Positive Association of Leptin and Artery Calcification of Lower Extremity in Patients With Type 2 Diabetes Mellitus: A Pilot Study.

Objective: We aimed to explore the role and possible mechanism of leptin in lower-extremity artery calcification in patients with type 2 diabetes mellitus (T2DM). Methods: We recruited 59 male patients with T2DM and 39 non-diabetic male participants. All participants underwent computed tomography scan of lower-extremity arteries. The calcification scores (CSs) were analyzed by standardized software. Plasma leptin level was determined by radioimmunoassay kits. Human vascular smooth muscle cells (VSMCs) calcification model was established by beta-glycerophosphate and calcium chlorideinduction. Calcium deposition and mineralization were measured by the o-cresolphthalein complexone method and Alizarin Red staining. The mRNA expression of bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and osteopontin (OPN) was determined by quantitative RT-PCR. The protein levels of BMP2, Runx2, α-smooth muscle actin (α-SMA) and (p)-Akt was determined by Western-blot analysis, and α-SMA was also measured by immunofluorescence analysis. Results: Compared with controls, patients with T2DM showed higher median calcification score in lower-extremity artery [286.50 (IQR 83.41, 1082.00) vs 68.66 (3.41, 141.30), p<0.01]. Plasma leptin level was higher in patients with calcification score ≥300 than ≥100 (252.67 ± 98.57 vs 189.38 ± 44.19 pg/ml, p<0.05). Compared with calcification medium, intracellular calcium content was significantly increased in VSMCs treated by leptin (200, 400 and 800 ng/ml) combined with calcification medium [11.99 ± 3.63, 15.18 ± 4.55, and 24.14 ± 5.85 mg/ml, respectively, vs 7.27 ± 1.54 mg/ml, all p<0.01]. Compared with calcification medium, Alizarin Red staining showed calcium disposition was more obvious, and the mRNA level of BMP2, Runx2 and OCN was significantly increased, and immunofluorescence and Western blot analysis showed that the expression of α-SMA was downregulated in VSMCs treated by leptin (400 ng/ml) combined with calcification medium, respectively. Compared with calcification medium, the protein level of BMP2 and Runx2 was upregulated in VSMCs treated by leptin (400 ng/ml) combined with calcification medium. Moreover, blocking PI3K/Akt signaling pathway can decrease the protein expression of BMP2 and Runx2 in VSMCs treated by leptin (400 ng/ml) combined with calcification medium. Conclusions: Leptin promoted lower-extremity artery calcification of T2DM by upregulating the expression of BMP2 and Runx2, and regulating phenotypic switch of VSMCs via PI3K/Akt signaling pathway.

Exploring biomarkers associated with deteriorating vascular health using a targeted proteomics chip: The SABPA study.

ABSTRACT: In this observational study, by the use of a multiplex proteomic platform, we aimed to explore associations between 92 targeted proteins involved in cardiovascular disease and/or inflammation, and phenotypes of deteriorating vascular health, with regards to ethnicity.Proteomic profiling (92 proteins) was carried out in 362 participants from the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study of black and white African school teachers (mean age 44.7 ±â€Š9.9 years, 51.9% women, 44.5% Black Africans, 9.9% with known cardiovascular disease). Three proteins with <15% of samples below detectable limits were excluded from analyses. Associations between multiple proteins and prevalence of hypertension as well as vascular health [Carotid intima-media thickness (cIMT) and pulse wave velocity (PWV)] measures were explored using Bonferroni-corrected regression models.Bonferroni-corrected significant associations between 89 proteins and vascular health markers were further adjusted for clinically relevant co-variates. Hypertension was associated with growth differentiation factor 15 (GDF-15) and C-X-C motif chemokine 16 (CXCL16). cIMT was associated with carboxypeptidase A1 (CPA1), C-C motif chemokine 15 (CCL15), chitinase-3-like protein 1 (CHI3L1), scavenger receptor cysteine-rich type 1 protein M130 (CD163) and osteoprotegerin, whereas PWV was associated with GDF15, E-selectin, CPA1, fatty acid-binding protein 4 (FABP4), CXCL16, carboxypeptidase B (CPB1), and tissue-type plasminogen activator. Upon entering ethnicity into the models, the associations between PWV and CPA1, CPB1, GDF-15, FABP4, CXCL16, and between cIMT and CCL-15, remained significant.Using a multiplex proteomic approach, we linked phenotypes of vascular health with several proteins. Novel associations were found between hypertension, PWV or cIMT and proteins linked to inflammatory response, chemotaxis, coagulation or proteolysis. Further, we could reveal whether the associations were ethnicity-dependent or not.

