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HPLC with spectrophotometric or mass spectrometric detection for quantifying very-long chain fatty acids in human plasma and its association with cardiac risk factors.
Shrestha, R, Chen, Z, Gao, Z, Chen, Y, Okada, E, Ukawa, S, Nakagawa, T, Nakamura, K, Tamakoshi, A, Chiba, H, et al
Annals of clinical biochemistry. 2021;(5):400-410
Abstract
BACKGROUND We developed and compared two liquid chromatography methods, one with UV/Visible spectrophotometric detection (HPLC) and the other with mass spectrometric detection (LC-MS), for quantifying very-long chain fatty acids (VLCFA) in human plasma. Association of VLCFA with various cardiovascular risk factors were evaluated. METHOD Fasting blood samples were collected from 541 human volunteers (242 men and 299 women; mean age ±SD, 58.9 ± 12.4 years), including 429 and 112 individuals with and without hypertriglyceridemia, respectively. Esterified VLCFA were saponified and derivatized with 2-nitrophenylhydrazine. Separation of VLCFA species was achieved with C4 Mightysil column (HPLC) and Ascentis Express Phenyl-Hexyl column (LC-MS) followed by spectrophotometric and selected-reaction monitoring mode of mass spectrometric detection, respectively. RESULTS The HPLC assay of VLCFA was precise with intra-assay imprecision of 2.5% to 6.9% and inter-assay imprecision of 3.2% to 9.5%. Moreover, there was an excellent correlation (r > 0.96) between HPLC and LC-MS methods. The 95 percentile reference intervals (RI; upper limit) of VLCFA were determined to be 41.3 µmol/L in healthy volunteers. Plasma VLCFA were significantly correlated with triglycerides (Spearman's ρ = 0.306, P < 0.001) and total cholesterol (Spearman's ρ = 0.251, P < 0.001). All species of VLCFA were significantly elevated in hypertriglyceridaemic individuals compared with control. CONCLUSION We established LC-based assays of VLCFA with either spectrophotometry or mass spectrometry as a detection system. Hypertriglyceridaemia is significantly associated with elevated concentration of each species of VLCFA.
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Safety and tolerability of high-intensity statin therapy in heart transplant patients receiving immunosuppression with tacrolimus.
Heeney, SA, Tjugum, SL, Corkish, ME, Hollis, IB
Clinical transplantation. 2019;(1):e13454
Abstract
BACKGROUND Following heart transplantation (HT), HMG CoA reductase inhibitors (statins) have been shown to reduce total and low-density lipoprotein (LDL) cholesterol, development of cardiac allograft vasculopathy (CAV), and mortality. Studies in HT patients have demonstrated the safety of low/moderate intensity statins; however, little data exist using high-intensity (HI) statins. The study aim was to evaluate the safety and efficacy of HI statins in HT recipients receiving tacrolimus. METHODS This single-center, retrospective analysis included adult HT recipients from January 1, 2005, to December 31, 2015, who received HI statin therapy during posttransplant follow-up. The primary outcome, tolerability, was defined as the absence of myalgias, hepatotoxicity, rhabdomyolysis, or HI statin dose reduction/discontinuation. The secondary end point was the mean reduction in total and LDL cholesterol. RESULTS Among the 24 patients included, one experienced myalgias and therapy discontinuation (4%; P > 0.99). No other HI statin dose reduction/discontinuation occurred, and no instances of rhabdomyolysis or hepatotoxicity were observed. The average reduction in total and LDL cholesterol after conversion to HI statin was 35 mg/dL (P = 0.02) and 19 mg/dL (P = 0.10), respectively. CONCLUSIONS High-intensity statin therapy appears safe and efficacious in HT recipients receiving tacrolimus and is a reasonable option for the treatment of refractory hyperlipidemia.
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Effects of Calcium-Channel Blocker Benidipine-Based Combination Therapy on Cardiac Events - Subanalysis of the COPE Trial.
