Abstract 3519: Modest Fat Gain Causes Endothelial Dysfunction In Lean Healthy Humans: A Randomized Blinded Controlled Trial

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Abel Romero Corral ◽  
Justo Sierra-Johnson ◽  
Marek Orban ◽  
Apoor S Gami ◽  
Fatima H Sert Kuniyoshi ◽  
...  

Background: Endothelial dysfunction assessed by flow mediated dilation (FMD) of the brachial artery has been identified as an independent predictor of cardiovascular events. However, whether weight gain impairs endothelial function is unknown. Methods: A randomized blinded controlled-trial to assess the effects of weight gain on endothelial function. After a weight maintenance period supervised by an experience dietitian, volunteers were randomized to gain weight (4 kg) or maintain weight. We recruited lean (BMI 18.5–24.9 kg/m 2 ) healthy volunteers (no diseases, medications and non-smokers) from the community. Using ultrasound, endothelial function was measured by FMD and non-flow mediated dilation (NFMD) of the brachial artery in the early morning (6:30 a.m.). Endothelial function was measured at baseline, after fat gain at 8 weeks and after weight loss at 16 weeks for fat-gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition techniques to measure body fat %, such as dual x-ray absorptiometry and abdominal CT scans were performed. Results: We recruited 35 fat-gainers and 8 weight maintainers. Mean age was 29 ± 6 years and 18 (42 %) were women. There were no differences in age, anthropometric and body composition measurements, blood pressure, heart rate or apnea hypopnea index at baseline between both groups. After an average gain of 4 kg, the fat-gainer group significantly increased their total, visceral and subcutaneous fat. Brachial artery FMD and NFMD remained unchanged in weight maintainers. However, it decreaed in fat-gainers (FMD=9.1 ± 3 vs. 7.6 ± 3.2, p=0.003 and NFMD=12.0 ± 4.9 vs. 10.1 ± 6.0, p=0.01), but recovered to baseline after subjects shed the gained weight (basleline vs. recovery: FMD=9.1 ± 3 vs. 9.0 ± 3, p=NS and NFMD =12.0 ± 4.9 vs.12.6 ± 5.0, p=NS). Visceral fat gain, but not subcutaneous fat gain was significantly correlated with the decrease in brachial artery FMD (rho =−0.42, p=0.004 and rho =−0.22, p=0.15, respectively). Conclusions: In lean healthy young subjects, modest weight gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial funcion recovers after weight loss. Viscerar rather than subcutaneous fat predicts endothelial dysfunction.

2014 ◽  
Vol 14 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Joana Adalgisa Furtado Magalhães Andrade ◽  
Francisco Herlânio Costa Carvalho ◽  
Rosa Maria Salani Mota ◽  
Guilherme Augusto Magalhães Andrade ◽  
Helvécio Neves Feitosa ◽  
...  

Objectives: to determine the prevalence of endothelial dysfunction and its association with a history of mild and severe preeclampsia in adolescents. Methods: a cross-sectional study was carried out at the MEAC-UFC with 103 primiparous adolescents postpartum. The assessment of endothelial function was performed by way of flow-mediated dilatation of the brachial artery. Variables (age, body mass index, gestational age at delivery, systolic and diastolic blood pressure and flow-mediated dilation) were compared between groups. p<0.05 was considered to be statistically significant. Results: twenty-four (23.3%) patients had preeclampsia (PE): 11 mild and 13 severe. The overall prevalence of endothelial dysfunction was 23.3% (21.5% of patients with normotensive pregnancies and 29.2% of the PE patients: 18.2% of those with mild PE and 38.5% of those with severe PE). The figures were statistically significant for systolic blood pressure, p=0.007. Conclusions: patients with a history of PE have higher systolic blood pressure than patients with a history of normotensive pregnancy, but did not have more endothelial dysfunction.