The potential value of Copeptin and Pentraxin3 for evaluating the severity of coronary stenosis in patients with coronary artery disease.

INTRODUCTION: Coronary artery disease (CAD) is an ischemic heart disease due to the narrowing of the coronary arteries resulting from atherosclerosis. Blood biomarkers have been well utilized for the diagnosis and prognosis of CAD. However, the value of biomarkers for evaluating coronary atherosclerosis remains to be clarified. This clinical investigation aimed to explore the potential value of biomarkers for evaluating the severity of coronary stenosis in CAD patients. METHODS: The extent of coronary atherosclerosis was accessed by the angiography-based quantitative measurement Gensini score (GS). Blood levels of Brain natriuretic peptide, Copeptin (CPP), Phosphodiesterase 9A, and Pentraxin3 (PTX3) were measured in 56 patients divided into three levels as low GS (n = 17), intermediate GS (n = 19) and high GS (n = 20) based on GS tertiles. RESULTS: We found that plasma concentrations of CPP and PTX3 were significantly elevated in patients with high GS compared with the low GS group. In addition, Pearson correlation analysis showed that CPP and PTX3 were positively correlated with the GS. Furthermore, Receiver operating characteristics analysis demonstrated that both CPP and PTX3 exhibited discriminative capacities for evaluating the extent of coronary stenosis. CONCLUSIONS: Laboratory tests of CPP and PTX3 via non-invasive means may provide novel information for risk stratification and disease management in CAD patients before invasive angiographic approaches. This study opens the door for enormous opportunities to explore new biomarkers with better efficiency, sensitivity and specificity as alternative/additional methods for evaluating the severity of coronary atherosclerosis in CAD patients in future research.

Efficacy and Safety of Prasugrel by Stroke Subtype: A Sub-Analysis of the PRASTRO-I Randomized Controlled Trial.

AIMS: The efficacy of antiplatelet therapy may vary among different disease subtypes. Prasugrel is generally a more potent, consistent, and fast-acting platelet inhibitor than clopidogrel. This sub-analysis of the phase III comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO-I) trial aimed to assess the differences in efficacy of these treatments for each stroke subtype. METHODS: In the PRASTRO-I trial, a total of 3,753 patients with ischemic stroke were recruited from 224 centers throughout Japan and randomized (1:1) to prasugrel (3.75 mg/day) or clopidogrel (75 mg/day) for 96 weeks. For the sub-analysis, strokes were classified as large-artery atherosclerosis, small-artery occlusion (lacunar), stroke of other etiology, and stroke of undetermined etiology. The cumulative incidence of primary events (ischemic stroke, myocardial infarction, and death from other vascular cause) and hazard ratios (HRs) were calculated for each subgroup. RESULTS: For patients with large-artery atherosclerosis, the primary event incidence was 3.8% in the prasugrel group and 4.8% in the clopidogrel group (HR 0.79; 95% confidence interval [CI] 0.45-1.41). For patients with small-artery occlusion, the incidence was 3.3% in the prasugrel group and 3.9% in the clopidogrel group (HR 0.82; 95% CI 0.45-1.50). For patients with stroke of undetermined etiology, the incidence was 4.6% in the prasugrel group and 3.0% in the clopidogrel group (HR 1.56; 95% CI 0.90-2.72). The incidence of bleeding was similar across subtypes. CONCLUSIONS: Although statistical significance was not reached, the efficacy of prasugrel was potentially different between stroke subtypes, warranting further studies.

[What's new in CKD-MBD?] / CKD-MBD: Was gibt es Neues?

CKD-MBD (chronic kidney disease - mineral and bone disorder) describes a complex syndrome of renal osteodystrophy, mineral disturbances and cardiovascular disease in patients with chronic kidney disease. The present articles intends to provide an up-to-date summary of recent clinically important developments in the field of CKD-MBD. The article touches specifically phosphate management, secondary hyperparathyroidism, vitamin D, arteriosclerosis, renal bone disease, and SGLT2-inhibitors. The summary also comments on which grade of evidence novel aspects and innovative developments in CKD-BMD are based. The author concludes that nephrologists should strive after more high-quality, large-scale randomized-controlled interventional trials in order to optimize the evidence behind CKD-MBD therapy.

The Relationship between Serum Vitamin E Level and Risk Factors for Arteriosclerosis in Japanese Postmenopausal Women.

