Comparative Discrimination of Life's Simple 7 and Life's Essential 8 to Stratify Cardiovascular Risk: Is the Added Complexity Worth It?

BACKGROUND: Life's Simple 7 (LS7) is an easily calculated and interpreted metric of cardiovascular health based on 7 domains: smoking, diet, physical activity, body mass index, blood pressure, cholesterol, and fasting glucose. The Life's Essential 8 (LE8) metric was subsequently introduced, adding sleep metrics and revisions of the previous 7 domains. Although calculating LE8 requires additional information, we hypothesized that it would be a more reliable index of cardiovascular health. METHODS: Both the LS7 and LE8 metrics yield scores with higher values indicating lower risk. These were calculated among 11 609 Black and White participants free of baseline cardiovascular disease (CVD) in the Reasons for Geographic and Racial Differences in Stroke study, enrolled in 2003 to 2007, and followed for a median of 13 years. Differences in 10-year risk of incident CVD (coronary heart disease or stroke) were calculated as a function LS7, and LE8 scores were calculated using Kaplan-Meier and proportional hazards analyses. Differences in incident CVD discrimination were quantified by difference in the c-statistic. RESULTS: For both LS7 and LE8, the 10-year risk was approximately 5% for participants around the 99th percentile of scores, and a 4× higher 20% risk for participants around the first percentile. Comparing LS7 to LE8, 10-year risk was nearly identical for individuals at the same relative position in score distribution. For example, the "cluster" of 2013 participants with an LS7 score of 7 was at the 35.8th percentile in distribution of LS7 scores, and had an estimated 10-year CVD risk of 8.4% (95% CI, 7.2%-9.8%). In a similar location in the LE8 distribution, the 1457 participants with an LE8 score of 60±2.5 at the 39.4th percentile of LE8 scores had a 10-year risk of CVD of 8.5% (95% CI, 7.1%-10.1%), similar to the cluster defined by LS7. The age-race-sex adjusted c-statistic of the LS7 model was 0.691 (95% CI, 0.667-0.705), and 0.695 for LE8 (95% CI, 0.681-0.709) (P for difference, 0.12). CONCLUSIONS: Both LS7 and LE8 were associated with incident CVD, with discrimination of the 2 indices practically indistinguishable. As a simpler metric, LS7 may be favored for use by the general population and clinicians.

2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery. METHODS: A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.

Machine Learning-Assisted Analysis of Sublingual Microcirculatory Dysfunction for Early Cardiovascular Risk Evaluation and Cardiovascular-Kidney-Metabolic Syndrome Stage in Patients With Type 2 Diabetes Mellitus.

AIMS: To examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This cross-sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular-kidney-metabolic (CKM) syndrome stage. Side-stream dark-field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine-learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points. RESULTS: Compared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (ba-PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DMSA screen), and cut-off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA. CONCLUSIONS: Sublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM.

Advanced glycation end products are associated with cardiovascular risk in the Mexican population.

BACKGROUND AND AIMS: Chronic exposure to hyperglycemia is a significant risk factor for cardiovascular disease (CVD). Advanced glycation end products (AGES) result from multiple sugar-dependent reactions interacting with proteins and their receptors, generating endothelial dysfunction and CVD. However, there is little epidemiological data about its impact on CVD risk. We aimed to assess the association between circulating AGES and CVD risk in the Mexican population. METHODS AND RESULTS: We used longitudinal data from waves 2004-2006 and 2010-2012 of 1195 participants from the Health Workers Cohort Study. Circulating AGES were assessed by radioimmunoassay, and cardiovascular risk (CVR) was computed with the Framingham risk score. Linear and logistic fixed-effects regression models were used to assess the interest association, adjusting for confounding factors. An increase in 200 µU/ml of AGES was associated with a 0.18% increased risk of CVD (95% CI 0.05-0.31%). After adjusting for physical activity and smoking status, individuals who increased their AGES category had higher odds of middle-high CVR (low to medium AGES: OR 1.83, 95% CI 1.11-3.20; low to high AGES: OR 2.61, 95% CI 1.51-4.50). The associations remained statistically significant when we further adjusted for insulin resistance, dietary intake of AGES, and total daily calorie intake. CONCLUSION: Our data show that circulating AGES are associated with the Framingham CVD risk score, independently of other major risk factors for CVD in the Mexican population.

