There are conflicting data on whether variations of physiologic cortisol levels associated with cardiovascular risk. We hypothesize that prior discordant findings are related to problems associated with varying sample size, techniques for assessing cardiovascular risk and failure to adequately account for environmental factors. To address these issues, we utilized a large sample size, selected the Framingham risk score to compute cardiovascular risk and performed the study in a highly controlled setting. We had two main objectives: determine whether higher, yet physiologic, cortisol levels associated with increased cardiovascular risk and determine whether caveolin-1 (rs926198) risk allele carriers associated with increased cardiovascular risk. This was a cross-sectional study of 574 non-diabetic individuals who completed a common protocol. Data collection included fasting blood samples, blood pressure measurements and a 24-h urine-free cortisol collection. Five hundred seventeen of these participants also completed caveolin-1 genotyping. Subjects were classified as belonging to either the low-mode or high-mode urine-free cortisol groups, based on the bimodal distribution of urine-free cortisol. In multivariate analysis, Framingham risk score was statistically higher in the high-mode cortisol group (10.22 (mean) ± 0.43 (s.e.m.)) compared to the low-mode cortisol group (7.73 ± 0.34), P < 0.001. Framingham risk score was also statistically higher in the caveolin-1 risk allele carriers (8.91 ± 0.37) compared to caveolin-1 non-risk allele carriers (7.59 ± 0.48), P = 0.034. Overall, the estimated effect on Framingham risk score of carrying the caveolin-1 risk allele was 1.33 ± 0.61, P = 0.029. Both urinary cortisol and caveolin-1 risk allele status are independent predictors of Framingham risk score.
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Andrea V Haas, Paul N Hopkins, Nancy J Brown, Luminita H Pojoga, Jonathan S Williams, Gail K Adler, and Gordon H Williams
Milica Popovic, Fahim Ebrahimi, Sandrine Andrea Urwyler, Marc Yves Donath, and Mirjam Christ-Crain
Arginine vasopressin (AVP) was suggested to contribute to cardiovascular risk and type 2 diabetes in patients with metabolic syndrome. The proinflammatory cytokine interleukin (IL)-1 is able to induce AVP secretion and plays a causal role in cardiovascular mortality and type 2 diabetes. We investigated in two studies whether copeptin levels – the surrogate marker for AVP – are regulated by IL-1-mediated chronic inflammation in patients with metabolic syndrome. Study A was a prospective, interventional, single-arm study (2014–2016). Study B was a randomized, placebo-controlled, double-blind study (2016–2017). n = 73 (Study A) and n = 66 (Study B) adult patients with metabolic syndrome were treated with 100 mg anakinra or placebo (only in study B) twice daily for 1 day (study A) and 28 days (study B). Fasting blood samples were drawn at day 1, 7, and 28 of treatment for measurement of serum copeptin. Patients with chronic low-grade inflammation (C-reactive protein levels ≥2 mg/L) and BMI >35 kg/m2 had higher baseline copeptin levels (7.7 (IQR 4.9–11.9) vs 5.8 (IQR 3.9–9.3) pmol/L, P inflamm = 0.009; 7.8 (IQR 5.4–11.7) vs 4.9 (IQR 3.7–9.8) pmol/L, P BMI = 0.008). Copeptin levels did not change either in the anakinra or in the placebo group and remained stable throughout the treatment (P = 0.44). Subgroup analyses did not reveal effect modifications. Therefore, we conclude that, although IL-1-mediated inflammation is associated with increased circulating copeptin levels, antagonizing IL-1 does not significantly alter copeptin levels in patients with metabolic syndrome.
Valeria Hirschler, Claudia Molinari, Silvia Lapertosa, Gustavo Maccallini, and Claudio D Gonzalez
The association between central obesity and cardiometabolic complications justifies exploring its association in normal-weight and overweight/obese (OW/OB) schoolchildren.
To describe cardiometabolic markers in four groups according to BMI/WC categories: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB, in a sample of Argentinean schoolchildren.
A cross-sectional study of 1264 Argentinean schoolchildren (624 F), aged 9.5 ± 2.2 years was performed between November 2013 and 2015. Children’s anthropometric measures, blood pressure (BP), glucose, lipids, and insulin were measured. Children were divided into four groups: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB.
The prevalence of normal-weight children without central OB was 64.3% (796), normal weight with central OB 5% (66), OW/OB without central OB 11% (137), and OW/OB with central OB 21% (265). Normal weight with central OB had significantly higher triglycerides than normal-weight children without central OB (86 vs 70 mg/dL, respectively) and OW/OB children without central OB (81 vs 77 mg/dL). Multiple linear regression analyses showed that age, systolic BP, HDL-C, triglycerides, and maternal WC were significantly associated with children’s WC; R2 = 0.50 as well as children’s BMI; R2 = 0.37.
This study found that children with central OB might be at future higher cardiometabolic risk than those without central OB independently of the presence of OW/OB. However, future longitudinal studies should be performed to confirm these findings.
