Role Of Cardiovascular Risk Factors Research Articles

Cardiovascular risk factors among older persons with cognitive frailty in middle income country

BACKGROUND Cognitive frailty, characterized by the coexistence of cognitive impairment and physical frailty, represents a multifaceted challenge in the aging population. The role of cardiovascular risk factors in this complex interplay is not yet fully understood. AIM To investigate the relationships between cardiovascular risk factors and older persons with cognitive frailty by pooling data from two cohorts of studies in Malaysia. METHODS A comprehensive approach was employed, with a total of 512 community-dwelling older persons aged 60 years and above, involving two cohorts of older persons from previous studies. Datasets related to cardiovascular risks, namely sociodemographic factors, and cardiovascular risk factors, including hypertension, diabetes, hypercholesterolemia, anthropometric characteristics and biochemical profiles, were pooled for analysis. Cognitive frailty was defined based on the Clinical Dementia Rating scale and Fried frailty score. Cardiovascular risk was determined using Framingham risk score. Statistical analyses were conducted using SPSS version 21. RESULTS Of the study participants, 46.3% exhibited cognitive frailty. Cardiovascular risk factors including hypertension (OR:1.60; 95%CI: 1.12-2.30), low fat-free mass (OR:0.96; 95%CI: 0.94-0.98), high percentage body fat (OR:1.04; 95%CI: 1.02-1.06), high waist circumference (OR:1.02; 95%CI: 1.01-1.04), high fasting blood glucose (OR:1.64; 95%CI: 1.11-2.43), high Framingham risk score (OR:1.65; 95%CI: 1.17-2.31), together with sociodemographic factors, i.e. , being single (OR 3.38; 95%CI: 2.26-5.05) and low household income (OR 2.18; 95%CI: 1.44-3.30) were found to be associated with cognitive frailty. CONCLUSION Cardiovascular-risk specific risk factors and sociodemographic factors were associated with risk of cognitive frailty, a prodromal stage of dementia. Early identification and management of cardiovascular risk factors, particularly among specific group of the population might mitigate the risk of cognitive frailty, hence preventing dementia.

The Impact of Cardiovascular Risk Factors on the Incidence, Severity, and Prognosis of Sudden Sensorineural Hearing Loss (SSHL): A Systematic Review.

Sudden sensorineural hearing loss (SSHL) is believed to be mainly idiopathic since the cause is not usually identified. Several recent studies have examined the role of cardiovascular risk factors in this disease.The aim of this systematic literature review is to investigate the possible association between acquired and inherited cardiovascular risk factors and the incidence, severity, and prognosis of SSHL. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the PubMed database for the period between February 2010 and January 2023 was performed in order to retrieve eligible articles. The analytic cohort included 24 studies. Overall, this systematic review includes a total of 61,060 patients that were encompassed in these studies. According to most studies, the prevalence of dyslipidaemia, diabetes, and ultrasound indices of atherosclerosis was significantly higher in SSHL patients compared to controls. On the other hand, obesity, hypertension, and smoking did not seem to influence the risk of SSHL. Most studies suggest the presence of a correlation between a high cardiovascular risk profile and the risk of developing SSHL. The theory of microvascular impairment in the development of SSHL is indirectly supported by the findings of this review.