Validation of the Framingham General Cardiovascular Risk Score and Pooled Cohort Equations in a Community-Based Population: A Prospective Cohort Study Analysis 2006-2017.

Background: The 10-year atherosclerotic cardiovascular disease (ASCVD) risk - as assessed using the Framingham general cardiovascular risk score (FRS-CVD) or pooled cohort equations (PCE) - is commonly used in Western cohorts for the primary prevention of cardiovascular disease (CVD). However, the FRS-CVD and PCE have not been validated in Taiwanese cohorts. Objectives: We aimed to validate the FRS-CVD and PCE for assessing the 10-year ASCVD risk using a Taiwanese community-based population. Methods: We extracted patient data from the Landseed Integrated Outreaching Neighborhood Screening registry, a community-based prospective cohort study established in 2006. Cardiovascular events from 2006 to 2017 were determined from electronic medical records. The discriminative power and calibration of the FRS-CVD and PCE were evaluated. Results: Overall, 5,139 subjects were analyzed; the 10-year follow-up rate was 99.6%. The mean age at baseline was 52.8 ± 13.1 years, and 44.6% of the subjects were male. In total, 430 of 4,631 (9.3%) and 227 of 4,022 (5.6%) of the FRS-CVD- and PCE-like cohorts, respectively, had ASCVD events. The calibration χ2 of the FRS-CVD was 7.0267 (p = 0.6343) in males and 7.8845 (p = 0.5458) in females; the χ2 of PCE was 13.007 (p = 0.1623) in males and 38.785 (p < 0.001) in females. The area under the receiver operating characteristic curve (AUROC) of the FRS-CVD was 0.76 (0.72-0.79) in males and 0.71 (0.67-0.74) in females; the AUROC of PCE was 0.68 (0.62-0.73) in males and 0.61 (0.56-0.67) in females. Conclusions: Except for PCE in females, the FRS-CVD and PCE provided good calibration and modest discrimination in statin-naïve Taiwanese individuals without prior CVD.

The trend of 10-year cardiovascular risk among diabetic and non-diabetic participants in Tehran Lipid and glucose study: 1999-2018.

BACKGROUND: Assessing the risk of cardiovascular disease (CVD) is crucial in preventive cardiology. We aimed to determine the trend of CVD risk among individuals with and without diabetes during two decades of follow-up in a Middle Eastern cohort. METHODS: We studied 8,450 individuals (55.5% women) aged 40-75 years who participated in the Tehran Lipid and Glucose Study (TLGS). Diabetes status and CVD risk factors were evaluated in six examinations from 1999 to 2018. The individual 10-year CVD risk score was calculated using the ACC/AHA recommended risk equation. We used generalized estimating equation models (GEE) to assess the time trends of CVD risk factors and CVD risk scores in diabetic and non-diabetic groups separately. RESULTS: The age-adjusted ACC/AHA risk score significantly decreased in non-diabetic women and men (from 3.2% to 1.6% in women and 6.8% to 5.0% in men; p for trend < 0.001). Whereas the risk significantly decreased among diabetics men (from 13.8% to 11.5%), it increased somehow among diabetics women (from 5.3% to 5.5%). Furthermore, in both sexes, diabetic individuals compared to non-diabetic ones had better control on their systolic blood pressure, total cholesterol, and fasting plasma glucose during the last two decades. CONCLUSIONS: The CVD risk and most CVD risk factors improved in individuals with and without diabetes in the past two decades; however, they have not reached the targets yet. So, more stringent lifestyle modifications and treatment strategies are needed, especially for primary prevention in the general population.