2018 ◽  
Vol 315 (4) ◽  
pp. H925-H933 ◽  
Author(s):  
Tessa E. Adler ◽  
Charlotte W. Usselman ◽  
Akira Takamata ◽  
Nina S. Stachenfeld

Hypertension, obesity, and endothelial function predict cardiovascular disease in women, and these factors are interrelated. We hypothesized that hypertension and obesity are associated with endothelial dysfunction in young women and that short-term ethinyl estradiol exposure mitigates this dysfunction. We examined flow-mediated dilation (FMD) responses before and during 7 days of oral ethinyl estradiol (30 µg/day) in 19 women (25 ± 5, 18–35 yr). We divided our sample into two groups based on two criteria: blood pressure and obesity. Women were divided into normal blood pressure (NBP; mean arterial pressure range: 78–91 mmHg, n = 7) and high blood pressure (HBP; mean arterial pressure range: 95–113 mmHg, n = 9) groups. We also stratified our subjects by body composition (lean: 18–31%, n = 8; obese: 38–59%, n = 9). We evaluated brachial FMD after two distinct shear stress stimuli: occlusion alone and occlusion with ischemic handgrip exercise. Obesity was unrelated to both FMD responses. Before ethinyl estradiol administration, the HBP group had blunted ischemic exercise responses relative to the NBP group (8.0 ± 3.5 vs. 12.3 ± 3.2%, respectively, P = 0.05). However, during ethinyl estradiol administration, ischemic exercise responses increased in the HBP group (12.8 ± 6.1%, P = 0.04) but decreased in the NBP group (5.6 ± 2.4%, P = 0.01). Standard FMD did not reveal differences between groups. In summary, 1) moderate HBP predicted endothelial impairment, 2) ethinyl estradiol administration had divergent effects on FMD in women with NBP versus HBP, and 3) enhanced FMD (ischemic handgrip exercise) revealed differences in endothelial function, whereas standard FMD (occlusion alone) did not. NEW & NOTEWORTHY We are the first to show that mild hypertension is a stronger predictor of endothelial dysfunction than obesity in healthy women without overt cardiovascular dysfunction. Importantly, the standard 5-min flow-mediated vasodilation stimulus did not detect endothelial dysfunction in our healthy population; only an enhanced ischemic handgrip exercise shear stress stimulus detected endothelial impairment. Estradiol administration increased flow-mediated dilation in women with high blood pressure, so it may be a therapeutic intervention to improve endothelial function.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Catharine Couch ◽  
Nikki Bush ◽  
Tanja Dudenbostel ◽  
Barbara Gower

Racial disparities in health outcomes continue to be a significant public health concern and African Americans (AA) are disproportionately burdened by several risk factors for cardiovascular disease. Endothelial dysfunction has been shown to be a predictor of CVD and metabolic factors, including insulin resistance, are associated with endothelial dysfunction. Compared to EA, AA have impaired endothelial function and are more insulin resistant (less insulin sensitive). However, it remains unclear how insulin resistance may contribute to endothelial dysfunction in AA and EA. The purpose of the present study was to evaluate the relationship between insulin sensitivity and endothelial function in AA and EA. It was hypothesized that insulin sensitivity would be associated with endothelial function in both AA and EA. Skeletal muscle insulin sensitivity was measured by hyperinsulinemic-euglycemic glucose clamp technique in 112 lean, overweight, and obese AA and EA adults without diabetes. Insulin was infused at 120 mU/m 2 /min for 3 hours and an infusion of 20% dextrose was adjusted to maintain blood glucose at the fasting level. Insulin sensitivity (10 -4 .dL.kg -1 .min -1 /(μU/mL)) was defined as M/(G x ΔI), where M is steady state glucose infusion rate, G is steady state serum glucose concentration, and ΔI is the difference between basal and steady state serum insulin concentrations. M was adjusted for total lean body mass which was measured by dual-energy X-ray absorptiometry (DXA). Endothelial function was assessed by percent change in flow-mediated brachial artery dilatation (FMD). Changes in brachial artery diameter during reactive hyperemia were measured using ultrasound. Increased blood flow was induced via blood pressure cuff around the forearm, with a 5-minute inflation at 50 mmHg above the subject’s systolic blood pressure. Brachial arterial flow was determined using a pulsed-Doppler signal at baseline and 10-15 seconds after cuff release. Arterial diameter was measured at end-diastolic phase from super-VHS recordings. For reactive hyperemia response, measurements with the 5 largest diameters were averaged and the percent increase from baseline was determined as FMD. A total of 55 AA and 57 EA were included in the analysis. Mean insulin sensitivity was 4.89 in AA and 7.97 in EA (p < .0001) and mean FMD was 10.69 in AA and 10.14 in EA (p = .595). Linear regression analysis indicated a significant relationship between insulin sensitivity and endothelial function in AA but not in EA (p= .005 and p= .5, respectively). These results suggest that insulin sensitivity may play a role in determining endothelial function in AA.


