Independent Predictor Of Cardiovascular Risk Research Articles

Activation of CD137 signaling accelerates vascular calcification in vivo and vitro

ObjectivesVascular calcification is a characteristic feature of atherosclerosis and is considered as an independent predictor of cardiovascular risk. CD137 signaling has previously shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulation of vascular calcification has not been reported. In the present study, we investigated the effect of CD137 signaling on vascular calcification in ApoE−/− mice and in vascular smooth muscle cells (VSMCs) of mice. MethodsCalcium deposition and muscle fibers in vivo or vitro were identified by von-Kossa and Masson's trichrome staining respectively. Alkaline phosphatase (ALP) activity was measured by the ALP assay Kit. The presence of bone morphogenic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) was detected by real-time PCR, Western blot and immunofluorescence in vitro or vivo. ResultsOur data shows that activation of CD137 signaling by intraperitoneal injection of agonist-CD137 antibody increased the areas of vascular calcification. Activation of CD137 signaling also increased the expression of BMP2 and Runx2 in the atherosclerotic plaques. In vitro, activation of CD137 signaling also aggravated VSMC calcification, while blocking CD137 signaling could alleviate agonist-CD137 induced VSMC calcification. In addition, the levels of calcium, BMP2 and Runx2, indicators of calcification, were all significantly elevated in agonist-CD137 group in VSMCs. ConclusionOur data revealed a previously unrecognized role of CD137 signaling in vascular calcification in vivo and vitro and provides a novel target for prevention and treatment of atherosclerosis in the future.

Abstract P232: Psoriasis is Associated with Increased Arterial Stiffness: a Systematic Review and Meta-analysis

Background: Studies have shown that patients with psoriasis have higher risk of CVD, independent of traditional CVD risk factors. However, pathophysiology of the development of CVD in psoriasis is not well known. Arterial stiffness has been recognized as an independent predictor of cardiovascular risk. It is controversial whether psoriasis and arterial stiffness is associated. In this systematic review and meta-analysis, we sought to assess the hypothesis that patients with psoriasis have increased arterial stiffness compared with controls. Methods: Systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2016. We included original research publications that contained data on arterial stiffness and psoriasis. Aortic pulse wave velocity (aPWV) is the non-invasive marker for assessment of arterial stiffness. We compared aPWV between patients with psoriasis and controls and estimated the pooled mean difference (MD) and 95% confidence interval (CI) of aPWV using a random-effects model meta-analysis. Results: Data from five observational studies involving 438 participants (233 with psoriasis) were extracted and included in the meta-analysis. Pooled MD of aPWV was 1.17 m/sec higher in patients with psoriasis compared with controls (95% CI: 0.78-1.55, P-value<0.01, I 2 = 69%). There is no change in the direction or statistical significance of MD of aPWV after removing each study at a time in the sensitivity analysis. Conclusion: Psoriasis is associated with increased arterial stiffness. Assessment of arterial stiffness parameters may be important for early detection of cardiovascular deterioration in psoriasis patients.

PS 05-56 CENTRAL BLOOD PRESSURE AND WAVE REFLECTIONS AFTER FULL COURSE MARATHON RACE

Objective: Marathon running is aerobic and extremely vigorous exercise. Central blood pressure and wave reflections are independent predictors of cardiovascular risk. We investigated the acute effect of marathon race on central blood pressure and wave reflections. Design and Method: We studied 30 trained amateur marathoners (male n = 28, mean age = 51.6 ± 8.3 years). We measured central blood pressure and augmentation index before and immediate after the Seoul international marathon (18th March 2012). Central blood pressure and AIx (augmentation index) were measured using HEM-9000AI (Omron Healthcare Co., Ltd., Kyoto, Japan). Wilcoxon signed rank test was used to determine the difference between before and after race for blood pressure and AIx. Results: There is no significant change of brachial systolic and diastolic blood pressure before and after marathon. (p = 0.259, 0.494, respectively) However, there is a significant reduction of central systolic blood pressure after race (128.5 ± 16.8 to 115.5 ± 14.5 mmHg; p < 0.001). Marathon race caused a significant fall in both AIx (77.3 ± 11.3 to 57.4 ± 13.4 %; p < 0.001) and [email protected] (72.0 ± 9.3 to 58.1 ± 12.2 %; p < 0.001). Conclusions: The present study found a reduction in central systolic blood pressure without changes of brachial blood pressure. A significant fall in wave reflections was observed after marathon race. There were more or less acute beneficial effects of marathon on cardiovascular system contrary to our concern.