Trajectories of cardiovascular disease risk and their association with the incidence of cardiovascular events over 18 years of follow-up: The Tehran Lipid and Glucose study.

BACKGROUND: Understanding long-term patterns (trajectories) of cardiovascular diseases (CVD) risk and identifying different sub-groups with the same underlying risk patterns could help facilitate targeted cardiovascular prevention programs. METHODS: A total of 3699 participants of the Tehran Lipid and Glucose Study (TLGS) (43% men, mean age = 53.2 years), free of CVD at baseline in 1999-2001 and attending at least one re-examination cycle between the second (2002-2005) and fourth cycles (2009-2011) were included. We examined trajectories of CVD risk, based on the ACC/AHA pooled cohort equation, over ten years and subsequent risks of incident CVD during eight years later. We estimated trajectories of CVD risk using group-based trajectory modeling. The prospective association of identified trajectories with CVD was examined using Cox proportional hazard model. RESULTS: Three distinct trajectories were identified (low-low, medium-medium, and high-high risk). The high-high and medium-medium CVD risk trajectories had an increasing trend of risk during the time; still, this rising trend was disappeared after removing the effect of increasing age. Upon a median 8.4 years follow-up, 146 CVD events occurred. After adjusting for age, the medium-medium and high-high trajectories had a 2.4-fold (95% CI 1.46-3.97) and 3.46-fold (95% CI 1.56-7.70) risk of CVD compared with the low-low group, respectively. In all trajectory groups, unfavorable increasing in fasting glucose, but favorable raising in HDL and decreasing smoking and total cholesterol happened over time. CONCLUSIONS: Although the risk trajectories were stable during the time, different risk factors varied differently in each trajectory. These findings emphasize the importance of attention to each risk factor separately and implementing preventive strategies that optimize CVD risk factors besides the CVD risk.

The association between cardiovascular risk burden and cognitive function amongst the old: a 9-year longitudinal cohort study.

BACKGROUND AND PURPOSE: Cardiovascular risk burden in midlife has been linked to cognitive decline in later life, but whether this association still exists in older cohorts is unclear. METHODS: The association between the cardiovascular risk score and cognitive function was investigated using 9-year follow-up data. The risk score algorithms were from the Chinese guidelines on the prevention and treatment of dyslipidemia in adults (2016 revised), which were assessed at baseline and categorized into tertiles (low, middle and high). Full intelligence quotient (FIQ), verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) were assessed at follow-ups with the Wechsler Adult Intelligence Scale-Chinese, revised (WAIS-RC). Data were analyzed using the linear mixed-effects model. RESULTS: A total of 924 participants (mean age 78.06 ± 7.58 years) were included in our study. In all participants, the risk score ranged from 0.02 to 0.55 (mean score 0.16 ± 0.08). Compared with the low tertile, a higher risk score was associated with lower FIQ (ß -0.094, 95% confidence interval [CI] -0.181, -0.007) and VIQ (ß -0.100; 95% CI -0.192, -0.007) at the follow-up. There is a more significant association between higher risk score and lower FIQ amongst females (ß -0.263; 95% CI -0.462, -0.065) and VIQ (ß -0.268; 95% CI -0.478, -0.057). CONCLUSIONS: A higher cardiovascular risk score was associated with lower FIQ and VIQ. Higher cardiovascular risk burden increased the risk of cognition impairment and accelerated its progression over time. This study has implications for early detection of cognition impairment.

Association of cardiovascular risk burden with risk of dementia and brain pathologies: A population-based cohort study.