LONGITUDINAL CHANGES IN PROTEOMIC BIOMARKERS IN ALZHEIMER’S DISEASE AND CARDIOVASCULAR DISEASE

Abstract Alzheimer’s disease (AD) and cardiovascular diseases (CVDs) commonly co-occur in older adults. This correlation prompts an investigation into the potential shared risk factors linking AD and CVDs, and the potential direct causative role of cardiovascular risk factors in AD. The cohort comprised 566 older adults including 111 individuals with AD, 58 without AD, 383 with mild cognitive impairment (MCI), 410 with CVD and 156 without CVD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The multivariable linear mixed model (LMM) was used to investigate the associations of AD and CVD on longitudinal changes of 146 proteomic biomarkers (measured at baseline and 12-month follow-up), while adjusted for age, gender, education, racial groups, and APOE-ε4 alleles. The LMM showed that AD and CVD were associated with longitudinal changes in 48 and 46 proteomic biomarkers, respectively (p< 0.05). Interestingly, both AD and CVD were associated with longitudinal changes in 14 proteomic biomarkers (A1Micro, ApoH, B2M, BNP, Complement C3, Cystatin C, KIM1, NGAL, PPP, TIM1, THP, TFF3, TM, and VEGF). Furthermore, the single biggest risk gene for sporadic AD, APOE-ε4 was associated with 22 proteomic biomarkers. Moreover, MCI and CVD were associated with 13 proteomic biomarkers (A1Micro, ApoD, AXL, BNP, Calcitonin, CD40, C-peptide, pM, PPP, THP, TNFR2, TTR, and VEGF), while MCI, CVD and APOE-ε4 were associated with four proteomic biomarkers (A1Micro, Calcitonin, THP, and TNFR2). This study provides valuable insights into the shared and distinct pathophysiological mechanisms at play, offering a stepping-stone towards a deeper comprehension of the interrelationship between AD and CVDs.

The Efficiency of Attentional Networks in Takostubo Syndrome: A Study With the Attentional Network Task for Interaction

Introduction: The role of cardiovascular risk factors in the occurrence and progression of cognitive impairment is relevant in aging studies. In this condition, attention is one of the processes less studied, but preliminary evidence suggests an association between cardiometabolic alterations and attentional decline. Attention is not a unitary process but a set of independent systems (Alerting, Orienting, Executive), which can interact in certain conditions to ensure maximum behavioral efficiency. Methods: We investigated attentive networks and their interactions in patients with Takostubo syndrome (TTS). In all, 20 participants with TTS and 20 individuals without cardiovascular pathologies performed an Attention-Network Task for Interaction, which assesses attentional networks and their interactions. Results: Patients with TTS showed an atypical orienting effect when compared to the control group. Moreover, only the control group exhibited an interaction between orienting and alerting. Conclusion: These findings establish the relevance of brain–heart interaction in identifying attentional impairment as a prodrome of progressively severe cognitive impairment in TTS.

Cognitively healthy Indians with higher Framingham Cardiovascular Risk Scores have higher WMH burden with lesser grey matter, white matter and hippocampal volumes

AbstractBackgroundIncreasing evidence indicates the important role of cardiovascular risk factors in dementia risk, particularly in Indians. It is known that cardiovascular risk factors tend to cluster together, and a widely used multivariable risk scoring is the Framingham Cardiovascular Risk Score (FRS). However, very little is known about the association between FRS and structural brain MRI parameters in cognitively healthy Indians.MethodBaseline clinical and brain MRI data of 487 cognitively healthy Indians (Clinical Dementia Rating score of ‘0’), who are part of two ongoing, large, aging cohort studies in India – Srinivaspura Aging, Neuro Senescence and COGnition study (SANSCOG) study (n = 200) and Tata Longitudinal Study of Aging (TLSA, n = 289) were utilized. FRS was calculated using clinical and blood biochemistry data, whereas brain MRI scans were performed on 3T MRI scanners. White matter hyperintensity (WMH) lesion segmentation was performed using Lesion Segmentation Toolbox (LST) and brain volumes (total grey matter, total white matter, 3rd ventricle, right and left hippocampus) were derived using FreeSurfer software and normalized according to total intracranial volumes of the respective subjects. Linear regression analysis was performed with FRS as independent variable and various structural MRI parameters as dependent variables. A p value of <0.05 was considered significant.ResultUrban subjects with higher FRS had significantly higher WMH volume (β = 0.00011, p<0.001, R2 = 0.130), lower grey matter (β = ‐0.00285, p<0.001, R2 = 0.206), white matter (β = ‐0.00180, p<0.001, R2 = 0.106), right hippocampal (β = ‐0.00004, p<0.001, R2 = 0.180), left hippocampal (β = ‐0.00003, p<0.001, R2 = 0.156) volumes and higher 3rd ventricle volumes (β = 0.00003, p<0.001, R2 = 0.150). Rural subjects higher FRS had lower grey matter (β = ‐0.00166, p<0.001, R2 = 0.118, white matter (β = ‐0.0011, p<0.001, R2 = 0.060), right hippocampal (β = ‐0.00002, p<0.001, R2 = 0.087), left hippocampal (β = ‐0.00002, p<0.001, R2 = 0.084) volumes and higher 3rd ventricle volumes (β = 0.00004, p<0.001, R2 = 0.264) but no significant association was seen with WMH volume.ConclusionThese findings indicate that cardiovascular risk is associated with structural brain changes in cognitively healthy Indians. Since cardiovascular risk can be reduced through cost‐effective community level strategies, such as lifestyle‐based interventions, promptly addressing this risk in Indians could be an important part of dementia prevention strategies.

