Endothelial Dysfunction and Low-Grade Inflammation Are Associated With Greater Arterial Stiffness Over a 6-Year Period

Bussel, Bas C. van; Schouten, F.J.M.; Henry, Ronald M.A.; Schalkwijk, Casper G.; Boer, Michiel R. de; Ferreira, Isabel; Smulders, Yvo M.; Twisk, Jos W. R.; Stehouwer, Coen D. A.

doi:10.1161/hypertensionaha.111.174557

Cited by 142 publications

(114 citation statements)

References 46 publications

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“…Therefore, it is hard to understand whether the aforementioned relationships were indeed causal. Our results, along with those of others 16,18) , suggest that inflammation may not influence arterial stiffness over time.…”

Section: Discussionsupporting

confidence: 84%

“…Tomiyama et al reported that changes in heart rate, but not changes in C-reactive protein were associated with increases in PWV in middle-aged Japanese adults over a 5-6-year time period 16) . Similarly, Benetos et al noted that changes in SBP and HR were determinants of change in PWV over 6 years in normotensive and treated hypertensive adults 17) , while van Bussel et al recently noted no association of the change in inflammation with the change in PWV over a 6-year period 18) . Taken together, these findings suggest that pulsatile stress and peak wall stress (i.e.…”

Section: Resultsmentioning

confidence: 98%

“…Pulse wave velocity is associated with an increased risk of cardiovascular disease events and a better understanding of the risk factors for increased arterial stiffness over time might help in the determi- 6-year period 23) . Although McEniery et al noted an association between central PWV and change in C-reactive protein using a 20-year long-term followup study design, investigators did not measure PWV at baseline (thus, the change in PWV over time could not be ascertained).…”

Section: Discussionmentioning

confidence: 99%

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Pulsatile Stress, Inflammation and Change in Arterial Stiffness

Jae

Heffernan

Yoon

et al. 2012

JAT

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Aim: Understanding factors that contribute to changes in arterial stiffness over time is important as this may lead to therapies that can abrogate cardiovascular risk. We compared the contribution of pulsatile stress and inflammation to changes in arterial stiffness in middle-aged men using a 1-year follow-up study design. Methods: Arterial stiffness was derived from brachial-ankle pulse wave velocity (baPWV) in 107 men (mean age 53±6 yrs) on two separate occasions. The changes in outcome variables were calculated as the difference between the first and second examinations (mean interval 403±122 days). Pulsatile stress was calculated as the product of heart rate and brachial pulse pressure. C-reactive protein (CRP), white blood cell count (WBC) and fibrinogen were measured as inflammatory markers. Pulse wave velocity (PWV), an index of arterial stiffness, is associated with coronary atherosclerosis 1) and increased risk of cardiovascular (CV) events and mortality [2][3][4] , and lowering PWV with therapeutic intervention reduces CV risk 5) . Despite the clinical significance of PWV as a measure of CV risk, the mechanisms that contribute to changes in PWV remain poorly understood. It is often suggested that arterial stiffness is the integration of CV risk factors on the vessel wall over time 6) . Yet while numerous cross-sectional studies have noted that age and blood pressure are strong predictors of PWV 7,8) , other traditional CVD risk factors do not seem to play an integral role in modulating arterial stiffness 9) ; that is, the association of factors such as lipids, diabetes, sex, smoking and BMI with PWV is weak or insignificant, suggesting the dissociation of traditional risk factors and PWW 9) . Individual risk factors can fluctuate over time and their values, recorded at the time of risk assessment, may not reflect their true impact on the arterial wall 10) . Non-traditional CV risk factors may offer insight

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Section: Discussionsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Pulsatile Stress, Inflammation and Change in Arterial Stiffness

Jae

Heffernan

Yoon

et al. 2012

JAT

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“…The mean BMI was profoundly higher compared with the BMI of 24.4 kg/m 2 in a healthy Dutch cohort of 4070 men and women with a comparable mean age (25). By comparing all cardiovascular risk factors with a different Dutch cohort of 293 healthy subjects of similar age, we (data not shown) demonstrated a worse metabolic profile in our GH-deficient population (26). However, due to a narrow range of age in this cohort of healthy subjects, the data have to be interpreted with caution.…”