INTRODUCTION: The impact of cardiovascular risk burden on brain pathologies remains unclear. We aimed to examine the association of the Framingham General Cardiovascular Risk Score (FGCRS) with dementia risk, and brain pathologies. METHODS: Within the Rush Memory and Aging Project, 1588 dementia-free participants were assessed on FGCRS at baseline and followed up to 21 years. During the follow-up, 621 participants died and underwent autopsies. RESULTS: The multi-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of FGCRS were 1.03 (1.00-1.07) for dementia and 1.04 (1.01-1.07) for Alzheimer's disease (AD) dementia. Further, a higher FGCRS was associated with higher gross chronic cerebral infarctions (odds ratio [OR] 1.08, 95% CI 1.02-1.14), cerebral atherosclerosis (OR 1.10, 95% CI 1.03-1.17), and global AD pathology (OR 1.06, 95% CI 1.01-1.12). CONCLUSIONS: A higher FGCRS is associated with an increased risk of dementia and AD dementia. Both vascular and AD pathologies in the brain may underlie this association.

Prevalence of Asymptomatic Coronary Heart Disease in the Siblings of Young Myocardial Infarction Patients as Detected by Coronary Computer Tomography Angiography: A Pilot Study.

BACKGROUND: There is little data on the prevalence of coronary heart disease (CHD) in the young. The study aimed to estimate the prevalence of asymptomatic CHD in siblings of young patients with myocardial infarction (MI) using coronary computed tomography angiography (CCTA). METHODS: Prospective observational data was collected on siblings of patients aged ≤55 years presenting with acute MI and having coronary stenosis ≥50% on invasive coronary angiography in at least one epicardial coronary artery. Inclusion criteria included ages 30-55 and 30-60 years for males and females respectively. Outcome of interest was obstructive CHD by coronary computer tomography angiography (CCTA), which was defined by either moderate (50-69% stenosis) and/or severe (≥70% stenosis). RESULTS: Fifty participants were studied of whom 20 (40%) were male. Thirty (60%) were current or ex-smokers, 4 (8%) had diabetes, 8 (16%) had hypertension and 26 (52%) had dyslipidaemia. Obstructive CHD by CCTA was detected in 9 (18%, 95% CI 9%-31%) participants and 3 (6%, 95% CI 1%-17%) participants were found to have severe luminal stenosis. The median radiation dose was 3.9 (IQR 0.9) mSv. CONCLUSIONS: Approximately a fifth of siblings of young MI patients were found to have asymptomatic but obstructive CHD detected on CCTA of which one third was severe. This is a group in whom screening for CHD warrants further investigation.

Cardiorenal Determinants of Erectile Dysfunction in Primary Prevention: A Cross-Sectional Study.

OBJECTIVE: The aim of this study was to investigate the association between the severity of erectile dysfunction (ED), cardiovascular risk, and target organ damage (heart, renal, vascular) in men free of cardiovascular diseases (CVD). SUBJECTS AND METHODS: ED was assessed using the International Index of Erectile Function (IIEF-5). The study included 182 men: 100 with ED (IIEF mean score ≤21) and 82 without ED (IIEF mean score >21). Ultrasound was used to evaluate carotid plaques and left ventricular mass, geometry, and diastolic function. Cardiovascular anamnesis, CVD risk factors, and anthropometric and biochemical parameters were obtained. The European Society of Cardiology-Systematic Coronary Risk Evaluation Score (ESC-SCORE) was used to calculate total patient cardiovascular risk. Continuous variables between groups were compared using the Student t test and Mann-Whitney U test, while categorical data were compared using the χ2 test. Multiple linear regression was used to test the association between the severity of ED and presence of target organ damage. RESULTS: The following parameters were significantly higher in the ED group compared to the controls: family history of coronary heart disease (43.7 vs. 26.7%, p = 0.047), ESC-SCORE (2.27 ± 1.79 vs. 1.61 ± 1.13, p = 0.012), and waist circumference (109.28 ± 10.82 vs. 106.17 ± 10.07, p = 0.047). Impaired renal function (p = 0.081), albuminuria (p = 0.545), vascular damage (p = 0.602), and diastolic function (p = 0.724) were similar in both groups. However, left ventricular hypertrophy (LVH; odds ratio 2.231, 95% CI 1.069-4.655, p = 0.22) was more frequent in the ED group (29.9 vs. 16.0%). The multiple linear regression analysis revealed that LVH (ß = 1.761, p = 0.002) and impaired renal function assessed using the estimated glomerular filtration rate (<60 mL/min/1.73 m2; ß = 6.207, p = 0.0001) were the independent risk factors for severity of ED. CONCLUSION: This study showed that LVH and impaired renal function are associated with ED severity.