Comparative Study of the Efficacy of Olmesartan/Amlodipine vs. Perindopril/Amlodipine in Peripheral and Central Blood Pressure Parameters After Missed Dose in Type 2 Diabetes

Central aortic blood pressure (CBP) and CBP-derived parameters are independent predictors of cardiovascular risk. Angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors plus calcium channel blockers are the recommended first-line treatments in hypertensive diabetic patients; however, the effect in reducing CBP when a dose is skipped has not been established yet. The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine (OLM/AML) provides equal efficacy and safety as the perindopril/AML (PER/AML) combination in reducing CBP, augmentation index (AIx), and pulse wave velocity (PWV) when a drug dose is missed. In this noninferiority, randomized, double-blind, double-dummy parallel group, controlled design trial, 88 patients received either OLM 20-40mg/AML 5-10mg (41 patients) or PER 4-8mg/AML 5-10mg (47 patients) for 24 weeks. The main endpoint was the aortic systolic BP (SBP) after 24 weeks of treatment at 48 hours from the last administration. The OLM/AML combination reached the noninferiority criteria in reducing central systolic BP after 24 weeks of treatment and after the missed dose, compared to the PER/AML combination (-17 and -8mm Hg, respectively). Peripheral BP, AIx, and PWV were significantly lower in both groups after 24 weeks of treatment and 48 hours after the missed dose, observing a trend to a greater reduction in CBP-derived parameters in the OLM/AML group. The OLM/AML combination is safe, well tolerated, and not inferior to the combination of PER/AML in lowering CBP and CBP-derived parameters in diabetic patients. OLM/AML provides longer-lasting efficacy in terms of CBP reduction compared to PER/AML.

Renal Ultrasound (and Doppler Sonography) in Hypertension: An Update.

Ultrasound (US) allows the non-invasive evaluation of morphological changes of kidney structure (by means of B-Mode) and patterns of renal and extrarenal vascularization (by means of color-Doppler and contrast-enhanced US). In hypertensive subjects it offers a relevant contribution to the diagnosis of early renal damage, acute or chronic nephropathies and nephrovascular disease. However, morphological changes are often detected late and non-specific and in recent years evidence has increased regarding the clinical relevance of renal resistive index (RRI) for the study of vascular and renal parenchymal renal abnormalities. RRI is measured by Doppler sonography in an intrarenal artery, as the difference between the peak systolic and end-diastolic blood velocities divided by the peak systolic velocity. At first RRI was proved to be a marker of renal disease onset and progression; later the influence of systemic vascular properties on RRI was shown and authors claimed its use as an independent predictor of cardiovascular risk rather than of renal damage. Indeed, renal vascular resistance is only one of several renal (vascular compliance, interstitial and venous pressure), and extrarenal (heart rate, pulse pressure) determinants that concur to determine RRI individual values but not the most important one. The clinical relevance of RRI measurement as a surrogate endpoint of specific renal damage or/and as surrogate endpoint of atherosclerotic diffuse vascular damage is still debated.To summarize, from the literature: (a) In hypertensives with normal renal function and no albuminuria, especially in younger people, RRI is an early marker of renal damage that is especially useful when hypertension and diabetes concur in the same subjects. In these subjects RRI could improve current clinical scores used to stratify early renal damage. In older subjects RRI increases in accordance with the increase in systemic vascular stiffness and, because of this close relationship, RRI is also a marker of systemic atherosclerotic burden and the role of renal determinants can weaken. The clinical relevance was not specifically investigated. (b) In transplant kidney and in chronic renal disease high (>0.80) RRI values can independently predict renal failure. The recent claim that systemic (pulse pressure) rather than renal hemodynamic determinants sustain this predictive role of RRI, does not significantly reduce this predictive role of RRI. (c) Doppler ultrasound allows diagnosis and grading of renal stenosis in both fibromuscolar dysplastic and atherosclerotic diseases. Moreover, by RRI assay Doppler ultrasound can indirectly measure the hemodynamic impact of renal artery stenosis on the homolateral kidney, by virtue of the stenosis-related decrease in pulse pressure. However, in elderly subjects with atherosclerotic renal artery stenosis coexisting renal diseases can independently increase RRI by the augmentation in renal vascular stiffness and tubulo-interstitial pressure and hidden changes due to renal artery stenosis.

