scholarly journals Biomarkers representing key aging-related biological pathways are associated with subclinical atherosclerosis and all-cause mortality: The Framingham Study

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251308
Author(s):  
Cecilia Castro-Diehl ◽  
Rachel Ehrbar ◽  
Vanesa Obas ◽  
Albin Oh ◽  
Ramachandran S. Vasan ◽  
...  

Background Increased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality. Methods and results We evaluated up to 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium [ln (CAC+1)] and carotid intima-media thickness (IMT). In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values (βADMA per 1-SD increase 0.25; 95% confidence interval [CI] [0.11, 0.39]). Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values (βLTL −0.08, 95%CI −0.14, −0.02, and βIGF-1 −0.04, 95%CI −0.08, −0.01, respectively). During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality (hazard ratios [HR] per SD increase in biomarker, 0.85, 95% CI 0.74–0.99, and 0.90, 95% CI 0.82–0.98 for LTL and IGF-1, respectively). F2-Isoprostanes and ADMA values were positively associated with all-cause mortality (HR per SD increase in biomarker, 1.15, 95% CI, 1.10–1.22, and 1.10, 95% CI, 1.02–1.20, respectively). Conclusion In our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults.

2021 ◽  
Vol 11 (13) ◽  
pp. 6091
Author(s):  
Pietro Scicchitano ◽  
Marco Tucci ◽  
Gabriella Ricci ◽  
Michele Gesualdo ◽  
Santa Carbonara ◽  
...  

Background: The aim of this study was to assess the role of cardiac and vascular parameters as all-cause mortality determinants in patients suffering from gynecological cancers. Methods: This was an observational, prospective, non-randomized, and non-controlled study. Forty-seven consecutive patients (mean age: 58 ± 13 years) were enrolled after cancer staging. All patients underwent evaluation of vascular (common carotid intima-media thickness (mean C-IMT), flow-mediated dilation of the brachial artery (FMD), and antero-posterior diameter of the infrarenal abdominal aorta (APAO)) and cardiac function and morphology before cancer-related interventions. A 6-year follow-up was carried out to assess the overall survival of the whole population. Results: Twenty patients (42%) died by the time of the 6-year follow-up. The brachial artery FMD values were higher in the survivors than the non-survivors (9.71 ± 3.53% vs. 6.13 ± 2.62%, p < 0.001), as well as the LVEF (60.8 ± 3.0% vs. 57.8 ± 4.4%, p = 0.009). There were no differences in the mean C-IMT, APAO, and other echocardiographic parameters. ROC curve analysis identified a baseline LVEF < 57% and FMD value < 5.8% as the best cut-offs. Kaplan–Meier evaluation showed that the LVEF, tricuspid annular plane systolic excursion, and FMD were the best predictors of all-cause mortality, although only the LVEF and FMD were confirmed in multivariate Cox regression analysis. Conclusions: The LVEF and brachial artery FMD are independent prognostic determinants in patients with gynecological cancers.


Author(s):  
Annalise E Zemlin ◽  
Tandi E Matsha ◽  
Andre P Kengne ◽  
Gloudina M Hon ◽  
Rajiv T Erasmus

Background E-selectin, an adhesion molecule, is a specific marker of endothelial dysfunction. High concentrations have been reported in type 2 diabetes and disorders with high risk of cardiovascular disease (CVD). Measurement of carotid intima-media thickness (CIMT) is a surrogate marker of early atherosclerosis. We examined the relationship between E-selectin concentrations, CIMT and cardio-metabolic traits in normo- and hyperglycaemic mixed ancestry South Africans. Methods E-selectin concentrations were determined in 308 subjects from the Cape Town Bellville South Community–based study on a mixed ancestry population. Their correlation with CIMT and cardio-metabolic profile used robust correlations and linear regression models. Results E-selectin concentrations were significantly higher in the hyperglycaemic (median 139.8 µg/L) compared to the normoglycaemic group (median 118.8 µg/L), ( p = 0.0007). Significant differences between the two groups were found for markers of glycaemia and adiposity, but not for CIMT. Significant correlations were found between E-selectin and age, markers of glycaemia and inflammation, central obesity and lipid variables. Associations remained significant only with age, hyperglycaemia and C-reactive protein in robust linear regression models. In similar regressions models, age and gender were the main predictors of CIMT, which was not associated with E-selectin. Conclusions E-selectin concentrations in this study were associated with hyperglycaemia, possibly reflecting early endothelial damage. However, E-selectin was not useful to assess CIMT, a marker of subclinical atherosclerosis, which appeared to be determined by ageing and male gender.


Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Menglu Liang ◽  
John William (Bill) McEvoy ◽  
Yuan Chen ◽  
A. Richey Sharrett ◽  
Elizabeth Selvin

Introduction: Serum 1,5-anhydroglucitol (1,5-AG) concentrations decrease in the setting of acute hyperglycemia, making 1,5-AG a useful biomarker of glucose peaks. In recent studies, 1,5-AG has been associated with clinical cardiovascular disease events. However, the association between 1,5-AG and subclinical vascular disease is unknown. Hypothesis: 1,5-AG will be associated with subclinical myocardial damage (assessed by cardiac troponin T measured using a novel highly sensitive assay (hs-cTnT)) and subclinical atherosclerosis (assessed by ultrasound-detected carotid intima-media thickness (cIMT)), particularly in persons with diabetes. Methods: We measured 1,5-AG in 10,753 participants in the ARIC Study at visit 2 (1990[[Unable to Display Character: &#8211;]]1992) and conducted a cross-sectional analysis to characterize the associations of 1,5-AG with elevated hs-cTnT (≥ 14 ng/L) or thick cIMT (top quartile, ≥0.79 mm) using logistic regression models. We also evaluated the prospective association between baseline 1,5-AG and incident elevated hs-cTnT at 6-years using Poisson regression models. Results: Among diabetics, those with 1,5-AG <6 ug/mL were 5 times more likely to have prevalent elevated hs-TnT at baseline compared to non-diabetics with 1,5-AG >10 ug/mL (adjusted OR 4.67, 95%CI, 3.27[[Unable to Display Character: &#8211;]]6.68) and almost 2 times more likely to be in the top quartile of the cIMT (adjusted OR 1.75, 95%CI 1.39-2.19). 1,5-AG <6 ug/mL in persons with diabetes was also significantly associated with 6-year incident elevated hs-TnT: RR 2.26 (95%CI, 1.50[[Unable to Display Character: &#8211;]]3.39). The associations of 1,5-AG with elevated hs-TnT and thick cIMT were non-linear and mostly driven by persons with diabetes (Figure). Conclusions: 1,5-AG was associated with prevalent and incident subclinical cardiovascular disease in persons with diabetes in the community. Our results suggest that glucose peaks may be relevant for the development of subclinical cardiac damage and atherosclerosis in persons with diabetes.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Shin-ya Nagasawa ◽  
Katsuyuki Miura ◽  
Akira Fujiyoshi ◽  
Aya Kadota ◽  
Takayoshi Ohkubo ◽  
...  

Objective: Asymmetrical dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is known as a mediator of endothelial cell dysfunction. Some clinical studies have found evidence that increased plasma ADMA levels are associated with a higher risk of cerebrovascular events. However, studies on the relationship of plasma ADMA to subclinical atherosclerosis have been scarce. We evaluated the association of ADMA with carotid intima-media thickness (IMT) in population-based samples in Japan. Methods: Population-based Japanese samples composed of 313 men aged 40-49 (40s men) from the ERA-JUMP and 732 men aged 60-79 (60s+70s men) from the SESSA were examined with physical examinations, life-style questionnaires, laboratory assessment and IMT using standardized methods. Plasma samples were stored at -80°C, and concentration of ADMA was determined using a validated high-throughput liquid chromatographic-tandem mass spectrometric assay. The IMTs of the right and left common carotid arteries, the carotid bulbs, and the internal carotid arteries were examined. Statistical associations were evaluated using multiple linear regression models with adjustment for age, body mass index, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, fasting blood glucose, smoking, alcohol intake, medications for hypertension, hyperlipidemia, or diabetes, and estimated glomerular filtration rate (eGFR) . Results: The average concentrations and standard deviation (SD) of plasma ADMA in men aged 40-49 and 60-79 were 0.39 ± 0.06 and 0.43 ± 0.06 μmol/L, respectively. The mean and SD of IMT in men aged 40-49 and 60-79 were 0.61 ± 0.07 and 0.91 ± 0.20 mm, respectively. Higher level of ADMA was significantly and positively associated with proportion of current smoking both in 40s and 60s+70s men (correlation coefficient: both p <0.001). It was also significantly and positively associated with eGFR in 60s+70s men (p <0.001) but not associated with eGFR in 40s men (p = 0.429). In full adjusted linear regression models, 1 SD increase in ADMA was associated with 0.14mm increase in IMT in 40s men (p=0.01) but only 0.04mm increase in IMT in 60s+70s men (p=0.26). Conclusions: Higher level of ADMA was associated with more IMT independently of traditional risk factors and renal function in young adult men, but not in elderly men.


