The optimal WC cut-off points for the prediction of subclinical CVD as measured by carotid intima-media thickness among African adults: a cross-sectional study

Background Increased waist circumference (WC) is one of the cardiovascular disease (CVD) risk factors used to predict cardiovascular events. Waist circumference cut-off values for predicting metabolic syndrome and other cardiovascular risks have been previously studied. Carotid intima-media thickness (CIMT) is one of the cardiovascular risk factor recently described and reported to be suitable as it is a direct measurement of vascular quality. Hence the aim of the present study was to determine the optimal WC cut-off point for the prediction of subclinical CVD. Methods The study was a cross-sectional study using quantitative methods, conducted among 1318 adults aged between 40 and 60 years old, residing in a rural Black population in Limpopo province. Carotid Intima-Media Thickness measurements were performed using a LOGIQ ultrasound system (GE Healthcare, CT, USA). Waist Circumference (WC) (cm) was measured to the nearest 0.1 cm. Bivariate correlation, logistic regression and receiver operating characteristic were analysed using the statistical package for social sciences version 26.0 software. Results Among the total population, 69% were women and 31% men with a mean age of 53 ± 7 years. Among women, WC at a cut-off value of 95 cm gave the highest sensitivity of 57%, the specificity of 55% and an area under the curve (AUC) of 0.588. In men, an optimum WC cut-off point of 82 cm yielded the highest sensitivity and specificity at 72% and 70% respectively, with an AUC of 0.767 p < 0.001. Conclusion The traditional waist circumference cut-off points (94 cm for women and 80 cm for men) that are currently used for the diagnosis of metabolic syndrome might not be suitable in the prediction of an increased CIMT.

Central Blood Pressure and Subclinical Atherosclerotic Risk in Young Hispanic American Women

Background: The incidence of younger women being hospitalized from cardiovas­cular disease (CVD) events is on the rise. Hispanic women are generally thought to have higher CVD risk factor burden than non-Hispanic White (NHW) women yet Hispanic Americans have lower mortality from CVD. Traditional measures of CVD may not accurately capture CVD risk in His­panic Americans. Hence, the purpose of this study was to assess the impact of ethnicity on vascular reactivity and central hemody­namic load to gain insight into subclinical CVD risk in young women.Methods: Brachial flow-mediated dilation (FMD), low-flow mediated constriction (L-FMC), carotid-femoral pulse wave velocity (cfPWV), and pulse wave analysis (from synthesized aortic pressure waveforms) were measured in 25 Hispanic women and 31 NHW women aged between 18-35 years. FMD and L-FMC were combined to provide an index of total vessel reactivity.Results: NHW and Hispanic women did not differ in age or traditional CVD risk factors (P>.05 for all). Compared with NHW women, Hispanic women had greater vascular reactivity (8.7±4.1 vs 11.7±4.1 %, P=.011), lower central pulse pressure (28±5 vs 24±3 mm Hg, P=.001) and lower pressure from wave reflections (12±2 vs 10±1 mm Hg, P=.001). There were no differences in cfPWV between NHW women and Hispanic women (5.4±0.7 vs 5.3±0.7 m/s, P=.73).Conclusion: Young Hispanic women have greater vascular reactivity and lower central pulsatile hemodynamic load compared with NHW women, suggesting lower subclinical CVD risk.Ethn Dis. 2021;31(4):489-500; doi:10.18865/ed.31.4.489

Neutrophil Pathways of Inflammation Characterize the Blood Transcriptomic Signature of Patients with Psoriasis and Cardiovascular Disease