David J F Smith, Hemanth Prabhudev, Sirazum Choudhury, and Karim Meeran
Patients who need glucocorticoid replacement in both primary and secondary adrenal insufficiency (AI) have the choice of either once-daily prednisolone or thrice-daily hydrocortisone. A recent European study found no difference between prednisolone and hydrocortisone users in several markers including glucose, weight, body mass index, systolic and diastolic blood pressure and waist circumference, although an increase in cholesterol and low-density lipoprotein (LDL) was suggested in a subgroup of these patients. The aim of this study was to expand the evidence base for the use of these agents as replacement therapy.
Data from 82 patients on hydrocortisone and 64 patients on prednisolone for AI at Imperial College Healthcare NHS Trust were analysed.
There was no significant difference in total cholesterol, LDL levels or any other risk factors between hydrocortisone and prednisolone patients. Prednisolone was subjectively significantly more convenient than hydrocortisone (P = 0.048).
Prednisolone once daily is more convenient than hydrocortisone thrice daily, and there is no difference in the markers of cardiovascular risk measured. Because prednisolone mimics the circadian rhythm better than other glucocorticoids, it should be considered as an alternative to hydrocortisone for AI.
Chunliang Yang, Junyi Li, Fei Sun, Haifeng Zhou, Jia Yang, and Chao Yang
Hyperglycemia is the consequence of blood glucose dysregulation and a driving force of diabetic complications including retinopathy, nephropathy and cardiovascular diseases. The serum and glucocorticoid inducible kinase-1 (SGK1) has been suggested in the modulation of various pathophysiological activities. However, the role of SGK1 in blood glucose homeostasis remains less appreciated. In this review, we intend to summarize the function of SGK1 in glucose level regulation and to examine the evidence supporting the therapeutic potential of SGK1 inhibitors in hyperglycemia. Ample evidence points to the controversial roles of SGK1 in pancreatic insulin secretion and peripheral insulin sensitivity, which reflects the complex interplay between SGK1 activation and blood glucose fluctuation. Furthermore, SGK1 is engaged in glucose absorption and excretion in intestine and kidney and participates in the progression of hyperglycemia-induced secondary organ damage. As a net effect, blockage of SGK1 activation via either pharmacological inhibition or genetic manipulation seems to be helpful in glucose control at varying diabetic stages.
Jian Ding, Yan Kang, Yuqin Fan, and Qi Chen
Preeclampsia (PE) is a complication affecting pregnant women worldwide, which usually manifests as severe maternal hypertension. Resveratrol (RESV), a naturally existing polyphenol, is known to exhibit beneficial effects in cardiovascular disease including hypertension. We evaluated the outcome of treatment combining oral nifedipine (NIFE) and RESV against PE.
Design and methods
Using a randomized group assignment, 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo. Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis. Secondary endpoints were defined as the number of doses needed to control blood pressure, maternal and neonatal adverse effects.
Compared with the NIFE + placebo group, the time needed to control blood pressure was significantly reduced in NIFE + RESV group, while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group. The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group. No differences in maternal or neonatal adverse effects were observed between the two treatment groups.
Our data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients.
Hamidreza Mani, Yogini Chudasama, Michelle Hadjiconstantinou, Danielle H Bodicoat, Charlotte Edwardson, Miles J Levy, Laura J Gray, Janette Barnett, Heather Daly, Trevor A Howlett, Kamlesh Khunti, and Melanie J Davies
To evaluate the effectiveness of a structured education programmes in women with polycystic ovary syndrome (PCOS).
Single-centre, randomised controlled trial, testing a single exposure to a group-based, face-to-face, structured education programme. Inclusion criteria were women with PCOS, aged 18–49 years inclusive and body mass index ≥23 kg/m2 for black and minority ethnicities or ≥25 kg/m2 for white Europeans. Primary outcome was step-count/day at 12 months. Secondary outcomes included indices of physical activity, cardiovascular risk factors, quality of life (QoL) and illness perception (IP).
161 women were included (78 control, 83 intervention); 69% white; mean age 33.4 (s.d. 7.6) years, of whom 100 (48 intervention; 52 control) attended their 12-month visit (38% attrition). 77% of the intervention arm attended the education programme. No significant change in step-count was observed at 12 months (mean difference: +351 steps/day (95% confidence interval −481, +1183); P = 0.40). No differences were found in biochemical or anthropometric outcomes. The education programme improved participants’ IP in 2 dimensions: understanding their PCOS (P < 0.001) and sense of control (P < 0.01) and improved QoL in 3 dimensions: emotions (P < 0.05), fertility (P < 0.05), weight (P < 0.01) and general mental well-being (P < 0.01).
A single exposure to structured education programme did not increase physical activity or improve biochemical markers in overweight and obese women with PCOS. However, providing a structured education in parallel to routine medical treatment can be beneficial for participants’ understanding of their condition, reducing their anxiety and improving their QoL.