Vascular contribution to the preclinical Alzheimer’s disease pathological changes: Insights from the EPAD cohort

AbstractBackgroundThe role of cardiovascular risk factors and cerebral small vessel disease (CSVD) on the sequences of Alzheimer’s Disease (AD) pathological events remains to be determined.MethodWe included 1592 non‐demented participants from EPAD‐LCS (Table‐1). Linear models were used to study associations between the Framingham score (FRS) and CSF‐Aß1‐42; CSVD indices (visual assessment for perivascular spaces [PVS] in the basal ganglia [BG] and centrum‐semiovale [CS], periventricular and deep white matter hyperintensities [WMHs], presence of lobar or deep cerebral microbleeds [CMBs], and lacunes, and quantification of global and lobar WMH volumes) and Aß1‐42 and p‐Tau181, including an interaction between CSVD indices and Aß1‐42 for the latter. Hippocampal volumes (HCV) were quantified using LEAP. Structural equation models (SEM) were used to assess the association between clinical variables as described in Figure‐1. Models were corrected for age, sex, site and multiple comparisons.ResultHigher FRS scores were associated with lower CSF Aß1‐42 (ß = ‐0.18; p<0.001) and higher P‐tau181 (ß = 0.21; p<0.001). Aß1‐42 was negatively associated with all CSVD markers (all p<0.001; Figure‐2). We found stronger association between Aß1‐42 and P‐tau181 in participants with higher Fazekas deep and periventricular (p‐interaction<0.005) scores, and higher regional WMH (all p‐interactions<0.005) volumes. Using SEM, the CSVD‐burden latent factor fully mediated the association between FRS and Aß1‐42 (indirect effect: ß = ‐0.03; p<0.001). Aß1‐42 did not significantly predict the CSVD‐burden latent factor. We observed a significant direct effect of Aß1‐42 on P‐tau181 levels (ß = ‐0.14; p<0.001) and HCV (ß = 0.06; p<0.05), and of P‐tau181 levels onto HCV (ß = ‐0.05; p<0.05). A significant indirect, but not direct, effect of the latent factor on both P‐tau181 (indirect effect: ß = 0.36; p < 0.05) and HCV (indirect effect: ß = ‐0.24; p < 0.05) through Aß1‐42 was observed.ConclusionExpression of cerebrovascular pathology fully mediates the effects of vascular risk factors on amyloid and accelerates manifestation of downstream biomarkers in the preclinical phases of AD, stressing the importance of vascular‐protective treatments.

Causal association of cardiovascular risk factors with Alzheimer’s disease

AbstractBackgroundAlzheimer’s Disease (AD) frequently coexist with cerebrovascular disease (CVD) and makes it difficult for researchers to delineate the two pathologies with available diagnostic criteria. Neuroimaging techniques, especially FDG‐PET can help differentiate the two pathologies based on the characteristic temporo‐parietal metabolic deficitsin AD and regional patchy deficits in CVD. Co‐occurrence of the both patterns can be seen in mixed cases.Existing literature supports a possible role for cardiovascular risk factors in AD pathogenesis. This study aims to determine whether cardiovascular risk factors have a causative association with typical AD pathogenesis or it has an association with mixed AD.MethodBaseline brain FDG‐PET images of participants with a diagnosis of AD from two large clinical trials of hydromethylthionine were classified into “typical AD” and “mixed” patterns through visual analysis. Causal association of independent variable age and dependent variables cardiovascular risk factors, White matter hyperintensities (WMH), AD subtypes and severity of cognitive impairment depicted with ADAS Cog scores were analysed using Structural equation modelling (SEM).ResultOut of a total 794 participants, 533 (67.1%) were classified as typical AD and 261 (32.8%) were classified as mixed. Overall, the people with a mixed pattern were significantly younger than the people with a typical AD pattern. Age significantly influenced cardiovascular risk factors, WMH and typical AD subtype. The severity of cognitive impairment was significantly influenced by cardiovascular risk factors, WMH and typical AD subtype. Interestingly, cardiovascular risk factors had a statistically significant positive influence on typical AD subtype in comparison to mixed.ConclusionIt is well known fact that the cardiovascular risk factors are commonly associated with cerebrovascular disease but contrary to our expectations cardiovascular risk factors have a causal association with typical AD.