Background: Patients with psoriasis have an increased risk of atherosclerotic cardiovascular disease (CVD). The molecular mechanisms behind this connection are not fully understood, but the involvement of neutrophils have drawn attention as a shared inflammatory factor. Methods: RNA sequencing using the Illumina platform was performed on blood from 38 patients with moderate to severe psoriasis; approximately half had prior CVD. The neutrophil to lymphocyte ratio (NLR) was obtained from blood samples. Subclinical atherosclerosis was assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and ultrasound imaging. Transcriptomic analysis for differential expression and functional enrichment were performed, followed by correlation analyses of differentially expressed genes (DEGs), NLR and subclinical measurers of CVD. Results: 291 genes were differentially expressed between patients with psoriasis with and without CVD. These included 208 upregulated and 83 downregulated DEGs. Neutrophil degranulation was identified as the most significant process related to the upregulated DEGs. Genes for the neutrophil-associated markers MPO, MMP9, LCN2, CEACAM1, CEACAM6 and CEACAM8 were identified as being of special interest and their mRNA levels correlated with NLR, high-sensitive C-reactive protein and markers of subclinical CVD. Conclusions: Patients with psoriasis and CVD had an increased expression of genes related to neutrophil degranulation in their blood transcriptome compared with patients with psoriasis without CVD. NLR may be a potential biomarker of subclinical CVD in psoriasis.

Gut Microbiota and Subclinical Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus

Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD). The gut microbiota may contribute to the onset and progression of T2D and CVD. The aim of this study was to evaluate the relationship between the gut microbiota and subclinical CVD in T2D patients. This cross-sectional study used echocardiographic data to evaluate the cardiac structure and function in T2D patients. We used a quantitative polymerase chain reaction to measure the abundances of targeted fecal bacterial species that have been associated with T2D, including Bacteroidetes, Firmicutes, Clostridium leptum group, Faecalibacterium prausnitzii, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. A total of 155 subjects were enrolled (mean age 62.9 ± 10.1 years; 57.4% male and 42.6% female). Phyla Bacteroidetes and Firmicutes and genera Bacteroides were positively correlated with the left ventricular ejection fraction. Low levels of phylum Firmicutes were associated with an increased risk of left ventricular hypertrophy. High levels of both phylum Bacteroidetes and genera Bacteroides were negatively associated with diastolic dysfunction. A high phylum Firmicutes/Bacteroidetes (F/B) ratio and low level of genera Bacteroides were correlated with an increased left atrial diameter. Phyla Firmicutes and Bacteroidetes, the F/B ratio, and the genera Bacteroides were associated with variations in the cardiac structure and systolic and diastolic dysfunction in T2D patients. These findings suggest that changes in the gut microbiome may be the potential marker of the development of subclinical CVD in T2D patients.

Upregulated anti-angiogenic miR-424-5p in type 1 diabetes (model of subclinical cardiovascular disease) correlates with endothelial progenitor cells, CXCR1/2 and other parameters of vascular health

Background In spite of clinical progress, cardiovascular disease (CVD) remains the predominant cause of mortality worldwide. Overexpression studies in animals have proven miR-424-5p to have anti-angiogenic properties. As type 1 diabetes mellitus (T1DM) without CVD displays endothelial dysfunction and reduced circulating endothelial progenitor cells (cEPCs), it offers a model of subclinical CVD. Therefore, we explored miR-424-5p, cytokines and vascular health in T1DM. Methods Twenty-nine well-controlled T1DM patients with no CVD and 20-matched controls were studied. Cytokines IL8, TNF-α, IL7, VEGF-C, cEPCs/CD45dimCD34+CD133+ cells and ex-vivo proangiogenic cells (PACs)/fibronectin adhesion assay (FAA) were measured. MiR-424-5p in plasma and peripheral blood mononuclear cells (PBMC) along with mRNAs in PBMC was evaluated. Results We found an elevation of IL7 (p = 0.008), IL8 (p = 0.003), TNF-α (p = 0.041), VEGF-C (p = 0.013), upregulation of mRNA CXCR1 (p = 0.009), CXCR2 (p < 0.001) and reduction of cEPCs (p < 0.001), PACs (p < 0.001) and FAA (p = 0.017) in T1DM. MiR-424-5p was upregulated in T1DM in PBMC (p < 0.001). MiR-424-5p was negatively correlated with cEPCs (p = 0.006), PACs (p = 0.005) and FAA (p < 0.001) and positively with HbA1c (p < 0.001), IL7 (p = 0.008), IL8 (p = 0.017), VEGF-C (p = 0.007), CXCR1 (p = 0.02) and CXCR2 (p = 0.001). ROC curve analyses showed (1) miR-424-5p to be a biomarker for T1DM (p < 0.001) and (2) significant upregulation of miR-424-5p, defining subclinical CVD, occurred at HbA1c of 46.5 mmol/mol (p = 0.002). Conclusion We validated animal research on anti-angiogenic properties of miR-424-5p in T1DM. MiR-424-5p may be a biomarker for onset of subclinical CVD at HbA1c of 46.5 mmol/mol (pre-diabetes). Thus, miR-424-5p has potential use for CVD monitoring whilst anti-miR-424-5p-based therapies may be used to reduce CVD morbidity/mortality in T1DM.