Umemoto, S, Ogihara, T, Matsuzaki, M, Rakugi, H, Shimada, K, Kawana, M, Kario, K, Ohashi, Y, Saruta, T, ,
Circulation journal : official journal of the Japanese Circulation Society. 2018;(2):457-463
Abstract
BACKGROUND The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was conducted to compare the effects of regimens combining the dihydropyridine calcium-channel blocker benidipine with each of 3 secondary agent types (an angiotensin-receptor blocker (ARB), a β-blocker and a thiazide) in Japanese hypertensive outpatients who did not achieve target blood pressure (<140/90 mmHg) with benidipine 4 mg/day alone. The analysis included 3,293 patients (ARB, 1,110; β-blocker, 1,089; thiazide, 1,094) with a median follow-up of 3.61 years. The main results of the COPE trial demonstrated that the incidences of hard cardiovascular composite endpoints and fatal or non-fatal strokes were significantly higher in the benidipine/β-blocker group than in the benidipine/thiazide group.Methods and Results:We further evaluated the treatment effects on different cardiac events among the 3 benidipine-based regimens.We observed a total of 50 cardiac events, 4.2 per 1000 person-years. The incidences of total cardiac events and each cardiac event were similarly low among the 3 treatment groups. Unadjusted and multi-adjusted hazard ratios for total cardiac events showed no significant difference among the 3 treatment groups. CONCLUSIONS This subanalysis of the COPE trial demonstrated that blood pressure-lowering regimens combining benidipine with an ARB, β-blocker or thiazide diuretic were similarly effective for the prevention of cardiac events in Japanese hypertensive outpatients.
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Correlation among soluble receptors for advanced glycation end-products, soluble vascular adhesion protein-1/semicarbazide-sensitive amine oxidase (sVAP-1) and cardiometabolic risk markers in apparently healthy adolescents: a cross-sectional study.
Gurecká, R, Koborová, I, Csongová, M, Šebek, J, Šebeková, K
Glycoconjugate journal. 2016;(4):599-606
Abstract
In non-diabetics, low levels of soluble receptor for advanced glycations end products (sRAGE) associate with an increased risk of development of diabetes, cardiovascular afflictions, or death. The majority of studies in non-diabetics report an inverse relationship between measures of obesity, cardiometabolic risk factors and sRAGE and/or endogenous secretory RAGE (esRAGE) levels. To elucidate whether this inconsistency is related to the metabolically healthy obese phenotype, or a different impact of the risk factors in presence and absence of obesity, we analyzed data from 2206 apparently healthy adolescents (51 % girls) aged 15-to-19 years. The association of sRAGE levels with soluble vascular adhesion protein-1/semicarbazide sensitive amine oxidase (sVAP-1/SSAO) was also investigated. Centrally obese, including metabolically healthy, adolescents present significantly lower sRAGE and esRAGE, but not sVAP-1, levels in comparison with their lean counterparts. An increasing number of cardiometabolic risk factors did not associate with significant changes in sRAGE, esRAGE or sVAP-1 levels either in lean or in obese subjects. In multivariate analyses, WHtR, hsCRP, markers of glucose homeostasis, renal function, adiponectin, and sVAP-1 associated significantly with sRAGE and esRAGE. SVAP-1 correlated significantly with glycemia, adiponectin, hsCRP, and sRAGE. Thus, in adolescents, a decline in sRAGE and esRAGE precedes the development of metabolic syndrome. When combined, standard and non-standard cardiometabolic risk factors explain only minor proportion in a variability of sRAGE and esRAGE (8 %-11 %); or sVAP-1 (12 %-20 %). Elucidation of pathogenetic mechanisms underlying early decline in sRAGE and esRAGE levels in obese adolescents and their clinical impact with regard to future cardiometabolic health requires further studies.
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Obesity favors apolipoprotein E- and C-III-containing high density lipoprotein subfractions associated with risk of heart disease.
Talayero, B, Wang, L, Furtado, J, Carey, VJ, Bray, GA, Sacks, FM
Journal of lipid research. 2014;(10):2167-77
Abstract
Human HDLs have highly heterogeneous composition. Plasma concentrations of HDL with apoC-III and of apoE in HDL predict higher incidence of coronary heart disease (CHD). The concentrations of HDL-apoA-I containing apoE, apoC-III, or both and their distribution across HDL sizes are unknown. We studied 20 normal weight and 20 obese subjects matched by age, gender, and race. Plasma HDL was separated by sequential immunoaffinity chromatography (anti-apoA-I, anti-apoC-III, anti-apoE), followed by nondenaturing-gel electrophoresis. Mean HDL-cholesterol concentrations in normal weight and obese subjects were 65 and 50 mg/dl (P = 0.009), and total apoA-I concentrations were 119 and 118 mg/dl, respectively. HDL without apoE or apoC-III was the most prevalent HDL type representing 89% of apoA-I concentration in normal weight and 77% in obese (P = 0.01) individuals; HDL with apoE-only was 5% versus 8% (P = 0.1); HDL with apoC-III-only was 4% versus 10% (P = 0.009); and HDL with apoE and apoC-III was 1.5% versus 4.6% (P = 0.004). Concentrations of apoE and apoC-III in HDL were 1.5-2× higher in obese subjects (P ≤ 0.004). HDL with apoE or apoC-III occurred in all sizes among groups. Obese subjects had higher prevalence of HDL containing apoE or apoC-III, subfractions associated with CHD, whereas normal weight subjects had higher prevalence of HDL without apoE or apoC-III, subfractions with protective association against CHD.