2015 ◽  
Vol 118 (12) ◽  
pp. 1510-1515 ◽  
Author(s):  
Evan L. Matthews ◽  
Michael S. Brian ◽  
Meghan G. Ramick ◽  
Shannon Lennon-Edwards ◽  
David G. Edwards ◽  
...  

Recent studies demonstrate that high dietary sodium (HS) impairs endothelial function in those with salt-resistant (SR) blood pressure (BP). The effect of HS on endothelial function in those with salt-sensitive (SS) BP is not currently known. We hypothesized that HS would impair brachial artery flow-mediated dilation (FMD) to a greater extent in SS compared with SR adults. Ten SR (age 42 ± 5 yr, 5 men, 5 women) and 10 SS (age 39 ± 5 yr, 5 men, 5 women) healthy, normotensive participants were enrolled in a controlled feeding study consisting of a run-in diet followed by a 7-day low dietary sodium (LS) (20 mmol/day) and a 7-day HS (300 mmol/day) diet in random order. Brachial artery FMD and 24-h BP were assessed on the last day of each diet. SS BP was individually assessed and defined as a change in 24-h mean arterial pressure (MAP) of >5 mmHg between the LS and HS diets (ΔMAP: SR −0.6 ± 1.2, SS 7.7 ± 0.4 mmHg). Brachial artery FMD was lower in both SS and SR individuals during the HS diet ( P < 0.001), and did not differ between groups ( P > 0.05) (FMD: SR LS 10.6 ± 1.3%, SR HS 7.2 ± 1.5%, SS LS 12.5 ± 1.7%, SS HS 7.8 ± 1.4%). These data indicate that an HS diet impairs brachial artery FMD to a similar extent in adults with SS BP and SR BP.


2016 ◽  
Vol 101 (7) ◽  
pp. 2751-2758 ◽  
Author(s):  
Cyndya A. Shibao ◽  
Jorge E. Celedonio ◽  
Claudia E. Ramirez ◽  
Latisha Love-Gregory ◽  
Amy C. Arnold ◽  
...  

