolism (VTE). We evaluated CVD risk at 6 months, 1 year, and 5 years following cancer diagnosis, using Fine-Gray competing risk models that accounted for death as a competing factor.
UNASSIGNED: A total of 149,232 participants were included (KCa survivors: N=20,093 and matched non-KCa individuals: N=129,139). After 6-month follow-up, KCa survivors showed an increased risk of CVD compared to the general population (subdistribution hazard ratio (HR) 2.70, 95% confidence interval (CI) 2.31-3.15). After 1 year, KCa survivors had a higher risk of CVD (HR=1.77, 95% CI: 1.56-2.00). After 5 years, this elevated CVD risk remained (HR=1.10, 95% CI: 1.03-1.18), with VTE identified as the primary contributing disease (HR=3.05, 95% CI:2.59-3.59).
UNASSIGNED: KCa survivors had an increased risk of CVD up to 5 years after cancer diagnosis compared to the general population. Our findings emphasize the importance of comprehensive healthcare management for both CVD and KCa throughout cancer survivorship.

OBJECTIVE: To external validate the SCORE2, AHA/ACC Pooled Cohort Equation (PCE), Framingham Risk Score (FRS), Non-Laboratory INTERHEART Risk Score (NL-IHRS), Globorisk-LAC, and WHO prediction models and compare their discrimination and calibration capacity.
METHODS: Validation in individuals aged 40-69 years with at least 10 years follow-up and without baseline use of statins or cardiovascular diseases from the Prospective Urban Rural Epidemiology prospective cohort study (PURE)-Colombia. For discrimination, the C-statistic, and Receiver Operating Characteristic curves with the integrated area under the curve (AUCi) were used and compared. For calibration, the smoothed time-to-event method was used, choosing a recalibration factor based on the integrated calibration index (ICI). In the NL-IHRS, linear regressions were used.
RESULTS: In 3,802 participants (59.1% women), baseline risk ranged from 4.8% (SCORE2 women) to 55.7% (NL-IHRS). After a mean follow-up of 13.2 years, 234 events were reported (4.8 cases per 1000 person-years). The C-statistic ranged between 0.637 (0.601-0.672) in NL-IHRS and 0.767 (0.657-0.877) in AHA/ACC PCE. Discrimination was similar between AUCi. In women, higher overprediction was observed in the Globorisk-LAC (61%) and WHO (59%). In men, higher overprediction was observed in FRS (72%) and AHA/ACC PCE (71%). Overestimations were corrected after multiplying by a factor derived from the ICI.
CONCLUSIONS: Six prediction models had a similar discrimination capacity, supporting their use after multiplying by a correction factor. If blood tests are unavailable, NL-IHRS is a reasonable option. Our results suggest that these models could be used in other countries of Latin America after correcting the overestimations with a multiplying factor.
Detecting people at high risk of cardiovascular disease and implementing preventive interventions in this population is a key strategy in primary prevention. Recently, new risk calculation tools have been developed, but before their application and routine use in populations different from those where it was developed, it\'s necessary to validate them. The recommendations for predicting cardiovascular risk in Colombia\'s guidelines are based on studies with noteworthy limitations. This study involving 3,802 healthy individuals in Colombia supports the recommendation of using these prediction models. The estimation result should be multiplied by a correction factor, because most of the prediction models overestimate cardiovascular risk. For example, the correction factors suggested in women for AHA/ACC PCE and SCORE2 are 0.54 and 0.75, respectively. In men, the correction factors suggested in AHA/ACC PCE and SCORE2 are 0.28 and 0.61, respectively. Therefore, the present study with a contemporary population provides additional evidence to update these recommendations in Colombia and perhaps in Latin America.