Vascular contribution to the preclinical Alzheimer’s disease pathological changes: Insights from the EPAD cohort

AbstractBackgroundThe role of cardiovascular risk factors and cerebral small vessel disease (CSVD) on the sequences of Alzheimer’s Disease (AD) pathological events remains to be determined.MethodWe included 1592 non‐demented participants from EPAD‐LCS (Table‐1). Linear models were used to study associations between the Framingham score (FRS) and CSF‐Aβ1‐42; CSVD indices (visual assessment for perivascular spaces [PVS] in the basal ganglia [BG] and centrum‐semiovale [CS], periventricular and deep white matter hyperintensities [WMHs], presence of lobar or deep cerebral microbleeds [CMBs], and lacunes, and quantification of global and lobar WMH volumes) and Aβ1‐42 and p‐Tau181, including an interaction between CSVD indices and Aβ1‐42 for the latter. Hippocampal volumes (HCV) were quantified using LEAP. Structural equation models (SEM) were used to assess the association between clinical variables as described in Figure‐1. Models were corrected for age, sex, site and multiple comparisons.ResultHigher FRS scores were associated with lower CSF Aβ1‐42 (β = ‐0.18; p<0.001) and higher P‐tau181 (β = 0.21; p<0.001). Aβ1‐42 was negatively associated with all CSVD markers (all p<0.001; Figure‐2).We found stronger association between Aβ1‐42 and P‐tau181 in participants with higher Fazekas deep and periventricular (p‐interaction<0.005) scores, and higher regional WMH (all p‐interactions<0.005) volumes.Using SEM, the CSVD‐burden latent factor fully mediated the association between FRS and Aβ1‐42 (indirect effect: β = ‐0.03; p<0.001). Aβ1‐42 did not significantly predict the CSVD‐burden latent factor. We observed a significant direct effect of Aβ1‐42 on P‐tau181 levels (β = ‐0.14; p<0.001) and HCV (β = 0.06; p<0.05), and of P‐tau181 levels onto HCV (β = ‐0.05; p<0.05). A significant indirect, but not direct, effect of the latent factor on both P‐tau181 (indirect effect: β = 0.36; p < 0.05) and HCV (indirect effect: β = ‐0.24; p < 0.05) through Aβ1‐42 was observed.ConclusionExpression of cerebrovascular pathology fully mediates the effects of vascular risk factors on amyloid and accelerates manifestation of downstream biomarkers in the preclinical phases of AD, stressing the importance of vascular‐protective treatments.

P161 THE ROLE OF CARDIOLOGICAL TELEVISIT FOR THE MANAGEMENT OF PATIENTS WITH POST–ACUTE SEQUELAE OF SARS–COV–2 INFECTION: STUDY DESIGN