The effects of vitamin K supplementation and vitamin K antagonists on progression of vascular calcification: ongoing randomized controlled trials.

BackgroundThe extent and the progression of vascular calcification (VC) are independent predictors of cardiovascular risk in the haemodialysis population. Vitamin K is essential for the activation of matrix gla protein (MGP), a powerful inhibitor of tissue calcification. Functional vitamin K deficiency may contribute to the high VC burden in haemodialysis patients. In addition, haemodialysis patients are frequently treated with vitamin K antagonists, mainly to prevent stroke in atrial fibrillation, potentially compounding the cardiovascular risk in these already vulnerable patients. New oral anticoagulants (NOACs) are valuable alternatives to vitamin K antagonists in the general population, but their use in dialysis has been encumbered by substantial renal clearance. However, a recent pharmacokinetic study provided information on how to use rivaroxaban in haemodialysis patients.MethodsWe conduct a randomized, prospective, multicentre, open-label interventional clinical trial that will include 117 chronic haemodialysis patients with non-valvular atrial fibrillation, treated with or candidates for treatment with vitamin K antagonists. Patients will be randomized to a vitamin K antagonist titrated weekly to an international normalized ratio between 2 and 3, a daily dose of rivaroxaban of 10 mg, or a daily dose of rivaroxaban 10 mg with a thrice weekly supplement of 2000 µg vitamin K2. Cardiac computed tomography, pulse wave velocity (PWV) measurements and MGP sampling will be performed at baseline, 6 months, 12 months and 18 months. Primary endpoints include progression of coronary artery and thoracic aorta calcification and changes in PWV. Secondary endpoints are progression of aortic and mitral valve calcification, all-cause mortality, major adverse cardiovascular events, stroke and bleeding. The ClinicalTrials.gov database was searched to retrieve related trials.ResultsSeven trials, three of which are performed in the haemodialysis population, evaluate whether pharmacological doses of vitamin K1 or K2 retard progression of VC. Five studies compare the effect of warfarin and NOACs on progression of VC, the present study being the only conducted in the dialysis population.ConclusionVitamin K deficiency may be a modifiable cardiovascular risk factor in the haemodialysis population. Conversely, vitamin K antagonists may aggravate VC burden in haemodialysis patients. Several ongoing trials may provide an answer to these questions in the near future.

Markers of arterial stiffness in peripheral arterial disease.

Increased arterial stiffness results from reduced elasticity of the arterial wall and is an independent predictor for cardiovascular risk. The gold standard for assessment of arterial stiffness is the carotid-femoral pulse wave velocity. Other parameters such as central aortic pulse pressure and aortic augmentation index are indirect, surrogate markers of arterial stiffness, but provide additional information on the characteristics of wave reflection. Peripheral arterial disease (PAD) is characterised by its association with systolic hypertension, increased arterial stiffness, disturbed wave reflexion and prognosis depending on ankle-brachial pressure index. This review summarises the physiology of pulse wave propagation and reflection and its changes due to aging and atherosclerosis. We discuss different non-invasive assessment techniques and highlight the importance of the understanding of arterial pulse wave analysis for each vascular specialist and primary care physician alike in the context of PAD.

LDL electronegativity index: a potential novel index for predicting cardiovascular disease

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(–)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(–), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk.

Cocoa, Glucose Tolerance, and Insulin Signaling: Cardiometabolic Protection

Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring β-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases.

Peritoneal delivery of sodium pyrophosphate blocks the progression of pre-existing vascular calcification in uremic apolipoprotein-E knockout mice.