Since vitamin E is one of the most potent antioxidant and anti-inflammatory agents, vitamin E can play a role against arteriosclerosis through various actions. Then, we have studied the relationship between serum vitamin E status and risk factors for arteriosclerosis in Japanese postmenopausal women. One hundred and seven subjects (70.0±7.7 y) were evaluated for vitamin E status by measuring serum α- and γ-tocopherol (αT and γT) levels. The number of arteriosclerosis risk factors was defined by the existence of high blood pressure, hyperglycemia, and dyslipidemia. Median serum αT and γT concentrations were 24.32 and 2.79 µmol/L, respectively. In none of the subjects, serum αT level was below the cutoff value (<12 µmol/L) for vitamin E deficiency which causes fragile erythrocyte and hemolysis. While no significant differences were found in serum levels of αT and γT between the groups categorized by the number of arteriosclerosis risks, serum levels of αT adjusted by serum total cholesterol (TC) and triglyceride (TG) decreased with an increasing number of arteriosclerotic risk factors (p=0.074). Serum αT level adjusted by serum TC and TG was also a negative significant predictor for the number of arteriosclerosis risk factors controlled by covariates associated with arteriosclerosis. The present study described that serum vitamin E level was positively associated with a lower number of arteriosclerotic risks, and its role for preventing noncommunicable diseases was suggested.

Phenotype of haptoglobin and presence of subclinical vascular disease: Population study. / Fenotipo de la haptoglobina y presencia de enfermedad vascular subclínica: estudio poblacional.

INTRODUCTION AND OBJECTIVES: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. PATIENTS AND METHODS: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. RESULTS: Of the 1,256 participants included in the present analysis (mean age 61.6±6years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P<.0001) and arterial hypertension (39.2% vs. 32.2%, P=.012), and they more frequently received treatment with statins (31.5% vs 21.6%, P<.0001), and with antihypertensive agents (38.4% vs 30.8%, P=.006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P=.011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95%CI 1.01-1.70, P=.044). CONCLUSION: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status.

Association Between Systemic Inflammation, Carotid Arteriosclerosis, and Autonomic Dysfunction.

Systemic inflammation is associated with arteriosclerotic disease progression and worse stroke outcome in patients with carotid arteriosclerotic disease. We hypothesize that systemic inflammation is mediated by impaired carotid baroreceptor and chemoreceptor function induced by carotid arteriosclerosis rather than by the generalized inflammatory arteriosclerotic process.Heart rate variability (HRV), serum levels of inflammatory markers, demographic and life style factors, and concomitant diseases with potential impact on systemic inflammation were determined in 105 patients with asymptomatic carotid stenosis of varying degree. Multivariate linear regression analyses were performed to ascertain independent determinants of carotid stenosis severity, autonomic function, and inflammation.Systemic inflammation (C-reactive protein, beta = .255; P = .014), age (beta = .232; P < .008), and arterial hypertension (beta = .206; P = .032) were associated with carotid stenosis severity. Only carotid stenosis severity and not generalized arteriosclerotic disease, concomitant diseases (arterial hypertension, diabetes mellitus, dyslipidemia, hypothyroidism), life style factors (smoking, obesity), or age was associated with a reduction in vagal tone (HRV HF band power beta = - .193; P < 0.049). Systemic inflammation was related to a reduction in vagal tone (HRV HF band power, beta = - .214; P = .031), and not to generalized arteriosclerotic disease, concomitant diseases (arterial hypertension, diabetes mellitus, dyslipidemia), life style factors (smoking, obesity), and age.In conclusion, systemic inflammation is associated with carotid rather than with generalized arteriosclerotic disease. The association between systemic inflammation and carotid arteriosclerosis is mediated by a reduction in vagal tone which indicates a major role of carotid arteriosclerosis-mediated autonomic dysfunction in the pathogenesis of systemic inflammation in arteriosclerotic disease.

LDL aggregation susceptibility is higher in healthy South Asian compared with white Caucasian men.