Abstract Background WHO defines Post–Acute Sequelae of SARS–CoV–2 (PASC) as a condition that occurs several weeks after the infection, which persists for at least 8 weeks and cannot be explained by alternative diagnoses. Symptoms of PASC are: palpitations, dyspnoea, chest pain. These symptoms require an initial cardiological investigation, but also a cardiological follow–up that could be carried out with telemedicine. Principal aim: To assess the feasibility of cardiological televisit and its socio–economic impact in patients with PASC. Secondary aims: 1) To describe the clinical, laboratory and instrumental characteristics of patients with PASC and to define the possible role of cardiovascular risk factors in the development of the disease; 2) To correlate the symptoms reported by the patients with any clinical objectivity or instrumental alterations; 3) To assess the patient‘s perception of the use of specialist televisit and its possible economic and social impact. Methods Prospective observational study. All patients with previous COVID–19 with suspected PASC will be screened. After the first cardiological face–to–face visit, patients with suspected PASC who require follow–up will be consecutively enrolled and assigned in a 1:1 ratio to the televised study group (GT) and the standard of care (GC) control group. Patients in the GT group will perform the control cardiology examination in televisit, while patients in the GC group will perform the cardiological control according to the current standard of care. The specialist televisit (booking mode, use of freeware platform) will be provided as indicated by the latest regional directives. Exclusion criteria: Failure to sign informed consent; inadequate computer literacy (of the patient or his/her caregiver). Evaluation: Patients in the GT and GC group will take a questionnaire with specific questions on how the specialist check–up will be delivered. Expected results: The use of televisit for the follow–up of patients with PASC, as defined in this protocol, play a key role for the digital transition in our operational context and, above all, for the optimisation of healthcare resources.

Cardiovascular Risk Factors in Patients With Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

The interruption of vascular supply to the inner ear is one of several proposed etiologies of sudden sensorineural hearing loss (SSNHL). The increased presence of cardiovascular risk factors may predispose patients to SSNHL through this pathway. This systematic review and meta-analysis studies the presence of cardiovascular risk factors in patients diagnosed with SSNHL. Databases included PubMed/Medline, OVID, EMBASE, Cochrane, and Web of Science. Inclusion criteria included studies featuring SSNHL patients presenting with 1+ cardiovascular risk factors. Exclusion criteria included case reports and studies without outcome measures. Two investigators independently reviewed all manuscripts and performed quality assessments using validated tools. Of 532 identified abstracts, 27 studies met inclusion criteria (19 case-control, 4 cohorts, 4 case series). Of these, 24 underwent meta-analysis encompassing a total of 77,566 patients (22,620 SSNHL patients, 54,946 matched controls). The mean age was 50.43 years. SSNHL patients were more likely to have concomitant diabetes (odds ratio [OR]1.61 [95% confidence interval [CI]: 1.31, 1.99; p < .00001]) and hypertension (OR 1.5[95% CI: 1.16, 1.94; p = .002]). An increased standard mean difference of total cholesterol of 11.09 mg/dL (95% CI; 3.51, 18.67; p = .004) was noted in the SSNHL group compared with the controls. No significant differences in smoking, high-density lipoprotein, triglycerides, or body mass indexwere detected. Patients presenting with SSNHL have a significantly higher risk of concomitant diabetes, hypertension, and higher total cholesterol in comparison to matched controls. This may indicate a higher cardiovascular risk profile in this population. More prospective and matched cohort studies are needed to understand the role of cardiovascular risk factors in SSNHL.

Subclinical atherosclerosis as detected by carotid ultrasound and associations with cardiac and HIV-specific risk factors; the Archi-Prevaleat project.

To evaluate the prevalence of carotid intima-media thickness (IMT) and plaques in a cohort of people living with HIV (PLWH), the role of cardiovascular risk factors, the impact of the antiretroviral regimens and the difference between naïve and experienced patients in the onset of carotid lesions. This project was initiated in 2019 and involves eight Italian centres. Carotid changes were detected using a power colour-Doppler ultrasonography with 7.5 MHz probes. The following parameters were evaluated: IMT of both the right and left common and internal carotids, data regarding risk factors for cardiovascular disease, HIV viral load, CD4 cell counts, serum lipids, glycaemia and body mass index. The associations between pathological findings and potential risk factors were evaluated by logistical regression, with odds ratios (ORs) and 95% confidence intervals (95% CI)s. Among 1147 evaluated PLWH, with a mean age of 52 years, 347 (30.2%) had pathological findings (15.8% plaques and 14.5% IMT). Besides the usual risk factors, such as older age, male sex and dyslipidaemia, CD4 cell nadir < 200 cells/mL (adjusted OR=1.51, 95% CI: 1.14-1.99) and current use of raltegravir (adjusted OR=1.54, 95% CI: 1.01-2.36) were associated with higher prevalence of pathological findings. Our data show that the current overall percentage of carotid impairments remains high. Colour-Doppler ultrasonography could play a pivotal role in identifying and quantifying atherosclerotic lesions among PLWH, even at a very premature stage, and should be included in the algorithms of comorbidity management of these patients.

