Vascular Biomarkers and Surrogates in Cardiovascular Disease

Tardif, Jean‐Claude; Heinonen, Therèse; Orloff, David G.; Libby, Peter

doi:10.1161/circulationaha.105.598987

Cited by 143 publications

(74 citation statements)

References 53 publications

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“…This method is well-established for assessment of endothelial function of conduit arteries 27,28 and has been used in previous own trials. 29,30 This noninvasive standard method is based on the application of a standardized hyperemic stimulus that induces a rapid dilation response of the brachial artery.…”

Section: Assessment Of Fmd Of the Brachial Arterymentioning

confidence: 99%

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

Kapiotis

Holzer

Schaller

et al. 2006

ATVB

193

149

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Background-Obesity is generally accepted as a risk factor for premature atherosclerosis. Subclinical inflammation as quantified by blood levels of C-reactive protein (CRP) contributes to the development and progression of atherosclerosis. We hypothesized that inflammation in obese children is related to functional and early morphological vascular changes. Methods and Results-Blood levels of high sensitivity (hs) CRP, hsIL-6, the soluble intercellular adhesion molecule1 (ICAM-1), vascular cell adhesion molecule (VCAM)-1, and E-selectin were measured in 145 severely obese (body mass index [BMI], 32.2Ϯ5.8 kg/m 2 ) and 54 lean (BMI, 18.9Ϯ3.2 kg/m 2 ) children 12Ϯ4 years old. Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measured by high-resolution ultrasound as markers of early vascular changes were assessed in 92 (77 obese and 15 lean) and 59 (50 obese and 9 lean) children, respectively. Obese children had significantly higher levels of hsCRP, hsIL-6, and E-selectin than healthy controls (4.1Ϯ4.8 versus 0.9Ϯ1.5 mg/L, PϽ0.001 for hsCRP; 1.99Ϯ1.30 versus 1.42Ϯ1.01 pg/mL, Pϭ0.05 for hsIL-6; and 78Ϯ38 versus 59Ϯ29 ng/mL, Pϭ0.01 for E-selectin). There were no differences in the levels of ICAM-1 and VCAM-1 between groups. Obese children had lower peak FMD response (7.70Ϯ6.14 versus 11.06Ϯ3.07%, Pϭ0.006) and increased IMT (0.37Ϯ0.04 versus 0.34Ϯ0.03 mm, Pϭ0.03) compared with controls. Morbidly obese children (nϭ14, BMI 44.1Ϯ3.9 kg/m 2 ) had highest levels of hsCRP (8.7Ϯ0.7 mg/L), hsIL-6 (3.32Ϯ1.1 pg/mL), and E-selectin (83Ϯ40 ng/mL). Conclusions-A proinflammatory state is detectable in obese children, which is accompanied by impaired vascular endothelial function and early structural changes of arteries, even in young subjects at risk. It remains to be determined whether high hsCRP in obese children predicts cardiovascular events.

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Section: Assessment Of Fmd Of the Brachial Arterymentioning

confidence: 99%

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

Kapiotis

Holzer

Schaller

et al. 2006

ATVB

193

149

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“…Carotid intima media thickness (IMT) is an intermediate phenotype of atherosclerosis and one of the strongest predictors of cardiovascular events, including myocardial infarction and stroke (12). Reduction in IMT over time entails a parallel decrease in the risk for cardiovascular events, and this parameter is considered as a valid surrogate end point by the Food and Drug Administration (13) and the European Medicines Agency (14). The validity of IMT as a cardiovascular risk biomarker in the CKD population is supported by studies in patients with predialysis CKD (15) and patients on dialysis (6,16).…”