Context: The scavenger receptor CD36 influences the endothelial nitric oxide-cGMP pathway in vitro. Genetic variants that alter CD36 level are common in African Americans (AAs), a population at high risk of endothelial dysfunction. Objective: To examine if the minor allele (G) of coding CD36 variant rs3211938 (G/T) which reduces CD36 level by approximately 50% influences endothelial function, insulin sensitivity (IS), and the response to treatment with the nitric oxide-cGMP potentiator sildenafil. Design: IS (frequently sampled iv glucose tolerance) and endothelial function (flow mediated dilation [FMD]) were determined in age- and body mass index-matched obese AA women with or without the G allele of rs3211938 (protocol 1). Effect of chronic sildenafil treatment on IS and FMD was tested in AA women with metabolic syndrome and with/without the CD36 variant, using a randomized, placebo-controlled trial (protocol 2). Setting: Two-center study. Participants: Obese AA women. Intervention: A total of 20-mg sildenafil citrate or placebo thrice daily for 4 weeks. Main outcome: IS, FMD. Results: G allele carriers have lower FMD (P = .03) and cGMP levels (P = .01) than noncarriers. Sildenafil did not improve IS, mean difference 0.12 (95% confidence interval [CI], −0.33 to 0.58; P = .550). However, there was a significant interaction between FMD response to sildenafil and rs3211938 (P = .018). FMD tended to improve in G carriers, 2.9 (95% CI, −0.9 to 6.8; P = .126), whereas it deteriorated in noncarriers, −2.6 (95% CI, −5.1 to −0.1; P = .04). Conclusions: The data document influence of a common genetic variant on susceptibility to endothelial dysfunction and its response to sildenafil treatment.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Fukumoto ◽  
Y Takemoto ◽  
J Yoshikawa ◽  
N Norioka ◽  
T Iguchi ◽  
...  

Abstract Background Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are well-known for preventing cardiovascular disease. Among n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play key roles in preventing cardiovascular diseases. However, the effects of n-3 PUFAs have been examined under conditions of simultaneous administration of EPA and DHA in the majority of clinical investigations and the effect of purified EPA is still controversial. EPA has been reported to improve endothelial dysfunction. Although several mechanisms underlying the effects of EPA on endothelial function have been demonstrated such as the modulation of lipid metabolism including increases in high-density lipoprotein (HDL) and/or decreases in triglyceride (TG) levels, decreases in cytokine production, and inhibition of inflammatory processes, the main mechanisms ameliorating endothelial function have not been fully determined. Purpose We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. Methods Fifty-one consecutive patients with hypertriglyceridemia (mean ± SD age, 60±13 years) with no evidence of coronary artery disease (CAD) were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-eight patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables such as body mass index, HbA1c, fasting glucose level, HDL, low-density lipoprotein, TG, systolic blood pressure, diastolic blood pressure, heart rate, interleukin-6, baseline diameter of the brachial artery, intima-media thickness of the brachial artery, and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed to examine the associations between FMD changes and clinical variables. Results FMD was significantly improved from 4.16% ± 1.88% to 6.30% ± 2.24% (p<0.0001) in the EPA group. The change in FMD was positively correlated with the change in EPA/arachidonic acid (AA) ratio (r=0.34, p=0.014). The multivariate regression analysis showed that the change in EPA/AA ratio alone was significantly associated with the change in FMD (p=0.010). Conclusions EPA treatment improves endothelial dysfunction in patients with hypertriglyceridemia without evidence of CAD. The change in FMD was associated with the change in EPA/AA ratio alone. These finding suggest that a direct effect of EPA on the endothelium may be the predominant factor ameliorating endothelial function. Acknowledgement/Funding This study was supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (15K08649).


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Naima Covassin ◽  
Prachi Singh ◽  
Fatima H Sert-Kuniyoshi ◽  
Abel Romero-Corral ◽  
Diane E Davison ◽  
...  