Cardiovascular Risk Factors and Sudden Sensorineural Hearing Loss: A Case-Control Study.

To investigate the role of cardiovascular risk factors (specifically hypertension [HTN], hyperlipidemia/dyslipidemia, diabetes mellitus I and II, and body mass index (BMI) on the development of sudden sensorineural hearing loss (SSNHL). Case-control retrospective chart review. A tertiary referral center. Patients aged 18 to 85 years who presented to the clinic over a 1-year span (September 17, 2020 to September 17, 2021) for evaluation of sudden sensorineural hearing loss. Comparing the prevalence of the different cardiovascular risk factors (CVRFs) in patients with sudden sensorineural hearing loss compared with when compared with non-SSNHL patients at a neurotology clinic. Two hundred twenty-three patients with SSNHL were compared with age- and gender-matched comparison group to investigate the prevalence of cardiovascular risk factors within each group. There are no statistically significant differences (p > 0.05) in the prevalence of HTN, hyperlipidemia/dyslipidemia, diabetes mellitus I and II, and BMI in patients with sudden sensorineural hearing loss when compared with non-SSNHL patients at a neurotology clinic. Despite correlation between CVRF and SSNHL found in some other studies, we did not find a significant correlation between CVRF (diabetes, HTN, dyslipidemia, and high BMI) and SSNHL in our retrospective case control study of patients presenting to a nonacademic tertiary neurotology clinic. Although there may be other factors contributing to the pathogenesis of SSNHL, we have not yet identified these factors.

White matter integrity as a mediator between socioeconomic status and executive function.

Lower socioeconomic status (SES) is associated with poorer executive function, but the neural mechanisms of this association remain unclear. As healthy brain communication is essential to our cognitive abilities, white matter integrity may be key to understanding socioeconomic disparities. Participants were 201 African American and White adults (ages 33-72) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Diffusion tensor imaging was used to estimate regional fractional anisotropy as a measure of white matter integrity. Adjusting for age, analyses examined if integrity of the anterior limb of the internal capsule (ALIC), external capsule (EC), superior longitudinal fasciculus (SLF), and cingulum mediated SES-executive function relations. Lower SES was related to poorer cognitive performance and white matter integrity. Lower Trails B performance was related to poorer integrity of the ALIC, EC, and SLF, and lower Stroop performance was associated with poorer integrity of the ALIC and EC. ALIC mediated the SES-Trails B relation, and EC mediated the SES-Trails B and SES-Stroop relations. Sensitivity analyses revealed that (1) adjustment for race rendered the EC mediations non-significant, (2) when using poverty status and continuous education as predictors, results were largely the same, (3) at least some of the study's findings may generalize to processing speed, (4) mediations are not age-dependent in our sample, and (5) more research is needed to understand the role of cardiovascular risk factors in these models. Findings demonstrate that poorer white matter integrity helps explain SES disparities in executive function and highlight the need for further clarification of the biopsychosocial mechanisms of the SES-cognition association.

COVID-19, Endothelium and the Cardiometabolic Patient: A Possible Role for Capillary Leak Syndrome.

Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death. Sepsis leading to hemophagocytic lymphohistiocytosis (HLH) is a major risk factor; however, capillary hyper-permeability is the core underlying pathophysiological mechanism. Endothelial dysfunction plays a major role in cardiometabolic disease through insulin resistance, lipotoxicity, and, eventually, oxidative stress and chronic inflammation. We review the literature concerning the aforementioned mechanisms as well-established risk factors for adverse COVID-19 outcomes. We especially focus on data regarding the underlying endothelial effects of SARS-CoV-2 infection, including direct damage and increased vascular leakage through a hyper-inflammatory cascade and diminished nitric oxide bioavailability. Interestingly, an increased incidence of hypoalbuminemia has been observed in patients with severe COVID-19, especially those with underlying cardiometabolic disease. Importantly, low albumin levels present a strong, positive association with poor disease outcomes. Therefore, in this review article, we highlight the important role of cardiovascular risk factors on endothelium integrity and the possible link of endothelial damage in the hypoalbuminemia-associated adverse prognosis of COVID-19 patients.