Mixed brain lesions mediate the association between cardiovascular risk burden and cognitive decline in old age: A population-based study.

INTRODUCTION: The underlying pathological mechanisms linking cardiovascular burden to cognitive decline remain unclear. METHODS: We investigated the associations of the Framingham general cardiovascular risk score (FGCRS), apolipoprotein E (APOE) ε4, and brain structure with the Mini-Mental State Examination (MMSE) decline using the 9-year follow-up data from Swedish National Study on Aging and Care in Kungsholmen (n = 2189, age ≥60) and the embedded magnetic resonance imaging (MRI) (n = 448) studies. Volumes of white matter hyperintensities (WMHs), total gray matter, ventricles, and hippocampus were assessed in the MRI sample. RESULTS: A higher FGCRS was associated with faster MMSE decline in young-old people (60-72 years) but not in old-old (≥78 years). Larger volumes of cerebral WMHs and ventricles and smaller volumes of total gray matter and hippocampus were all associated with accelerated MMSE decline (P < .01); these associations were stronger among APOE ε4 carriers than noncarriers. Simultaneously entering multiple brain lesion markers as mediators in the model substantially attenuated the association between FGCRS and MMSE decline. DISCUSSION: The effect of cardiovascular risk burden on cognitive deterioration in old age is largely mediated by mixed brain lesions.

Child Marriage and Cardiovascular Risk: An Application of the Non-laboratory Framingham Risk Score.

INTRODUCTION: Child marriage, defined as marriage before the age of 18 years, is a precocious transition from adolescence to adulthood, which may take a long-term toll on health. AIM: This study aims to assess whether child marriage was associated with added risk of adverse cardiovascular outcomes in a nationally representative sample of Indian adults. METHODS: Applying the non-laboratory-based Framingham algorithm to data on 336,953 women aged 30-49 years and 49,617 men aged 30-54 years, we estimated individual's predicted heart age (PHA). Comparing the PHA with chronological age (CA), we categorized individuals in four groups: (i) low PHA: PHA < CA, (ii) equal PHA: PHA = CA (reference category), (iii) high PHA: PHA > CA by at most 4 years, and (iv) very high PHA: PHA > CA by 5 + years. We estimated multivariable multinomial logistic regressions to obtain relative risks of respective categories for the child marriage indicator. RESULTS: We found that women who were married in childhood had 1.06 (95% CI 1.01-1.10) and 1.22 (95% CI 1.16-1.27) times higher adjusted risks of having high and very high PHA, respectively, compared to women who were married as adults. For men, no differential risks were found between those who were married as children and as adults. These results were generally robust across various socioeconomic sub-groups. CONCLUSIONS: These findings add to the relatively new and evolving strand of literature that examines the role of child marriage on later life chronic health outcomes and provide important insights for public health policies aimed at improving women's health and wellbeing.

Association between cardiovascular risk profile and impaired microvascular function in a Swedish middle-aged cohort (the SCAPIS study).