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Inpatient cardiac rehabilitation and changes in self-reported health related quality of life--a pilot study.
Weberg, M, Hjermstad, MJ, Hilmarsen, CW, Oldervoll, L
Annals of physical and rehabilitation medicine. 2013;(5):342-55
Abstract
OBJECTIVE To assess changes in self-reported health related quality of life (HRQoL) among cardiac patients who participated in an inpatient rehabilitation programme. PATIENTS AND METHODS Medical Outcomes Study Short Form 36 (SF-36) and the MacNew Heart Disease Health-related Quality of Life Questionnaire (MacNew) was used to assess HRQoL at baseline (T1), after rehabilitation (T2) and 5 months after discharge (T3). The rehabilitation programme consisted of physical exercise, theoretical education, group discussions and individual consultations. Friedman's test with Wilcoxon post-hoc test was used to analyse changes between T1, T2 and T3. Effect size (ES) were calculated. RESULTS Eighty-nine participants were included (79% male) with mean age of 60.0 ± 8.6 years. All SF-36 and MacNew domains showed significant improvement from T1 to T2 (P < 0.05), and all except the SF-36 domain for emotional role with a moderate to large ES. At T3, change and ES are diminished in all domains, except for the physical and social domains of the MacNew. CONCLUSION These findings indicate an improvement in HRQoL over time among cardiac patients attending the rehabilitation programme, particularly so in the domains of physical role and physical function, vitality, bodily pain and emotional-, physical- and social-well-being, all which are important domains for maintaining an active life. Future randomised studies comparing inpatient- and outpatient-programmes with longer follow-up are necessary to ascertain if such improvements persist and if patients are able to change life-style in line with the stated goals of cardiac rehabilitation (CR).
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Diagnostic value of lung auscultation in an emergency room setting.
Leuppi, JD, Dieterle, T, Koch, G, Martina, B, Tamm, M, Perruchoud, AP, Wildeisen, I, Leimenstoll, BM
Swiss medical weekly. 2005;(35-36):520-4
Abstract
BACKGROUND In daily routine, physicians use history, physical examination and technology-based information such as laboratory tests and imaging studies to diagnose the patients' disease. We determined the diagnostic value of lung auscultation in patients admitted to the Medical emergency room with chest symptoms. METHODS Two-hundred-and forty-three consecutive patients (137 males), mean age 59.2 years were included. Internal Medicine registrars had to make a presumptive diagnosis, 1) after having taken the history and 2) after having auscultated the lungs. Thereafter, routine diagnostic procedures were performed. The estimated diagnosis was compared with the final diagnosis based on the written report to the Family Practitioner. RESULTS Two-hundred-eighty-seven diagnoses were made. Eighteen percent of patients suffered from left heart failure, 13% from unexplained chest pain, 10.5% from chest wall pain, and 10.5% from pneumonia. Forty-one percent of the diagnoses were already correct when based only on the patient's history. Lung auscultation improved the diagnostic yield only in 1% and worsened it in another 3%. By multiple logistic regression, normal lung auscultation (OR 0.12 [95CI% 0.053-0.29]) was the independent predictor for not having a lung or heart disease. However, elevation of B-type natiuretic peptide (BNP) (OR 1.16 per 100 pg/ml (95CI% 1.004-1.35), wheezing (OR 0.023 [0.002-0.33]) and pCO2 (OR 0.25 (0.10-0.621) were independent predictors for having a heart disease, whereas wheezing (OR 7.41 [3.26-16.83]) and CRP (OR 1.008 per 10 units [1.003-1.014]) were risk factors for having a lung disease. CONCLUSION In contrast to history taking, abnormal lung auscultation does not appear to contribute considerably to the final diagnosis in patients presenting with chest symptoms in an emergency room setting. However, normal lung auscultation is a valuable predictor for not having a lung or heart disease, whereas wheezing is a predictor for having a lung disease and not having a heart disease.
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Effects of a low-glycemic load diet on resting energy expenditure and heart disease risk factors during weight loss.