BACKGROUND: South Asians are more prone to develop atherosclerotic cardiovascular disease (ASCVD) compared with white Caucasians, which is not fully explained by classical risk factors. We recently reported that the presence of aggregation-prone low-density lipoprotein (LDL) in the circulation is associated with increased ASCVD mortality. OBJECTIVE: We hypothesized that LDL of South Asians is more prone to aggregate, which may be explained by differences in their LDL lipid composition. METHODS: In this cross-sectional hypothesis-generating study, LDL was isolated from plasma of healthy South Asians (n = 12) and age- and BMI-matched white Caucasians (n = 12), and its aggregation susceptibility and lipid composition were analyzed. RESULTS: LDL from South Asians was markedly more prone to aggregate compared with white Caucasians. Among all measured lipids, sphingomyelin 24:0 and triacylglycerol 56:8 showed the highest positive correlation with LDL aggregation. In addition, LDL from South Asians was enriched in arachidonic acid containing phosphatidylcholine 38:4 and had less phosphatidylcholines and cholesteryl esters containing monounsaturated fatty acids. Interestingly, body fat percentage, which was higher in South Asians (+26%), positively correlated with LDL aggregation and highly positively correlated with triacylglycerol 56:8, sphingomyelin 24:0, and total sphingomyelin. CONCLUSIONS: LDL aggregation susceptibility is higher in healthy young South Asians compared with white Caucasians. This may be partly explained by the higher body fat percentage of South Asians, leading to sphingomyelin enrichment of LDL. We anticipate that the presence of sphingomyelin-rich, aggregation-prone LDL particles in young South Asians may increase LDL accumulation in the arterial wall and thereby contribute to their increased risk of developing ASCVD later in life.

Apolipoprotein E polymorphisms contribute to statin response in Chinese ASCVD patients with dyslipidemia.

BACKGROUND: Apolipoprotein E (ApoE) plays an important role in lipid metabolism and clearance. Statins are the most common drugs used to modulate the lipid profile in the clinic therapy; the associations between ApoE polymorphisms and statin response to lipids were inconsistent in previous studies among different ethnicities. Our study aimed to demonstrate the relationships among the statins response and the ApoE gene common polymorphisms and lifestyle risk factors in Chinese arteriosclerotic cardiovascular disease (ASCVD) patients with dyslipidemia. METHODS: A total of 1002 dyslipidemia ASCVD patients were recruited in this study, including 311 patients with a history of type 2 diabetes mellitus (T2DM). These patients were all treated with drugs atorvastatin (10 mg/d) or rosuvastatin (5 mg/d) for at least 4 weeks and genotyped for ApoE e2/e3/e4 alleles, using Kompetitive Allele Specific PCR (KASP) and Sanger sequencing. The plasma lipids levels were determined before and after statins treatment. RESULTS: The results of ApoE genotyping with KASP method were consistent with the sequencing analysis. In the total 1002 patients, the E2 phenotypes (e2/e3, e2/e2) had significant lower low-density lipoprotein cholesterol (LDL-C) baseline levels than subjects with E3 (e3/e3, e2/e4) and E4 (e3/e4, e4/e4) phenotypes (P = 0.007, 0.005, respectively), and E2 phenotypes had the highest triglyceride (TG) baseline levels. To statins treatment, E2 phenotypes had a better response in TG, Total cholesterol (TC) and LDL-C reduction percentage compared with other phenotypes, and smoking/alcohol drinking status also had a significant influence on statins response of LDL-C lowering. No significant difference was found in the effects of lipids decreasing between atorvastatin and rosuvastatin drugs in all patients. CONCLUSIONS: We developed the KASP technique for the ApoE genotyping, and demonstrated ApoE polymorphisms interacted with smoking/drinking to influence the declining extent of TG, TC and LDL-C levels after statins therapy in Chinese dyslipidemia ASCVD patients. These discoveries developed our cognition with the genetic polymorphisms effects on statin response, which should be taken more seriously in smoking/drinking E4 amino acid isoform carriers.

Increased ApoB/ApoA1 ratio is associated with excess weight, body adiposity, and altered lipid profile in children / A razão ApoB/ApoA1 aumentada está associada ao excesso de peso, de adiposidade corporal e ao perfil lipídico alterado em crianças

Abstract Objective: To investigate ApoB/ApoA1 ratio and its association with cardiovascular risk factors in children. Methods: Cross-sectional study with 258 children aged 8 and 9 years old, enrolled in all urban schools in the city of Viçosa-MG. Anthropometric and body composition assessment, as well as biochemical profile of the children was performed. Socioeconomic variables and sedentary lifestyle were evaluated through a semi-structured questionnaire. Results: Many children had excess weight (35.2%), abdominal adiposity (10.5%), and body fat (15.6%), as well as increased ApoB/ApoA1 ratio (14.7%), total cholesterol (51.8%), and triglycerides (19.8%). Children with excess weight and total and central fat had a higher prevalence of having a higher ApoB/ApoA1 ratio, as well as those with atherogenic lipid profile (increased LDL-c and triglycerides and low HDL-c). A direct association was found between the number of cardiovascular risk factors and the ApoB/ApoA1 ratio (p = 0.001), regardless of age and income. Conclusion: The increased ApoB/ApoA1 ratio was associated with excess weight, body adiposity (total and central), and altered lipid profile in children. Children with a higher number of cardiovascular risk factors had higher ApoB/ApoA1 ratio, in both genders.