Pathophysiology of Coronary Microvascular Dysfunction.

Ischemic heart disease (IHD) is commonly recognized as the consequence of coronary atherosclerosis and obstructive coronary artery disease (CAD). However, a significant number of patients may present angina or myocardial infarction even in the absence of any significant coronary artery stenosis and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenic mechanisms resulting in functional and/or structural changes in the coronary microcirculation and determining angina and myocardial ischemia in patients with angina without obstructive CAD ("primary" microvascular angina), as well as in several other conditions, including obstructive CAD, cardiomyopathies, Takotsubo syndrome and heart failure, especially the phenotype with preserved ejection fraction. The pathogenesis of CMD is complex and involves the combination of functional and structural alterations leading to impaired coronary blood flow and resulting in myocardial ischemia. In the absence of therapies specifically targeting CMD, attention has been focused on the role of modifiable risk factors. Here, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD, with a particular focus on the role of cardiovascular risk factors and comorbidities. Moreover, we discuss the specific pathogenic mechanisms of CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.

Role of Cardiovascular Risk Factors on the Association Between Physical Activity and Brain Integrity Markers in Older Adults.

Background and ObjectivesPhysical activity has been associated with a decreased risk for dementia, but the mechanisms underlying this association remain to be determined. Our objective was to assess whether cardiovascular risk factors mediate the association between physical activity and brain integrity markers in older adults.MethodsAt baseline, participants from the Age-Well study completed a physical activity questionnaire and underwent cardiovascular risk factors collection (systolic blood pressure, body mass index [BMI], current smoker status, and high-density lipoprotein cholesterol, total cholesterol, and insulin levels) and multimodal neuroimaging (structural MRI, diffusion MRI, FDG-PET, and florbetapir PET). Multiple regressions were conducted to assess the association among physical activity, cardiovascular risk factors, and neuroimaging. Mediation analyses were performed to test whether cardiovascular risk factors mediated the associations between physical activity and neuroimaging.ResultsA total of 134 cognitively unimpaired older adults (≥65 years) were included. Higher physical activity was associated with higher gray matter (GM) volume (β = 0.174, p = 0.030) and cerebral glucose metabolism (β = 0.247, p = 0.019) but not with amyloid deposition or white matter integrity. Higher physical activity was associated with lower insulin level and BMI but not with the other cardiovascular risk factors. Lower insulin level and BMI were related to higher GM volume but not to cerebral glucose metabolism. When controlling for insulin level and BMI, the association between physical activity and cerebral glucose metabolism remained unchanged, while the association with GM volume was lost. When insulin level and BMI were entered in the same model, only BMI remained a significant predictor of GM volume. Mediation analyses confirmed that insulin level and BMI mediated the association between physical activity and GM volume. Analyses were replicated within Alzheimer disease–sensitive regions and results remained overall similar.DiscussionThe association between physical activity and GM volume is mediated by changes in insulin level and BMI. In contrast, the association with cerebral glucose metabolism seems to be independent from cardiovascular risk factors. Older adults engaging in physical activity experience cardiovascular benefits through the maintenance of a lower BMI and insulin level, resulting in greater structural brain integrity. This study has implications for understanding how physical activity affects brain health and may help in developing strategies to prevent or delay age-related decline.Trial Registration InformationEudraCT: 2016-002,441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.

Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study.

Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45-2.49]; P=3.23×10-6) and reduced birthweight (OR=0.83 [95% CI=0.79-0.86]; P=3.96×10-18), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44-1.94]; P=7.45×10-12; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04-1.19]; P=1.19×10-3), but not with reduced birthweight. Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

The role of cardiovascular risk factors in maternal cardiovascular disease according to offspring birth characteristics in the HUNT study