Pereira, MA, Swain, J, Goldfine, AB, Rifai, N, Ludwig, DS
JAMA. 2004;(20):2482-90
Abstract
CONTEXT Weight loss elicits physiological adaptations relating to energy intake and expenditure that antagonize ongoing weight loss. OBJECTIVE To test whether dietary composition affects the physiological adaptations to weight loss, as assessed by resting energy expenditure. DESIGN, STUDY, AND PARTICIPANTS A randomized parallel-design study of 39 overweight or obese young adults aged 18 to 40 years who received an energy-restricted diet, either low-glycemic load or low-fat. Participants were studied in the General Clinical Research Centers of the Brigham and Women's Hospital and the Children's Hospital, Boston, Mass, before and after 10% weight loss. The study was conducted from January 4, 2001, to May 6, 2003. MAIN OUTCOME MEASURES Resting energy expenditure measured in the fasting state by indirect calorimetry, body composition by dual-energy x-ray absorptiometry, cardiovascular disease risk factors, and self-reported hunger. RESULTS Resting energy expenditure decreased less with the low-glycemic load diet than with the low-fat diet, expressed in absolute terms (mean [SE], 96 [24] vs 176 [27] kcal/d; P = .04) or as a proportion (5.9% [1.5%] vs 10.6% [1.7%]; P = .05). Participants receiving the low-glycemic load diet reported less hunger than those receiving the low-fat diet (P = .04). Insulin resistance (P = .01), serum triglycerides (P = .01), C-reactive protein (P = .03), and blood pressure (P = .07 for both systolic and diastolic) improved more with the low-glycemic load diet. Changes in body composition (fat and lean mass) in both groups were very similar (P = .85 and P = .45, respectively). CONCLUSIONS Changes in dietary composition within prevailing norms can affect physiological adaptations that defend body weight. Reduction in glycemic load may aid in the prevention or treatment of obesity, cardiovascular disease, and diabetes mellitus.
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Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration.
De Hert, SG, Van der Linden, PJ, Cromheecke, S, Meeus, R, Nelis, A, Van Reeth, V, ten Broecke, PW, De Blier, IG, Stockman, BA, Rodrigus, IE
Anesthesiology. 2004;(2):299-310
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Abstract
BACKGROUND Experimental studies have related the cardioprotective effects of sevoflurane both to preconditioning properties and to beneficial effects during reperfusion. In clinical studies, the cardioprotective effects of volatile agents seem more important when administered throughout the procedure than when used only in the preconditioning period. The authors hypothesized that the cardioprotective effects of sevoflurane observed in patients undergoing coronary surgery with cardiopulmonary bypass are related to timing and duration of its administration. METHODS Elective coronary surgery patients were randomly assigned to four different anesthetic protocols (n = 50 each). In a first group, patients received a propofol based intravenous regimen (propofol group). In a second group, propofol was replaced by sevoflurane from sternotomy until the start of cardiopulmonary bypass (SEVO pre group). In a third group, propofol was replaced by sevoflurane after completion of the coronary anastomoses (SEVO post group). In a fourth group, propofol was administered until sternotomy and then replaced by sevoflurane for the remaining of the operation (SEVO all group). Postoperative concentrations of cardiac troponin I were followed during 48 h. Cardiac function was assessed perioperatively and during 24 h postoperatively. RESULTS Postoperative troponin I concentrations in the SEVO all group were lower than in the propofol group. Stroke volume decreased transiently after cardiopulmonary bypass in the propofol group but remained unchanged throughout in the SEVO all group. In the SEVO pre and SEVO post groups, stroke volume also decreased after cardiopulmonary bypass but returned earlier to baseline values than in the propofol group. Duration of stay in the intensive care unit was lower in the SEVO all group than in the propofol group. CONCLUSION In patients undergoing coronary artery surgery with cardiopulmonary bypass, the cardioprotective effects of sevoflurane were clinically most apparent when it was administered throughout the operation.
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Long-term, continuous treatment with both oral and transdermal nitrates increases cardiac events in healed myocardial infarction patients.
Kanamasa, K, Hayashi, T, Kimura, A, Ikeda, A, Ishikawa, K
Angiology. 2002;(4):399-408
Abstract
This study was performed to investigate the effects of continuous dosing of oral, transdermal (patch), and a combination of the two with nitrate treatments on cardiac events in patients with healed myocardial infarction. In total, 1,291 patients with healed myocardial infarction were assigned 2 groups: treatment with nitrates (n=713) or nontreatment (n=578). Nitrate treatment was subdivided into 3 groups: patch group (n=149), oral group (n=504), and combination group (n=60). The mean observation period was 17.4 +/- 21.1 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics were also compared among the 4 groups to determine any effects on outcome. Among the patients with patch, oral, and combination groups, cardiac events occurred 3.4%, 6.7%, 10.0%, respectively, whereas only 2.9% of the patients treated without nitrates had cardiac events. The incidence of cardiac events was significantly greater in patients with oral nitrates and combination groups compared to patients without nitrates (p<0.01, respectively). Continuous dosing of long-term treatment with both oral and transdermal nitrates increased cardiac events in healed myocardial infarction patients.