Chronic kidney disease (CKD) is generally associated with disturbances of mineral and bone metabolism. They contribute to the development of vascular calcification (VC), a strong, independent predictor of cardiovascular risk. Pyrophosphate (PPi), an endogenous inhibitor of hydroxyapatite formation, has been shown to slow the progression of VC in uremic animals. Since in patients with CKD treatment is usually initiated for already existing calcifications, we aimed to compare the efficacy of PPi therapy with that of the phosphate binder sevelamer, using a uremic apolipoprotein-E knockout mouse model with advanced VCs. After CKD creation or sham surgery, 12-week-old female mice were randomized to one sham group and four CKD groups (n=18-19/group). Treatment was initiated 8weeks after left nephrectomy allowing prior VC development. Uremic groups received either intraperitoneal PPi (high dose, 1.65mg/kg or low dose, 0.33mg/kg per day), oral sevelamer (3% in diet), or placebo treatment for 8weeks. Both intima and media calcifications worsened with time in placebo-treated CKD mice, based on both quantitative image analysis and biochemical measurements. Progression of calcification between 8 and 16weeks was entirely halted by PPi treatment, as it was by sevelamer treatment. PPi did not induce consistent bone histomorphometry changes. Finally, the beneficial vascular action of PPi probably involved mechanisms different from that of sevelamer. Further studies are needed to gain more precise insight into underlying mechanisms and to see whether PPi administration may also be useful in patients with CKD and VC.

The role of plasma triglyceride/high-density lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease.

BackgroundCardiovascular disease (CVD) risk is substantially increased in subjects with chronic kidney disease (CKD). The Triglycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C) ratio is an indirect measure of insulin resistance and an independent predictor of cardiovascular risk. No study to date has been performed to evaluate whether the TG/HDL-C ratio predicts CVD risk in patients with CKD.MethodsA total of 197 patients (age 53 ± 12 years) with CKD Stages 1 to 5, were enrolled in this longitudinal, observational, retrospective study. TG/HDL-C ratio, HOMA-IR indexes, serum asymmetric dimethyl arginine (ADMA), high sensitivity C-reactive protein (CRP), parathyroid hormone (PTH), calcium, phosphorous, estimated glomerular filtration rate (eGFR), and albumin levels were measured. Flow mediated vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasonography.ResultsA total of 11 cardiovascular (CV) deaths and 43 nonfatal CV events were registered in a mean follow-up period of 30 (range 9 to 35) months. Subjects with TG/HDL-C ratios above the median values (>3.29) had significantly higher plasma ADMA, PTH, and phosphorous levels (p = 0.04, p = 0.02, p = 0.01 respectively) and lower eGFR and FMD values (p = 0.03, p < 0.001 respectively). The TG/HDL-C ratio was an independent determinant of FMD (β = −0.25 p = 0.02) along with TG, HDL-C, hsCRP, serum albumin, phosphate levels, systolic blood pressure, PTH, eGFR and the presence of diabetes mellitus. The TG/HDL-C ratio was also a significant independent determinant of cardiovascular outcomes [HR: 1.36 (1.11-1.67) (p = 0.003)] along with plasma ADMA levels [HR: 1.31 (1.13-1.52) (p < 0.001)] and a history of diabetes mellitus [HR: 4.82 (2.80-8.37) (p < 0.001)].ConclusionThis study demonstrates that the elevated TG/HDL-C ratio predicts poor CVD outcome in subjects with CKD. Being a simple, inexpensive, and reproducible marker of CVD risk, the TG/HDL-C ratio may emerge as a novel and reliable indicator among the many well-established markers of CVD risk in CKD.Systematic review registrationClinical trial registration number and date: NCT02113462 / 10-04-2014.

Impacts of Comorbidities on the Association between Arterial Stiffness and Obstructive Sleep Apnea in the Elderly

Background: Although the impact of obstructive sleep apnea (OSA) on cardiovascular risk is reasonably well established in middle-aged patients, the debate persists as to whether OSA also increases this risk in the elderly. Arterial stiffness has been used as an early independent predictor of cardiovascular risk. Study Objectives: We sought to determine whether OSA has significant effects on the arterial stiffness in the elderly population and evaluate the impact of comorbidities on the association between arterial stiffness and OSA. Methods: We performed a cross-sectional study in a university hospital. Elderly participants (≥60 years) were invited to participate in our study between November 2010 and January 2013. OSA was diagnosed using gold standard polysomnography and arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI) and central systolic and diastolic blood pressure (cSBP and cDBP). The high-sensitivity C-reactive protein (hs-CRP) level was also measured. Results: We found no significant association between the severity of OSA and the arterial stiffness-related parameters cSBP, cDBP, baPWV, CAVI and hs-CRP. However, in patients with no comorbid medical conditions or use of medications (n = 101), we showed a modest association between OSA and arterial stiffness-related parameters and hs-CRP. Conclusion: We conclude that OSA is associated with increased arterial stiffness in an otherwise healthy elderly population, although the association was obviated by comorbidities and medications perhaps due to ceiling effects.