Introduction: Obesity is linked with heightened vulnerability to cardiovascular diseases including hypertension. Nonetheless, mechanistic studies addressing the effects of experimental weight gain on blood pressure are lacking. We sought to examine whether experimental weight gain raises ambulatory blood pressure in healthy individuals and identify any relationship between changes in blood pressure and changes in regional fat distribution. Methods: Twenty-six normal weight subjects were randomized to a 8-week period of weight gain through overfeeding (N=16; age 30.4±6.6 years, BMI 23.5±3.5 kg/m 2 ) or weight maintenance (N=10; age 27.1±7.7 years, BMI 23.6±2.7 kg/m 2 ). Measurements of body composition by dual-energy X-ray absorptiometry and abdominal computed tomographic scans and 24-h ambulatory blood pressure monitoring were obtained at baseline and at follow-up. Results: Overfeeding resulted in an increase in body weight of 3.7±1.5 kg ( p <0.001) in weight gainers, with increments seen in total (21994±8247.4 to 25180.7±8563.1 gr, p <0.001), visceral (61.6±32.7 to 75.5±30.9 cm 2 , p =0.002) and subcutaneous fat (135.5±77.4 to 167.9±82.9 cm 2 , p <0.001). No changes occurred in the maintenance group. Weight gainers exhibited an increase in 24-h systolic blood pressure at follow-up (113.7±8 to 117.7±7.9 mmHg, p =0.009) and mean blood pressure (MAP) (85.1±4.9 to 86.8±5.1 mmHg, p =0.02), while blood pressure was unchanged in controls. Changes in MAP were positively correlated only with changes in visceral fat (rho=0.452, p =0.02) but not with changes in weight or any other body composition measure. Conclusion: Modest weight gain leads to marked elevation in 24-h blood pressure in lean healthy subjects. The association between increased MAP and abdominal visceral fat accumulation suggests that visceral deposition of adipose tissue may contribute specifically and mechanistically to the enhanced risk of hypertension associated with weight gain.


2018 ◽  
Vol 88 (1-2) ◽  
pp. 80-89 ◽  
Author(s):  
Zahra Shakibay Novin ◽  
Saeed Ghavamzadeh ◽  
Alireza Mehdizadeh

Abstract. Branched chain amino acids (BCAA), with vitamin B6 have been reported to improve fat metabolism and muscle synthesis. We hypothesized that supplementation with BCAA and vitamin B6 would result in more weight loss and improve body composition and blood markers related to cardiovascular diseases. Our aim was to determine whether the mentioned supplementation would affect weight loss, body composition, and cardiovascular risk factors during weight loss intervention. To this end, we performed a placebo-controlled randomized clinical trial in 42 overweight and obese women (BMI = 25–34.9 kg/m2). Taking a four-week moderate deficit calorie diet (–500 kcal/day), participants were randomized to receive BCAA (6 g/day) with vitamin B6 (40 mg/day) or placebo. Body composition variables measured with the use of bioelectrical impedance analysis, homeostatic model assessment, and plasma insulin, Low density lipoprotein, High density lipoprotein, Total Cholesterol, Triglyceride, and fasting blood sugar were measured. The result indicated that, weight loss was not significantly affected by BCAA and vitamin B6 supplementation (–2.43 ± 1.02 kg) or placebo (–1.64 ± 1.48 kg). However, significant time × treatment interactions in waist to hip ratio (P = 0.005), left leg lean (P = 0.004) and right leg lean (P = 0.023) were observed. Overall, supplementation with BCAA and vitamin B6 could preserve legs lean and also attenuated waist to hip ratio.


Author(s):  
Katelyn J. Carey ◽  
Wendy Vitek

AbstractObesity, dieting, and weight cycling are common among reproductive-age women. Weight cycling refers to intentional weight loss followed by unintentional weight regain. Weight loss is accompanied by changes in gut peptides, adipose hormones, and energy expenditure that promote weight regain to a tightly regulated set point. While weight loss can improve body composition and surrogate markers of cardiometabolic health, it is hypothesized that the weight regain can result in an overshoot effect, resulting in excess weight gain, altered body composition, and negative effects on surrogate markers of cardiometabolic health. Numerous observational studies have examined the association of weight cycling and health outcomes. There appears to be modest association between weight cycling with type 2 diabetes mellitus and dyslipidemia in women, but no association with hypertension, cardiovascular events, and overall cancer risk. Interestingly, mild weight cycling may be associated with a decreased risk of overall and cardiovascular mortality. Little is known about the effects of weight cycling in the preconception period. Although obesity and weight gain are associated with pregnancy complications, preconception weight loss does not appear to mitigate the risk of most pregnancy complications related to obesity. Research on preconception weight cycling may provide insight into this paradox.


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