Section: Discussionmentioning

confidence: 57%

Effect of long-term GH replacement therapy on cardiovascular outcomes in isolated GH deficiency compared with multiple pituitary hormone deficiencies: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults

Bunderen

Dries

Heymans

et al. 2014

European Journal of Endocrinology

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Objective: Isolated GH deficiency (IGHD) could provide a model to investigate the influence of GH deficiency per se and the effect of GH replacement therapy without the influence from other pituitary hormone deficiencies or their treatment. The aim of this study is to address the questions about differences between IGHD and multiple pituitary hormone deficiencies (MPHDs) in clinical presentation and in responsiveness to GH treatment. Design: A nationwide surveillance study was carried out to describe the difference in the clinical presentation and responsiveness to GH treatment of patients with IGHD and MPHDs. Methods: The Dutch National Registry of GH Treatment in Adults was founded in 1998 to gain more insight into long-term efficacy and safety of GH therapy. Out of 2891 enrolled patients, 266 patients with IGHD at the start of GH treatment were identified and compared with 310 patients with MPHDs. Cardiovascular indices will be investigated at baseline and during long-term follow-up, including body composition, lipid profile, glucose metabolism, blood pressure, and morbidity. Results: Patients with IGHD and MPHDs were demonstrated to be different entities at clinical presentation. Metabolically, patients with MPHDs had a larger waist circumference, lower HDL cholesterol level, and higher triglyceride level. The effect of GH treatment was comparable between patient groups. GH seems to protect against rising lipid levels and blood pressure, even after excluding patients using corresponding concomitant medication. The risk for cardiovascular disease or diabetes mellitus during follow-up was not different between patients with IGHD and MPHDs. Conclusions: Patients with IGHD had a less impaired metabolic profile than patients with MPHDs at baseline. Influence of other pituitary hormone replacement therapies on the effect of GH treatment is not demonstrated.

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“…Thus the variations in these factors between men and women may simply relate to variations in sex hormones as opposed to age or fitness. In any case, the higher ICAM1 and p-selectin concentrations demonstrated in men puts them at higher risk for cardiovascular disease than women [8,63].…”

Section: Discussionmentioning

confidence: 94%

Changes in Endothelial Markers during a Summer Ultra-Endurance Road Cycling Event in the Heat

BR¹

2016

Int J Sports Exerc Med

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Purpose: To assess the impact of completing a 164 km road cycling event performed in a hot environment (Wichita Falls, Texas in August), on endothelial biomarkers and resultant risk of blood clots in men and women.Methods: 37 event participants (28 men and 9 women; 51.8 ± 9.5 y) completed the ride. Plasma samples were collected in the morning before (PRE) and immediately after (IP) completing the ride. Concentrations of endothelial cell markers -endothelin-1 (ET-1), p-selectin, and intercellular adhesion molecule 1 (ICAM1), were measured and associations between changes from PRE-to IP-ride were examined as a function of race event completion time and participant characteristics (demographics and anthropometrics). Results:All of the endothelial cell markers (ET-1, p-selectin, and I-CAM1) increased significantly from PRE to IP. After controlling for PRE values, completion time was positively correlated with ET-1 (r = 0.42, p < 0.01) and negatively related to p-selectin (r = -0.42, p < 0.05). Waist circumference was positively related to ICAM1 (r = 0.34, p < 0.01). In addition, males had greater concentrations of ICAM1 (d = 1.32, p < 0.01) and p-selectin (d = 0.84, p < 0.05) than females. Conclusion:Completing a 164 km road cycling event in hot conditions resulted in increased concentrations of endothelial cell markers in men and women. Although this result may suggest endothelial cell injury, it is unclear whether this response is indicative of an increased risk of blood clot formation.

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Endothelial Dysfunction and Low-Grade Inflammation Are Associated With Greater Arterial Stiffness Over a 6-Year Period

Cited by 142 publications

References 46 publications

Pulsatile Stress, Inflammation and Change in Arterial Stiffness

Pulsatile Stress, Inflammation and Change in Arterial Stiffness

Effect of long-term GH replacement therapy on cardiovascular outcomes in isolated GH deficiency compared with multiple pituitary hormone deficiencies: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults

Changes in Endothelial Markers during a Summer Ultra-Endurance Road Cycling Event in the Heat

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