AIMS: The aim was to investigate the relationship between microvascular function, cardiovascular risk profile, and subclinical atherosclerotic burden. METHODS AND RESULTS: The study enrolled 3809 individuals, 50-65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study. Microvascular function was assessed in forearm skin using an arterial occlusion and release protocol determining peak blood oxygen saturation (OxyP). Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation [SCORE2; 10-year risk of fatal and non-fatal cardiovascular disease (CVD) events]. The OxyP was compared with coronary artery calcification score (CACS) and to plaques in the carotid arteries. Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function) had a mean SCORE2 of 5.8% compared with 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. The risk of having a SCORE2 > 10% was five times higher for those in Q1 (odds ratio: 4.96, 95% confidence interval: 2.76-8.93) vs. Q4 when adjusting for body mass index and high-sensitivity C-reactive protein. The OxyP was lower in individuals with CACS > 0 and in those with both carotid plaques and CACS > 0, compared with individuals without subclinical atherosclerotic burdens (87.5 ± 5.6% and 86.9 ± 6.0%, vs. 88.6 ± 5.8%, P < 0.01). CONCLUSION: In a population without CVD or diabetes mellitus, impaired microvascular function is associated with cardiovascular risk profiles such as higher SCORE2 risk and CACS. We suggest that OxyP may serve as a microcirculatory functional marker of subclinical atherosclerosis and CVD risk that is not detected by structural assessments.

Impaired microvascular function was associated with higher cardiovascular risk profile SCORE2 and subclinical atherosclerotic burden defined by carotid plaque and coronary artery calcification score (CACS).Individuals with impaired microvascular function (peak oxygen saturation in the forearm skin, OxyP, after a prolonged arterial occlusion provocation) had a moderate risk level of SCORE2 compared to low risk level in those with the highest values of OxyP.The OxyP was lower in individuals with CACS > 0 and in those with both carotid plaques and CACS > 0, compared with individuals with carotid plaque only and in individuals without subclinical atherosclerotic burdens.

Assessment of osteoprotegerin and RANKL levels and several cardiovascular risk scoring systems in acromegaly.

PURPOSE: The OPG/RANKL (osteoprotegerin/receptor activator of nuclear factor kappa-B) system, which plays a crucial role in bone metabolism, is also associated with vascular calcification. Acromegaly is characterized by excessive secretion of growth hormone and insulin-like growth factor, and studies have demonstrated an elevated risk of cardiovascular disease in individuals with acromegaly. In this study, our objective was to investigate the relationship between OPG/RANKL and various cardiovascular risk scoring systems. METHODS: We recruited 44 consecutive acromegaly patients and 41 healthy controls with a similar age and gender distribution for this study. RESULTS: While RANKL levels were significantly higher in the acromegaly group compared to the controls, OPG levels were not found to be significantly different between the two groups. Furthermore, within the acromegaly group, RANKL levels were significantly higher in patients with active acromegaly compared to those with controlled acromegaly. Osteoprotegerin levels showed a positive correlation with the Framingham risk score (FRS) in the acromegaly group. Linear regression analysis revealed an association of OPG with FRS (adjusted R2 value of 21.7%). CONCLUSION: OPG and RANKL may serve as potential markers for assessment of cardiovascular calcification and prediction of the cardiovascular risk status in acromegalic patients.

Cardiovascular risk of dementia is associated with brain-behaviour changes in cognitively healthy, middle-aged individuals.

Alzheimer's Disease (AD) neuropathology start decades before clinical manifestations, but whether risk factors are associated with early cognitive and brain changes in midlife remains poorly understood. We examined whether AD risk factors were associated with cognition and functional connectivity (FC) between the Locus Coeruleus (LC) and hippocampus - two key brain structures in AD neuropathology - cross-sectionally and longitudinally in cognitively healthy midlife individuals. Neuropsychological assessments and functional Magnetic Resonance Imaging were obtained at baseline (N=210), and two-years follow-up (N=188). Associations of cognition and FC with apolipoprotein ε4 (APOE ε4) genotype, family history of dementia, and the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score were investigated. Cross-sectionally, higher CAIDE scores were associated with worse cognition. Menopausal status interacted with the CAIDE risk on cognition. Furthermore, the CAIDE score significantly moderated the relationship between cognition and LC-Hippocampus FC. Longitudinally, the LC-Hippocampus FC decreased significantly over 2 years. These results suggest that cardiovascular risk of dementia is associated with brain-behaviour changes in cognitively healthy, middle-aged individuals.

Comparison of Four Predictive Scores for Cardiovascular Risk in Mexican People with HIV.