A history of preterm or small (SGA) or large (LGA) for gestational age offspring is associated with smoking and unfavorable levels of BMI, blood pressure, glucose and lipids. Whether and to what extent the excess cardiovascular risk observed in women with these pregnancy complications is explained by conventional cardiovascular risk factors (CVRFs) is not known. We examined the association between a history of SGA, LGA or preterm birth and cardiovascular disease among 23,284 parous women and quantified the contribution of individual CVRFs to the excess cardiovascular risk using an inverse odds weighting approach. The hazard ratios (HR) between SGA and LGA offspring and CVD were 1.30 (95% confidence interval (CI) 1.15, 1.48) and 0.89 (95% CI 0.76, 1.03), respectively. Smoking explained 49% and blood pressure may have explained ≈12% of the excess cardiovascular risk in women with SGA offspring. Women with preterm birth had a 24% increased risk of CVD (HR 1.24, 95% CI 1.06, 1.45), but we found no evidence for CVRFs explaining any of this excess cardiovascular risk. While smoking explains a substantial proportion of excess cardiovascular risk in women with SGA offspring and blood pressure may explain a small proportion in these women, we found no evidence that conventional CVRFs explain any of the excess cardiovascular risk in women with preterm birth.

Impact of Cardiovascular Risk Factors on the Occurrence of Cardiovascular Events in Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitides.

Despite improvement in the prognosis of ANCA-associated vasculitides (AAVs), increased mortality, mainly from a cardiovascular origin, persists. We aimed to determine the role of cardiovascular risk factors (CVRFs) on the occurrence of major cardiovascular events (MACEs) in AAVs. Patients with AAVs were successively included in a prospective cohort study, which assessed CVRFs (defined by age >50 years in men and >60 years in women, personal history of cardiovascular disease, smoking status, obesity, diabetes, dyslipidemia, hypertension, and sedentary lifestyle), the use of glucocorticoids and immunosuppressive agents at baseline and during follow-up, and the occurrence of MACEs. One hundred and three patients were included, with a median follow-up time of 3.5 years. In the glucocorticoids and cyclophosphamide adjusted multivariate analysis, the occurrence of MACEs was associated with older age (p = 0.001, OR = 14.71, 95% CI (confidence interval) = 2.98–72.68), cardiovascular history (p = 0.007, OR (odds ratio) = 6.54, 95% CI = 1.66–25.71), sedentary lifestyle (p = 0.011, OR = 4.50, 95% CI = 1.42–14.29), hypertension (p = 0.017, OR = 5.04, 95% CI = 1.33–19.12), and dyslipidemia (p = 0.03, OR = 3.86, 95% CI = 1.14–13.09). The occurrence of MACEs was associated with the number of CVRFs (p < 0.001), but not with the use of glucocorticoids or cyclophosphamide (p = 0.733 and p = 0.339, respectively). The implementation of a screening and management program for modifiable CVRFs, particularly hypertension, sedentary lifestyle, and dyslipidemia, may be beneficial for AAV patients in order to reduce their cardiovascular risk.

PREMATURE AGING INDICES IN PATIENTS WITH MODERATE CARDIOVASCULAR RISK

Aging is characterized with a gradual aggravation of organ function throughout life and can occur both physiologically and prematurely. With premature aging there is an early decrease in the adaptive mechanisms of all physiological systems of the body, there is a significant reduction in physical and mental activities, that contributes to the early development of age−related pathology. Genetic and epigenetic factors, as well as environmental ones can be the causes of different rates of aging. It is not possible to accurately determine the onset of old age by biological characteristics, because people with the same calendar age are not always the same as for biological one. To establish the association of age−related disease factors with the markers of premature aging and biological age in the patients of various age groups, a study was performed in the patients aged 25−44 and 45−59 years with moderate cardiovascular risk in accordance with the SCORE scale. The primary task for predicting and preventing the age−associated diseases is to identify genetic, molecular and cellular factors that determine the rate of aging and increase the risk of age−associated diseases. The role of cardiovascular risk factors in premature aging has been determined. It is established that the most important factors that lead to an increase in biological age and formation of age−associated diseases are the disorders of lipid and carbohydrate metabolism and level of oxidative stress, importance of which progresses with age. The relationship between cardiovascular risk factors and biological age, estimated with different methods, their influence on telomere length, that allows the designing of an algorithm to determine the markers of premature aging in different age groups for early and effective prevention of metabolic−associated diseases, has been established. Key words: biological age, cardiovascular risk, premature aging, telomere length.