Reductions in arterial stiffness with weight loss in overweight and obese young adults: Potential mechanisms

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Epidemiology Data Center, 130 DeSoto St., Pittsburgh, PA 15261, USA.
Atherosclerosis (Impact Factor: 3.99). 05/2012; 223(2):485-90. DOI: 10.1016/j.atherosclerosis.2012.05.022
Source: PubMed


Arterial stiffness decreases with weight loss in overweight/obese young adults. We aimed to determine the mechanisms by which this occurs.
We evaluated carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) in 344 young adults (23% male, BMI 25-40 kg/m(2)) at baseline, 6, and 12 months in a behavioral weight loss intervention. Linear mixed models were used to evaluate associations between weight loss and arterial stiffness and to examine whether improvements in obesity-related factors explained these associations.
At 6 months (7% mean weight loss), there was a significant median decrease of 47.5 cm/s in cfPWV (p < 0.0001) and a mean decrease of 11.7 cm/s in baPWV (p = 0.049). At 12 months (6% mean weight loss), only cfPWV remained reduced. In models adjusting for changes in mean arterial pressure and obesity-related factors, changes in BMI (p = 0.01) and common carotid artery diameter (p = 0.003) were positively associated with change in cfPWV. Reductions in heart rate (p < 0.0001) and C-reactive protein (p = 0.02) were associated with reduced baPWV and accounted for the association between weight loss and reduced baPWV.
Weight loss is associated with reduced cfPWV independently of changes in established hemodynamic and cardiometabolic risk factors, but its association with reduced baPWV is explained by concurrent reductions in heart rate and inflammation.

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    • "While neither RAAS, NO nor SNS activity can explain our results, we postulate that changes in arterial stiffness with empagliflozin are due to several other factors (Figure 1). First, weight loss independently decreases blood pressure and arterial stiffness [49]. Empagliflozin was associated with a significant reduction in weight of 2.7 kg in our cohort and this may have contributed to benefits on blood pressure and arterial stiffness, as previously reported [22,24]. "
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    ABSTRACT: Individuals with type 1 diabetes mellitus are at high risk for the development of hypertension, contributing to cardiovascular complications. Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness, and is an important contributing factor for hypertension. Since the sodium glucose cotransport-2 (SGLT2) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus, we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity. Blood pressure, arterial stiffness, heart rate variability (HRV) and circulating adrenergic mediators were measured during clamped euglycaemia (blood glucose 4-6 mmol/L) and hyperglycaemia (blood glucose 9-11 mmol/L) in 40 normotensive type 1 diabetes mellitus patients. Studies were repeated after 8 weeks of empagliflozin (25 mg once daily). In response to empagliflozin during clamped euglycaemia, systolic blood pressure (111+/-9 to 109+/-9 mmHg, p = 0.02) and augmentation indices at the radial (-52%+/-16 to -57%+/-17, p = 0.0001), carotid (+1.3+/-17.0 to -5.7+/-17.0%, p < 0.0001) and aortic positions (+0.1+/-13.4 to -6.2+/-14.3%, p < 0.0001) declined. Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition. Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions (p <= 0.0001), while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia (5.7+/-1.1 to 5.2+/-0.9 m/s, p = 0.0017). HRV, plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions. Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects. The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition, including glucose lowering, antihypertensive and weight reduction effects.Trial registration: Clinical trial registration: NCT01392560.
    Full-text · Article · Jan 2014 · Cardiovascular Diabetology
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    • "Weight loss has been previously shown to improve vascular stiffness [9,15] although the mechanism underlying this association is unknown. Previous work from the SAVE trial has studied various predictors of changes in pulse-wave velocity [9]. "
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    ABSTRACT: Background: Chronic arterial stiffness contributes to the negative health effects of obesity and insulin resistance, which include hypertension, stroke, and increased cardiovascular and all-cause mortality. Weight loss and improved insulin sensitivity are individually associated with improved central arterial stiffness; however, their combined effects on arterial stiffness are poorly understood. The purpose of this study was to determine how insulin levels modify the improvements in arterial stiffness seen with weight loss in overweight and obese young adults. Methods: To assess the effects of weight loss and decreased fasting insulin on vascular stiffness, we studied 339 participants in the Slow the Adverse Effects of Vascular Aging (SAVE) trial. At study entry, the participants were aged 20-45, normotensive, non-diabetic, and had a body-mass index of 25-39.9 kg/m2. Measures of pulse wave velocity (PWV) in the central (carotid-femoral (cfPWV)), peripheral (femoral-ankle (faPWV)), and mixed (brachial-ankle (baPWV)) vascular beds were collected at baseline and 6 months. The effects of 6-month change in weight and insulin on measures of PWV were estimated using multivariate regression. Results: After adjustment for baseline risk factors and change in systolic blood pressure, 6-month weight loss and 6-month change in fasting insulin independently predicted improvement in baPWV but not faPWV or cfPWV. There was a significant interaction between 6-month weight change and change in fasting insulin when predicting changes in baPWV (p < 0.001). Individuals experiencing both weight loss and insulin reductions showed the greatest improvement in baPWV. Conclusions: Young adults with excess weight who both lower their insulin levels and lose weight see the greatest improvement in vascular stiffness. This improvement in vascular stiffness with weight loss and insulin declines may occur throughout the vasculature and may not be limited to individual vascular beds.
    Full-text · Article · Sep 2012 · Cardiovascular Diabetology
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