Persons with HIV (PWH) face an increased risk of cardiovascular events due to immune activation, comorbidities, and certain antiretrovirals (ARVs). However, the current cardiovascular risk (CVR) scores are not specifically directed toward PWH. This study aimed to assess the agreement between different predictive CVR scores and explore their relationship with clinical and demographic data in Mexican PWH. A descriptive cross-sectional analysis was conducted in 200 PWH with a mean age of 42 years who were treated at a Mexican urban center from 2017 to 2018. The majority (83%) was on ARV treatment and 79.5% had undetectable viral loads (VLs). Moderate- to high-risk scores were infrequent, with Framingham Risk Score for Hard Coronary Heart Disease scores showing higher values, with very low concordance among all scores. Logistic regression analysis revealed significant associations between the CVR scores and the initial recorded VL, CD4 cell count, and elevated triglyceride levels. However, no associations were found with measures such as body mass index or abdominal circumference. Treatment with integrase strand transfer inhibitors (INSTIs), particularly first-generation inhibitors, showed strong associations with all predictive scores, notably ASCVD (odds ratio = 7.03, 95% confidence interval 1.67-29.64). The poor concordance among the CVR scores in PWH highlights the need for a specific score that considers comorbidities and ARV drugs. Despite the relatively young age of the participants, significant correlations were observed between INSTI use, initial VL, CD4 cell count, and triglyceride levels, which are factors not considered in the existing risk scores. Regardless of the actual value of the scores, screening for CVR in PWH is recommended.

Urinary Epinephrine Sulfate Can Predict Cardiovascular Risk in Moderate-to-Severe OSA: A Metabolomics-Based Study.

Purpose: There are currently no ideal indicators for predicting the cardiovascular risk of obstructive sleep apnea (OSA). This study aimed to employ urinary metabolomics to detect early cardiovascular risk in patients with moderate-to-severe OSA. Patients and Methods: Male participants who underwent polysomnography from November 2020 to May 2021 were screened. Clinical data, polysomnography data and urine samples were collected. Untargeted metabolomics analyses of urine were performed. Multivariate analyses and receiver operating characteristic (ROC) curve analyses were subsequently performed to identify potential biomarkers. Associations between metabolites and clinical indicators and cardiovascular risk were examined through linear regression analyses with interaction and mediation analyses. Results: Thirty-six male participants were included in the study, comprising 22 males with moderate-to-severe OSA and 14 age-matched controls, with an average age of 39.6 ± 9.2 years. We identified 65 metabolites in the study, involving pathways including pyrimidine, androgen, estrogen, vitamin B6 and sulfate/sulfite metabolism. Among them, epinephrine sulfate was the most significantly altered metabolite. ROC analyses highlighted that epinephrine sulfate had the highest area under the curve (AUC=0.883) for detecting moderate-to-severe OSA. Epinephrine sulfate was statistically correlated with OSA severity, hypoxia-related indicators (apnea-hypopnea index: r=0.685; oxygen desaturation index: r=0.743, p<0.0001), arterial stiffness (arterial augmentation index: r=0.361, p=0.031) and long-term cardiovascular risk (Framingham cardiovascular risk: r=0.375, p=0.024). Linear regression analysis revealed that epinephrine sulfate was significantly associated with an increased in the Framingham risk (ß = 0.004, 95% CI = 0.000-0.009, p = 0.049), with the effect partly mediated by systolic blood pressure (27.6%) and not moderated by other factors. Additionally, it also significantly associated with the increased in the arterial augmentation index (ß = 0.019, 95% CI = 0.000-0.037, p = 0.046), with the effect fully mediated by blood pressure and not moderated by other indices statistically. Conclusion: There are significant metabolic pathway alterations in moderate-to-severe OSA patients. Urinary epinephrine sulfate markedly predicts early cardiovascular risk in OSA patients.

Predictive Performance of Cardiovascular Risk Scores in Cancer Survivors From the UK Biobank.