Author(s):  
Chuan-Wei Yang ◽  
Yuh-Cherng Guo ◽  
Chia-Ing Li ◽  
Chiu-Shong Liu ◽  
Chih-Hsueh Lin ◽  
...  

Carotid intima–media thickness (IMT), plaque, and stenosis are widely used as early surrogate markers of subclinical atherosclerosis and strong predictors of future deaths and cardiovascular events. Albuminuria is an indicator of generalized endothelial dysfunction that speeds up atherosclerosis. However, previous studies reporting these associations cannot rule out the confounding effect of albuminuria. We aimed to examine the independent and joint relationships between IMT markers and 10-year mortality in community-dwelling Taiwanese adults. This work was a community-based prospective cohort study consisting of 2956 adults aged at least 30 years recruited in 2007 and followed up through 2019. Cox proportional hazard regression models were used to examine associations of these subclinical atherosclerosis markers with mortality. During an average of 9.41 years of follow up, 242 deaths occurred. The mortality rate was 8.70 per 1000 person-years. Compared with those with carotid IMT less than 1.0 mm, persons with severely increased carotid IMT (≥2.0 mm) had an increased risk for death (hazard ratio (HR): 1.79; 95% confidence interval (CI): 1.07, 3.00). Compared with those without carotid plaque, persons with carotid plaque were more likely to have an increased risk for death (1.65; 1.21–2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25–36% had a significant increased risk for death (1.57; 1.12–2.22). Considering these three IMT markers along with the traditional risk factors (c-statistic: 0.85) significantly increased their predictive ability of mortality compared with any individual variable’s predictive ability (all p-values < 0.001 for comparisons of c-statistic values). Carotid IMT measures, including IMT thickness, carotid plaque, and carotid stenosis were significant independent predictors of mortality. Our study supports evidence of blood pressure-related media thickening markers to assess future mortality risks in Chinese adults of general population.


2021 ◽  
Vol 10 (5) ◽  
pp. 955
Author(s):  
Ovidiu Mitu ◽  
Adrian Crisan ◽  
Simon Redwood ◽  
Ioan-Elian Cazacu-Davidescu ◽  
Ivona Mitu ◽  
...  

Background: The current cardiovascular disease (CVD) primary prevention guidelines prioritize risk stratification by using clinical risk scores. However, subclinical atherosclerosis may rest long term undetected. This study aimed to evaluate multiple subclinical atherosclerosis parameters in relation to several CV risk scores in asymptomatic individuals. Methods: A cross-sectional, single-center study included 120 asymptomatic CVD subjects. Four CVD risk scores were computed: SCORE, Framingham, QRISK, and PROCAM. Subclinical atherosclerosis has been determined by carotid intima-media thickness (cIMT), pulse wave velocity (PWV), aortic and brachial augmentation indexes (AIXAo, respectively AIXbr), aortic systolic blood pressure (SBPao), and ankle-brachial index (ABI). Results: The mean age was 52.01 ± 10.73 years. For cIMT—SCORE was more sensitive; for PWV—Framingham score was more sensitive; for AIXbr—QRISK and PROCAM were more sensitive while for AIXao—QRISK presented better results. As for SBPao—SCORE presented more sensitive results. However, ABI did not correlate with any CVD risk score. Conclusions: All four CV risk scores are associated with markers of subclinical atherosclerosis in asymptomatic population, except for ABI, with specific particularities for each CVD risk score. Moreover, we propose specific cut-off values of CV risk scores that may indicate the need for subclinical atherosclerosis assessment.


2020 ◽  
pp. 1-8
Author(s):  
Silvia M. Cardoso ◽  
Michele Honicky ◽  
Yara M. F. Moreno ◽  
Luiz R. A. de Lima ◽  
Matheus A. Pacheco ◽  
...  