Yen Kheng Tan, Yu Heng Kwan, David Choon Liang Teo, Marieke Velema, Jaap Deinum, Pei Ting Tan, Meifen Zhang, Joan Joo Ching Khoo, Wann Jia Loh, Linsey Gani, Thomas F J King, Eberta Jun Hui Tan, Shui Boon Soh, Vanessa Shu Chuan Au, Tunn Lin Tay, Lily Mae Quevedo Dacay, Keng Sin Ng, Kang Min Wong, Andrew Siang Yih Wong, Foo Cheong Ng, Tar Choon Aw, Yvonne Hui Bin Chan, Khim Leng Tong, Sheldon Shao Guang Lee, Siang Chew Chai, and Troy Hai Kiat Puar
In addition to increased cardiovascular risk, patients with primary aldosteronism (PA) also suffer from impaired health-related quality of life (HRQoL) and psychological symptoms. We assessed for changes in HRQoL and depressive symptoms in a cohort of Asian patients with PA, after surgical and medical therapy.
Thirty-four patients with PA were prospectively recruited and completed questionnaires from 2017 to 2020. HRQoL was assessed using RAND-36 and EQ-5D-3L, and depressive symptoms were assessed using Beck Depression Inventory (BDI-II) at baseline, 6 months, and 1 year post-treatment.
At 1 year post-treatment, significant improvement was observed in both physical and mental summative scores of RAND-36, +3.65, P = 0.023, and +3.41, P = 0.033, respectively, as well as four subscale domains (physical functioning, bodily pain, role emotional, and mental health). Significant improvement was also seen in EQ-5D dimension of anxiety/depression at 1 year post-treatment. Patients treated with surgery (n = 21) had significant improvement in EQ-5D index score post-treatment and better EQ-5D outcomes compared to the medical group (n = 13) at 1 year post-treatment. 37.9, 41.6 and 58.6% of patients had symptoms in the cognitive, affective and somatic domains of BDI-II, respectively. There was a significant improvement in the affective domain of BDI-II at 1 year post-treatment.
Both surgical and medical therapy improve HRQoL and psychological symptoms in patients with PA, with surgery providing better outcomes. This highlights the importance of early diagnosis, accurate subtyping and appropriate treatment of PA.
Johan Verhelst, Anders F Mattsson, Cecilia Camacho-Hübner, Anton Luger, and Roger Abs
Adult-onset growth hormone deficiency (AO-GHD) is associated with an increased prevalence of the metabolic syndrome (MetS).
To determine the effect of GH replacement on the prevalence of MetS in AO-GHD and to study the impact of MetS on the incidence of cardiovascular events during GH replacement.
Patients and methods
1449 AO-GHD patients (males 48.9%; mean age 48.9 ± 12.8 year) were retrieved from KIMS (Pfizer International Metabolic Database). The prevalence of MetS (using International Diabetes Federation criteria) and its components were calculated at baseline and after one year of GH replacement. The relative risk to develop cardiovascular events according to the presence of MetS at baseline was assessed in another group of 3282 patients after prolonged GH replacement.
The prevalence of MetS was 46.9% at baseline and 48.2% after one year of GH replacement (P = NS). The percentage of patients with abnormal waist circumference decreased significantly (80.3 vs 77.4%; P < 0.001), but impaired glucose metabolism (17.1 vs 23.3%; P < 0.001) increased and HDL cholesterol (48.2 vs 50.9%; P = 0.011) decreased. Switch from MetS to NoMS (18.5%) and from NoMS to MetS (18.8%) occurred. All patients showed a significant and comparable amelioration of quality of life. During seven years of GH replacement patients with MetS had a 66% higher risk (P = 0.0016) to develop a new coronary disease compared to NoMS.
MetS prevalence remains unchanged in AO-GHD during one year of GH replacement whereas its components are differentially affected. Besides GH replacement, consequent pharmacotherapy of all risk factors and endorsement of lifestyle intervention appears to be of uttermost importance together with early GHD diagnosis to prevent cardiovascular disease during prolonged treatment.
Jie Shi, Zhen Yang, Yixin Niu, Weiwei Zhang, Ning Lin, Xiaoyong Li, Hongmei Zhang, Hongxia Gu, Jie Wen, Guang Ning, Li Qin, and Qing Su
A small thigh circumference is associated with an increased risk of diabetes, cardiovascular diseases, and total mortality. The purpose of this study was to evaluate the association between thigh circumference and hypertension in the middle-aged and elderly population.
A total of 9520 individuals aged 40 years and older with measurement of thigh circumference were available for analysis. The measurement of thigh circumference was performed directly below the gluteal fold of the thigh. The association of thigh circumference with hypertension was tested in logistic regression analyses and reported as odds ratio (OR) with 95% CI.
Thigh circumference was negatively correlated with systolic blood pressure, diastolic blood pressure, fasting glucose, and total cholesterol. Compared with the lowest thigh circumference tertile group, the risk of hypertension was significantly lower in the highest tertile group, both in overweight individuals (OR 0.68; 95% CI 0.59–0.79, P < 0.001) and obese individuals (OR 0.51; 95% CI 0.38–0.70, P < 0.001).
In the present study, large thigh circumference is associated with lower risk of hypertension in overweight and obese Chinese individuals.