Background: Cardiovascular preventive strategies are guided by risk scores with unknown validity in cancer cohorts. Objectives: This study aimed to evaluate the predictive performance of 7 established cardiovascular risk scores in cancer survivors from the UK Biobank. Methods: The predictive performance of QRISK3, Systematic Coronary Risk Evaluation 2 (SCORE2)/Systematic Coronary Risk Evaluation for Older Persons (SCORE-OP), Framingham Risk Score, Pooled Cohort equations to Prevent Heart Failure (PCP-HF), CHARGE-AF, QStroke, and CHA2DS2-VASc was calculated in participants with and without a history of cancer. Participants were propensity matched on age, sex, deprivation, health behaviors, family history, and metabolic conditions. Analyses were stratified into any cancer, breast, lung, prostate, brain/central nervous system, hematologic malignancies, Hodgkin lymphoma, and non-Hodgkin lymphoma. Incident cardiovascular events were tracked through health record linkage over 10 years of follow-up. The area under the receiver operating curve, balanced accuracy, and sensitivity were reported. Results: The analysis included 31,534 cancer survivors and 126,136 covariate-matched controls. Risk score distributions were near identical in cases and controls. Participants with any cancer had a significantly higher incidence of all cardiovascular outcomes than matched controls. Performance metrics were significantly worse for all risk scores in cancer cases than in matched controls. The most notable differences were among participants with a history of hematologic malignancies who had significantly higher outcome rates and poorer risk score performance than their matched controls. The performance of risk scores for predicting stroke in participants with brain/central nervous system cancer was very poor, with predictive accuracy more than 30% lower than noncancer controls. Conclusions: Existing cardiovascular risk scores have significantly worse predictive accuracy in cancer survivors compared with noncancer comparators, leading to an underestimation of risk in this cohort.

Circulating Metabolite Profiles and Risk of Coronary Heart Disease Among Racially and Geographically Diverse Populations.

BACKGROUND: Metabolomics may reveal novel biomarkers for coronary heart disease (CHD). We aimed to identify circulating metabolites and construct a metabolite risk score (MRS) associated with incident CHD among racially and geographically diverse populations. METHODS: Untargeted metabolomics was conducted using baseline plasma samples from 900 incident CHD cases and 900 age-/sex-/race-matched controls (300 pairs of Black Americans, White Americans, and Chinese adults, respectively), which detected 927 metabolites with known identities among ≥80% of samples. After quality control, 896 case-control pairs remained and were randomly divided into discovery (70%) and validation (30%) sets within each race. In the discovery set, conditional logistic regression and least absolute shrinkage and selection operator over 100 subsamples were applied to identify metabolites robustly associated with CHD risk and construct the MRS. The MRS-CHD association was evaluated using conditional logistic regression and the C-index. Mediation analysis was performed to examine if MRS mediated associations between conventional risk factors and incident CHD. The results from the validation set were presented as the main findings. RESULTS: Twenty-four metabolites selected in ≥90% of subsamples comprised the MRS, which was significantly associated with incident CHD (odds ratio per 1 SD, 2.21 [95% CI, 1.62-3.00] after adjusting for sociodemographics, lifestyles, family history, and metabolic health status). MRS could distinguish incident CHD cases from matched controls (C-index, 0.69 [95% CI, 0.63-0.74]) and improve CHD risk prediction when adding to conventional risk factors (C-index, 0.71 [95% CI, 0.65-0.76] versus 0.67 [95% CI, 0.61-0.73]; P<0.001). The odds ratios and C-index were similar across subgroups defined by race, sex, socioeconomic status, lifestyles, metabolic health, family history, and follow-up duration. The MRS mediated large portions (46.0%-74.2%) of the associations for body mass index, smoking, diabetes, hypertension, and dyslipidemia with incident CHD. CONCLUSIONS: In a diverse study sample, we identified 24 circulating metabolites that, when combined into an MRS, were robustly associated with incident CHD and modestly improved CHD risk prediction beyond conventional risk factors.