Section: Introductionmentioning

confidence: 99%

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

Yılmaz

Sönmez

Sağlam

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives The role of reversibility of nontraditional risk factors, like inflammation and CKDmineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined.Design, setting, participants, and measurements The longitudinal relationship between C-reactive protein, CKDmineral bone disorder biomarkers, and intima media thickness was investigated in a series of 178 patients (age=32610 years) with stage 5 CKD maintained on chronic dialysis who underwent echo-color Doppler studies of the carotid arteries before and after renal transplantation. Smokers and patients with diabetes were excluded from the study. In all patients, immunosuppression was performed by a standard regimen on the basis of calcineurin inhibitors. Healthy controls were specifically selected to match the age and sex distribution of the patients. Biochemical and intima media thickness assessments were repeated 6 months after transplantation.Results Before transplantation, intima media thickness in patients with stage 5 CKD on dialysis (average=0.960.2 mm) was higher (P,0.001) than in well matched healthy controls (0.660.1 mm) and reduced substantially (222%; 95% confidence interval, 224% to 220%) after transplantation (P=0.001). GFR (multivariable-adjusted b=0.23; P,0.001), C-reactive protein (b=0.15; P,0.001), and fibroblast growth factor 23 (b=0.28; P,0.001) were the strongest independent correlates of intima media thickness before transplantation. Similarly, longitudinal changes in the same biomarkers were the sole independent correlates of simultaneous changes in intima media thickness (C-reactive protein: b=0.25; fibroblast growth factor 23: b=0.26; P,0.001 for both) after renal transplantation. The evolution of intima media thickness after transplantation was largely independent of classic risk factors, including BP, LDL cholesterol, and insulin resistance, as measured by homeostatic model assessment.Conclusions Intima media thickness improves after renal transplantation. Such an improvement associates with parallel changes in serum C-reactive protein and fibroblast growth factor 23. These observations are in keeping with the hypothesis that the decline in cardiovascular risk after transplantation, in part, depends on partial resolution of nontraditional cardiovascular risk factors, like inflammation and CKD-mineral bone disorder.

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“…Previous studies proved that CIMT is an early marker of atherosclerosis [22]. Measurement of CIMT is widely used and predicts cardiovascular events in subjects without clinically evident disease [23]. Hence, CIMT thickening is found when the vessels develop atherosclerosis and becomes stiffer.…”

Section: Discussionmentioning

confidence: 99%

The Relation between the New Clinical Parameter “Oscillatory Gap” and Carotid Intima Media Thickness as a Marker for Atherosclerosis

Tahlawi¹,

Elmurr²,

Sakrana³

et al. 2017

Arch Clin Hypertens

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Introduction: Carotid intima media thickness (CIMT) is an early ultrasonographic marker of atherosclerosis. A new clinical marker "oscillatory gap" (OG) was found to increase with advanced atherosclerosis. Aim:We aim to fi nd a relationship between this clinical marker, OG, and a known ultrasonographic marker of atherosclerosis as CIMT. Patients and Methods:Patients who underwent ultrasonographic assessment of CIMT in our center due to different indications were enrolled. The blood pressure (BP) of all cases was measured. The oscillatory systolic BP (OSBP) was defi ned as the point at which the mercury starts to oscillate. The auscultatory systolic BP (AUSBP) was defi ned as fi rst KorotKoff sound. The difference between OSBP and AUSBP was calculated for OG. The correlation between OG and the CIMT was statistically calculated. Results:The study comprised 85 patients with mean age 61.7±12.9 years. They included 47 patients with signifi cant OG (≥ 10 mmHg) and 38 patients with non-signifi cant gap (<10 mmHg). There was a signifi cant correlation between OG and CIMT (p<0.05). There was a highly signifi cant difference between both groups regarding CIMT (p=0.000). A cutoff value of 10mmHg for OG could predict increased CIMT≥8mm with a sensitivity of 92% and specifi city of 85%.Conclusion: OG could be a marker of advanced atherosclerosis. It correlates signifi cantly with CIMT. A cutoff value of 10mmHg of OG can predict CIMT≥8mm. Clinical Image

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Vascular Biomarkers and Surrogates in Cardiovascular Disease

Cited by 143 publications

References 53 publications

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

The Relation between the New Clinical Parameter “Oscillatory Gap” and Carotid Intima Media Thickness as a Marker for Atherosclerosis

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