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in a Community-Based Cohort: Data From the Washington, D.C. Cardiovascular Health and Needs Assessment

Background: Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar 18Fluorodeoxyglucose (18FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort.Methods: Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including 18FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity.Results: AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, p = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, p = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (β = 0.41, p = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity.Conclusions: AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.

Imaging modalities for cardiovascular phenotyping in asymptomatic people living with HIV

Cardiovascular disease (CVD) has emerged as a leading cause of non-HIV-related mortality among people living with HIV (PLWH). Despite the growing CVD burden in PLWH, there is concern that general population risk score models may underestimate CVD risk in these patients. Imaging modalities have received mounting attention lately to better understand the pathophysiology of subclinical CVD and provide improved risk assessment in this population. To date, traditional and well-established techniques such as echocardiography, pulse wave velocity, and carotid intima thickness continue to be the basis for the diagnosis and subsequent monitoring of vascular atherosclerosis and heart failure. Furthermore, novel imaging tools such as cardiac computed tomography (CT) and cardiac CT angiography (CCTA), positron emission tomography/CT (PET/CT), and cardiac magnetic resonance (CMR) have provided new insights into accelerated cardiovascular abnormalities in PLWH and are currently evaluated with regards to their potential to improve risk stratification.

Abstract 16407: Plasma Omega-3 Fatty Acids Predict Cardiovascular Events Stratified by Coronary Artery Calcium

Background: In REDUCE-IT, high-dose eicosapentaenoic acid (EPA) was beneficial in high-risk patients without clinical CVD independent of triglyceride levels. Whether the benefit of higher plasma EPA extends to those without subclinical CVD is unclear. Hypothesis: In those without clinical CVD, plasma omega-3 fatty acid (O3FA) levels predict long-term CVD events, and subclinical CVD measured by coronary artery calcium (CAC) modifies the effect such that individuals with the highest CAC attain the greatest benefit from higher O3FA. Methods: We examined 6568 MESA participants with plasma EPA and docosahexaenoic acid (DHA) levels measured at baseline and classified them by tertiles of EPA and DHA and by CAC category (0, 1-99, ≥100). Our outcome was time to CVD event (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Cox regression models were used to assess the associations between log-transformed EPA and DHA and CVD events adjusted for demographic factors, CVD risk factors, and medication use. Results: Mean age was 62.1±10.2 and 52.9% were females. Higher log(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.93; P = 0.002) and log(DHA) (aHR = 0.80; 95% CI, 0.66-0.96; P = 0.019) were independently associated with fewer CVD events. The difference in absolute CVD event rates between the lowest and highest EPA tertile increased at higher CAC levels (Figure). The adjusted HR for highest compared to lowest EPA tertile within CAC 0 was 1.02 (95% CI, 0.72-1.45), CAC 1-99 was 0.71 (95% CI, 0.51-0.98), and CAC≥100 was 0.66 (95% CI, 0.52-0.83). A similar association was seen in tertiles of DHA by CAC category. These findings were consistent by sex and race category and after adjusting for O3FA supplement use. Conclusion: In an ethnically diverse population free of clinical CVD at baseline, higher plasma O3FA levels were associated with fewer CVD events. The absolute reduction in CVD events with higher O3FA levels was more apparent at higher CAC scores.