Noninvasive Assessment of Carotid Pulse Pressure Values: An Accelerometric-Based Approach.

Central pulse pressure (cPP) is increasingly investigated as possible independent predictor of cardiovascular risk and carotid pulse pressure (carPP) can be used as a surrogate of cPP. Despite its importance, carPP measurement remains challenging in clinical practice. The aim of this study was to introduce a new easier-to-use method for noninvasive carPP evaluation based on the use of a MEMS accelerometer. carPP values (carPP(acc)) were obtained in 22 subjects (10 males, 47 ±17 years, hypertension: 50%) postprocessing and double integrating the accelerometric signals. carPP(acc) measurements were compared with tonometric assessments (carPP(ton)), and ultrasound-derived measurements (carPP(us)). Moreover, accelerometric carotid pressure waveforms (P(acc)) were contrasted in terms of shape to those obtained by tonometry (P(ton)) and ultrasound images elaboration (P(US)), calculating the root mean square error (RMSE(ton), RMSE(US)) and the regression coefficients (r(ton) and r(US)). Moreover, both the repeatability and reproducibility analyses were performed. carPP(acc) values (45.9 ±10.6 mmHg) were significantly correlated with carPP(ton) (47.5 ±11.3 mmHg) and carPP(US) (43.3 ±8.4 mmHg) assessments (R = 0.94, p < 0.0001 and R = 0.80, p < 0.0001, respectively). The validity of the accelerometric approach was confirmed by morphological parameters ( RMSE(ton) = 5 ±1.95 mmHg, RMSE(US) = 5.5 ±2.3 mmHg, r(ton) = 0.94 ±0.04, r(US) = 0.93 ±0.04). Coefficient of variation (CV) was equal to 6.2% for the repeatability analysis, while CV values for interoperator and intersession reproducibilities were 8.9% and 9.4%, respectively. The proposed approach, providing an easier and more available measurement, could represent a valid alternative to existing and used technique for carPP assessment.

Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a&amp;nbsp;randomized controlled trial

BackgroundThere is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease.MethodsStable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec.ResultsTotal cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (−0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (−2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed.ConclusionThere was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown.

Glycated hemoglobin and its spinoffs: Cardiovascular disease markers or risk factors?

Atherosclerosis is a major complication of diabetes, increasing the risk of cardiovascular related morbidities and mortalities. The hallmark of diabetes is hyperglycemia which duration is best predicted by elevated glycated haemoglobin A1C (HbA1C) levels. Diabetic complications are usually attributed to oxidative stress associated with glycation of major structural and functional proteins. This non-enzymatic glycation of long lived proteins such as collagen, albumin, fibrinogen, liver enzymes and globulins result in the formation of early and advanced glycation end products (AGEs) associated with the production of myriads of free radicles and oxidants that have detrimental effects leading to diabetic complications. AGEs have been extensively discussed in the literature as etiological factors in the advancement of atherogenic events. Mechanisms described include the effects of glycation on protein structure and function that lead to defective receptor binding, impairment of immune system and enzyme function and alteration of basement membrane structural integrity. Hemoglobin (Hb) is a major circulating protein susceptible to glycation. Glycated Hb, namely HbA1C is used as a useful tool in the diagnosis of diabetes progression. Many studies have shown strong positive associations between elevated HbA1C levels and existing cardiovascular disease and major risk factors. Also, several studies presented HbA1C as an independent predictor of cardiovascular risk. In spite of extensive reports on positive associations, limited evidence is available considering the role of glycated Hb in the etiology of atherosclerosis. This editorial highlights potential mechanisms by which glycated hemoglobin may contribute, as a causative factor, to the progression of atherosclerosis in diabetics.