Abstract Background: Subclinical atherosclerosis in childhood can be evaluated by carotid intima-media thickness, which is considered a surrogate marker for atherosclerotic disease in adulthood. The aims of this study were to evaluate carotid intima-media thickness and, to investigate associated factors. Methods: Cross-sectional study with children and adolescents with congenital heart disease (CHD). Socio-demographic and clinical characteristics were assessed. Subclinical atherosclerosis was evaluated by carotid intima-media thickness. Cardiovascular risk factors, such as physical activity, screen time, passive smoke, systolic and diastolic blood pressure, waist circumference, dietary intake, lipid parameters, glycaemia, and C-reactive protein, were also assessed. Factors associated with carotid intima-media thickness were analysed using multiple logistic regression. Results: The mean carotid intima-media thickness was 0.518 mm and 46.7% had subclinical atherosclerosis (carotid intima-media thickness ≥ 97th percentile). After adjusting for confounding factors, cyanotic CHD (odds ratio: 0.40; 95% confidence interval: 0.20; 0.78), cardiac surgery (odds ratio: 3.17; 95% confidence interval: 1.35; 7.48), and be hospitalised to treat infections (odds ratio: 1.92; 95% confidence interval: 1.04; 3.54) were associated with subclinical atherosclerosis. Conclusion: Clinical characteristics related to CHD were associated with subclinical atherosclerosis. This finding suggests that the presence of CHD itself is a risk factor for subclinical atherosclerosis. Therefore, the screen and control of modifiable cardiovascular risk factors should be made early and intensively to prevent atherosclerosis.


Author(s):  
Eliana Portilla-Fernández ◽  
Shih-Jen Hwang ◽  
Rory Wilson ◽  
Jane Maddock ◽  
W. David Hill ◽  
...  

AbstractCommon carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1428.2-1428
Author(s):  
V. Valinotti ◽  
A. Paats ◽  
R. Acosta ◽  
L. Roman ◽  
I. Acosta-Colman ◽  
...  

Background:The mechanism of increased cardiovascular risk in RA is not well understood and is independent of traditional CV risk factors. Intima-media thickness of the common carotid wall measured by ultrasonogram is a safe and useful biomarker of early stage atherosclerosis that correlates with coronary involvement; and it correlates with severity and duration of disease. Several studies have shown a relationship between inflammation markers, endothelial dysfunction markers, and carotid involvement. (1)Objectives:To determine the presence of inflammation biomarkers and its relationship with subclinical atherosclerosis measured by carotid ultrasound, and with the clinical characteristics in patients with established Rheumatoid Arthritis (RA)Methods:Descriptive, cross sectional, prospective study, in a Paraguayan cohort of patients with RA meeting ACR/EULAR2010 criteria. This study had two phases: the first one, included a standardized questionnaire according to the variables included in the Cardiovascular Risk project (PINV15-0346), from the National Sciences and Technology Council (CONACYT), and physical examination; the second one included laboratory sample collection performed by a specialized laboratory for serum biomarkers measurement for cardiovascular risk prediction (i.e endothelin, alpha-TNF, E-selectin, homocysteine, apolipoprotein, fibrinogen, and high sensitivity-CRP levels) and carotid ultrasound evaluation by a trained specialist, to evaluate subclinical atherosclerosis. Subclinical atherosclerosis was defined as carotid intima-media thickness (CIMT) >0,9mm and/or presence of carotid plaques. All patients signed informed consent. SPSS 23rd version was used for data analysis. Quantitative variables were presented as means and qualitative as frequencies. Chi square test was performed for comparisons between dichotomous variables and t Student for continuous, and p ≤ 0.05 for statistical significance.Results:100 patients were included, 87% were women, mean disease duration 130.9±102.64 months, 77% were RF positive, and 84.4% were ACPA positive, 43.4% had bone erosions, mean ESR-DAS28 was 3,42±1,1; 30% had remission criteria. 39% had extra-articular manifestations.Elevated serum biomarkers were found: fibrinogen >400 mg/dL 88.2%, high sensitivity-CRP (hs-CRP) >5mg/dL 42.9%, endothelin >2 ng/mL 20%, alpha-TNF >15,6 pg/mL 13.1%, E-selectin >79,2 ng/mL 6%. 25.3% had CIMT >0,9 mm and mean CIMT was 0.68±0.25mm. 27.14% had carotid plaques. Patients with CIMT>1mm had higher frequency of family history of arterial hypertension (p=0.006), greater mean disease duration (p=0.0007), hip circumference (p=0.014), blood pressure (SBP p=0.038, DBP p=0.027), HAQ levels (p=0,019) and hs-CRP levels (p=0.013), also lower mean height (p=0,04); while carotid plaques were related to higher homocysteine (p=0.026) and hs-CRP levels (p=0.024).Conclusion:A considerable percentage of patients had subclinical atherosclerosis. Patients with CIMT>0,9mm had a longer disease duration, higher HAQ levels, hip circumference, as well as higher BP. High levels of hs-CRP were more frequently related to the presence of subclinical atherosclerosisReferences:[1]Aday, A. targeting residual inflammatory risk: a shifting paradigm for atherosclerotic disease. Frontiers in cardiovascular medicine. 2019. 6:16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403155/pdf/fcvm-06-00016.pdfDisclosure of Interests:None declared


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