Abstract 14784: Sleep Moderates the Association Between Arterial Stiffness and Blood Pressure Variability

Introduction: Both arterial stiffness and short-term blood pressure variability (BPV) are important subclinical biomarkers of cardiovascular disease (CVD). Evidence is accumulating that poor sleep is associated with subclinical CVD. The purpose of our study was to investigate how sleep was related to arterial stiffness and BPV. We also explored if sleep changed the association between arterial stiffness and BPV. Methods: In this cross-sectional study, objective sleep characteristics were assessed by a wrist actigraphy over two days. Arterial stiffness was measured by carotid femoral pulse wave velocity (cfPWV). BPV was evaluated using an ambulatory blood pressure monitor over 24 hours and estimated by average real variability. Results: The sample included 87 healthy adults aged between 35 and 64 years. Sleep efficiency was an independent predictor of cfPWV and systolic BPV (SBPV), while wake after sleep onset (WASO) was an independent predictor of cfPWV, only. In addition, cfPWV showed a positive relationship with SBPV, and this relationship was moderated by sleep efficiency and WASO, respectively. The relationship between cfPWV and SBPV became stronger among individuals who had a level of sleep efficiency lower than 84% and who had WASO higher than 67 minutes, respectively. Conclusions: Our study showed that poor sleep not only had a direct link with arterial stiffness and BPV, but also moderated the relationship between these two subclinical CVD biomarkers. These findings implied that improving sleep quality could be a target intervention to promote cardiovascular health in clinical practice.

The Role of miR-342 in Vascular Health. Study in Subclinical Cardiovascular Disease in Mononuclear Cells, Plasma, Inflammatory Cytokines and PANX2

Cardiovascular disease (CVD) correlates with inflammation and a reduction in circulating endothelial progenitor cells (cEPCs). Recently, CVD was shown to be the main cause of mortality in individuals with type 1 diabetes (T1DM). In animals, miR-342 was shown to exert an anti-inflammatory effect in CVD. Hypothesis: miR-342-3p/-5p are downregulated in subclinical CVD (T1DM), whereas inflammatory cytokines are upregulated. We studied miR -342 -3p/5p in plasma/peripheral blood mononuclear cells (PBMCs) in 29 T1DM and 20 controls (HC). Vascular health was measured by fibronectin adhesion assay (FAA), cEPCs (CD45dimCD34+133+ cells) and by assessing inflammation and tissue inhibition of metalloproteases (TIMP-1). In T1DM IL-7, IL-8, TNFα and VEGF-C were increased in plasma. MiR-342-3p/-5p were downregulated in PBMCs in T1DM, but not in plasma. PANX2, chemokine receptors CXCR1/2 mRNAs, were increased in PBMCs in T1DM. MiR-342-3p was negatively correlated with TIMP-1, IL-6, IL-8, TNF-α, HbA1c and CXCR2, whilst miR-342-5p was negatively correlated with TIMP-1, IL-6, IL-8 and HbA1c. There was a positive correlation among miR-342-3p, FAA and cEPCs, and between miR-342-5p and cEPCs. ROC curve analyses showed significant downregulation of miR-342-3p/-5p at HbA1c > 46.45 mmol/mol, indicating their potential as biomarkers for subclinical CVD. Our findings validated animal studies and confirmed the proangiogenic properties of miR-342-3p/-5p. MiR-342-3p/-5p-based intervention or monitoring may prove to be beneficial in managing CVD.