C-reactive protein as an additional marker for increased risk of cardiovascular disease in patients of hypothyroidism

Background: Prevalence of hypothyroidism and its subsequent cardiometabolic complications is on exponential rise. CRP is raised in hypothyroid patients long before other metabolic derangements of hypothyroidism take place and may be a common Patho physiological factor tying together various components of cardiometabolic dysfunction. Present study was aimed at evaluating the role of CRP as an additional cardiovascular risk marker in hypothyroid patients. Methods: 46 diagnosed hypothyroid patients and 46 age and sex matched healthy controls were included in this study. Participants were evaluated based on detailed history, clinical examination and laboratory investigations. Blood samples were collected after overnight fast. Serum T 3 , T 4 , TSH, Total Cholesterol (TC), Triglycerides (TG), HDL Cholesterol (HDL-C), VLDL Cholesterol (VLDL-C), LDL Cholesterol (LDL-C) and CRP were estimated. Results were analyzed by unpaired t-test, P-value was determined & Correlation coefficient was calculated amongst various parameters. Results: Statistically significant increased levels of serum TSH, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, VLDL cholesterol and CRP in hypothyroid patients as compared with control were observed. We found decreased levels of serum T 3 and T 4 in hypothyroid patients as compared with control. Conclusions: An atherogenic lipid profile along with inflammation in patients with hypothyroidism predispose them to cardiovascular disease. Study suggests CRP; a simple, sensitive & independent cardiovascular risk predictor in hypothyroid patients with a potential to reveal hidden burden of metabolic dysfunction and offers a hope that, cardiovascular event can be well prevented with appropriate interventions.

Arterial stiffness is inversely associated with a better running record in a full course marathon race.

[Purpose]Arterial stiffness is an independent predictor of cardiovascular risk and may contribute to reduced running capacity in humans. This study investigated the relationship between course record and arterial stiffness in marathoners who participated in the Seoul International Marathon in 2012.[Methods]A total of 30 amateur marathoners (Males n = 28, Females n = 2, mean age = 51.6 ± 8.3 years) were assessed before and after the marathon race. Brachial-ankle pulse wave velocity (ba-PWV) was assessed by VP-1000 plus (Omron Healthcare Co., Ltd., Kyoto, Japan) before and immediately after the marathon race. Pearson's correlation coefficient was used to determine the relationship between race record and ba-PWV. In addition, Wilcoxon signed rank test was used to determine the difference in ba-PWV between before and after the race.[Results]There was no significant change in the ba-PWV of marathoners before and after the race (1271.1 ± 185 vs. 1268.8 ± 200 cm/s, P=0.579). Both the full course record (Pearson's correlation coefficient = 0.416, P = 0.022) and the record of half line (Pearson's correlation coefficient = 0.482, P = 0.007) were positively related with the difference in ba-PWV, suggesting that reduced arterial stiffness is associated with a better running record in the marathon.[Conclusion]These results may suggest that good vascular function contributes to a better running record in the marathon race.

Changes in High-sensitivity C-reactive Protein Levels after Laparoscopic Gastric Stapling Procedures versus Laparoscopic Gastric Banding

Obesity, hypertension, diabetes, and hyperlipidemia are risk factors for the development of coronary artery disease. High-sensitivity C-reactive protein (hs-CRP) is an inflammatory biomarker that has been shown to be an independent predictor for cardiovascular risk. The aim of the current study was to examine the changes in cardiovascular risk profile in morbidly obese patients who underwent laparoscopic gastric stapling procedures (bypass and sleeve) compared with laparoscopic gastric banding. Levels of hs-CRP were measured preoperatively and at 12 to 24 months postoperatively. Based on hs-CRP levels, cardiovascular risk was categorized as low (less than 1 mg/L), moderate (1 to 3 mg/L), or high (greater than 3 mg/L). A total of 52 patients underwent gastric stapling procedures and 49 underwent gastric banding and both had preoperative and postoperative hs-CRP levels measured. There were no significant differences in age, gender, or preoperative body mass index (BMI) between groups. At baseline, 48.0 per cent of patients undergoing gastric stapling and 38.8 per cent of patients undergoing gastric banding had moderate or high cardiovascular risk. BMI at 24 months was significantly lower in the gastric stapling compared with the gastric banding group (30.4 ± 5.4 vs 36.1 ± 5.5 kg/m(2), respectively, P < 0.01). Of the patients with elevated cardiovascular risk, 64.0 per cent of gastric stapling versus 57.8 per cent of gastric banding patients had a reduction in risk category at 12 to 24 months follow-up, whereas 1.9 per cent of patients undergoing gastric stapling versus 4.1 per cent of patients undergoing gastric banding had an increase in risk category. The mean reduction in hs-CRP level for patients with elevated cardiovascular risk was greater for gastric stapling compared with gastric banding procedures (-1.10 ± 0.94 mg/L vs -0.67 ± 0.82 mg/L, respectively, P < 0.05). Cardiovascular risk improved in the majority of patients after bariatric surgery, but a more pronounced improvement occurred in patients who underwent gastric stapling procedures.

Evaluation of a Novel Brachial Cuff-Based Oscillometric Method for Estimating Central Systolic Pressure in Hemodialysis Patients

Background/Aims: Elevated wave reflections and arterial stiffness, as well as ambulatory blood pressure (BP) are independent predictors of cardiovascular risk in end-stage-renal-disease. This study is the first to evaluate in hemodialysis patients the validity of a new ambulatory oscillometric device (Mobil-O-Graph, IEM, Germany), which estimates aortic BP, augmentation index (AIx) and pulse wave velocity (PWV). Methods: Aortic SBP (aSBP), heart rate-adjusted AIx (AIx(75)) and PWV measured with Mobil-O-Graph were compared with the values from the most widely used tonometric device (Sphygmocor, ArtCor, Australia) in 73 hemodialysis patients. Measurements were made in a randomized order after 10 min of rest in the supine position at least 30 min before a dialysis session. Brachial BP (mercury sphygmomanometer) was used for the calibration of Sphygmocor's waveform. Results: Sphygmocor-derived aSBP and AIx(75) did not differ from the relevant Mobil-O-Graph measurements (aSBP: 136.3 ± 19.6 vs. 133.5 ± 19.3 mm Hg, p = 0.068; AIx(75): 28.4 ± 9.3 vs. 30.0 ± 11.8%, p = 0.229). The small difference in aSBP is perhaps explained by a relevant difference in brachial SBP used for calibration (146.9 ± 20.4 vs. 145.2 ± 19.9 mm Hg, p = 0.341). Sphygmocor PWV was higher than Mobil-O-Graph PWV (10.3 ± 3.4 vs. 9.5 ± 2.1 m/s, p < 0.01). All 3 parameters estimated by Mobil-O-Graph showed highly significant (p < 0.001) correlations with the relevant measurements of Sphygmocor (aSBP, r = 0.770; AIx(75), r = 0.400; PWV, r = 0.739). The Bland-Altman Plots for aSBP and AIx(75) showed acceptable agreement between the two devices and no evidence of systemic bias for PWV. Conclusion: As in other populations, acceptable agreement between Mobil-O-Graph and Sphygmocor was evident for aSBP and AIx(75) in hemodialysis patients; PWV was slightly underestimated by Mobil-O-Graph.

Glucagon-like peptide-1 as a key regulator of lipid and lipoprotein metabolism in fasting and postprandial states.

Insulin resistance and the metabolic syndrome are associated with fasting and postprandial dyslipidemia. This involves the hepatic and intestinal overproduction of very low density lipoproteins (VLDL) and chylomicron particles, respectively, which give rise to atherogenic remnants upon lipolysis in the circulation. Recently, the insulin secretagogue glucagon-like peptide-1 (GLP-1) has received attention not only as an anti-diabetic therapy for regulating glycaemia, but also as a regulator of lipid and lipoprotein metabolism. In fact, agents that raise endogenous bioactive levels of GLP-1 (dipeptidyl peptidase 4 inhibitors) and agents that directly stimulate GLP-1 receptors (GLP-1 receptor agonists) have been assessed in both preclinical and clinical trials for their ability to modulate plasma lipid parameters. Here we describe current evidence supporting a role for GLP-1 in preventing elevated intestinal chylomicron output and postprandial hypertriglyceridemia--an independent predictor of cardiovascular risk. Furthermore, we examine a role for GLP-1 in regulating fasting hepatic VLDL production and hindering the development of a potentially devastating comorbidity, hepatic steatosis. Possible mechanisms of action of GLP-1 are discussed including a reduction in intestinal absorption of dietary lipid and enhanced hepatic fatty acid oxidation or autophagy. Finally, we discuss the current controversy over whether these effects could occur via direct receptor stimulation or alternative, indirect pathways. We conclude that GLP- 1-based therapies appear promising in the management of diabetic dyslipidemia, and further studies are warranted to elucidate their mechanisms of action in both the intestine and liver.