Resumo Objetivo: Investigar a razão ApoB/ApoA1 e sua relação com fatores de risco cardiovascular em crianças. Métodos: Estudo transversal com 258 crianças de 8 e 9 anos, matriculadas em todas as escolas urbanas de Viçosa-MG. Foi feita avaliação antropométrica, da composição corporal e bioquímica das crianças. As variáveis socioeconômicas e o sedentarismo foram avaliados por questionário semiestruturado. Resultados: Muitas crianças apresentaram excesso de peso (35,2%), de adiposidade abdominal (10,5%) e de gordura corporal (15,6%), bem como a razão ApoB/ApoA1 (14,7%), colesterol-total (51,8%) e triglicerídeos (19,8%) aumentados. Crianças com excesso de peso e de gordura total e central apresentaram maiores prevalências de maior razão ApoB/ApoA1, bem como as com perfil lipídico aterogênico (LDL-c e triglicerídeos aumentados e baixo HDL-c). Foi encontrada associação direta entre o número de fatores de risco cardiovascular e a razão ApoB/ApoA1 (p = 0,001), independente da idade e renda. Conclusão: A razão ApoB/ApoA1 aumentada esteve associada ao excesso de peso, de adiposidade corporal (total e central) e ao perfil lipídico alterado nas crianças. As crianças com maior número de fatores de risco cardiovascular apresentaram maior razão ApoB/ApoA1, em ambos os sexos.

Association of uric acid with stenosis of intracranial and extracranial arteries in elderly patients with cerebral infarction.

BACKGROUND: To determine whether uric acid (UA) and intracranial and extracranial atherosclerosis stenosis of elderly patients suffering from ischaemic stroke are inter-related. METHODS: Elderly patients with ischaemic stroke underwent computed tomography angiography (CTA) were enrolled between October 2015 and December 2017. We collected clinical assessment, image data, and laboratory tests, and divided patients into four groups: (1) intracranial stenosis atherosclerosis (ICAS) group, (2) combined intracranial and extracranial atherosclerosis stenosis (COAS) group, (3) extracranial carotid stenosis atherosclerosis (ECAS) group, and (4) non-cerebral stenosis atherosclerosis (NCAS) group. We used univariate and multiple logistic regression analyses to explore potential predictors. RESULTS: We included 408 patients in this study, then divided them into elder group (n = 196) and young- and middle-aged group (n = 212). In old stroke patients, 72 cases (36.73%) were classified as the ICAS group, 45 cases (22.96%) as the COAS group, 21 cases (10.71%) as the ECAS group, and 58 cases (29.59%) as the NCAS group. The level of UA was comparatively higher (p = 0.033) in ICAS than in NCAS. Compared with the group which had only one stenosis artery, UA was substantially increased in patients with more than one stenosis intracranial artery (p < 0.001). With a multivariable analysis, UA was an independent predictor for intracranial stenosis of elderly patients (OR = 1.003, p = 0.042), but the relationship between extracranial artery stenosis and uric acid was negative. CONCLUSIONS: Hyperuricaemia is a risk factor of intracranial artery stenosis rather than of ECAS in elderly patients with cerebral infarction.

Increased ApoB/ApoA1 ratio is associated with excess weight, body adiposity, and altered lipid profile in children.

OBJECTIVE: To investigate ApoB/ApoA1 ratio and its association with cardiovascular risk factors in children. METHODS: Cross-sectional study with 258 children aged 8 and 9 years old, enrolled in all urban schools in the city of Viçosa-MG. Anthropometric and body composition assessment, as well as biochemical profile of the children was performed. Socioeconomic variables and sedentary lifestyle were evaluated through a semi-structured questionnaire. RESULTS: Many children had excess weight (35.2%), abdominal adiposity (10.5%), and body fat (15.6%), as well as increased ApoB/ApoA1 ratio (14.7%), total cholesterol (51.8%), and triglycerides (19.8%). Children with excess weight and total and central fat had a higher prevalence of having a higher ApoB/ApoA1 ratio, as well as those with atherogenic lipid profile (increased LDL-c and triglycerides and low HDL-c). A direct association was found between the number of cardiovascular risk factors and the ApoB/ApoA1 ratio (p=0.001), regardless of age and income. CONCLUSION: The increased ApoB/ApoA1 ratio was associated with excess weight, body adiposity (total and central), and altered lipid profile in children. Children with a higher number of cardiovascular risk factors had higher ApoB/ApoA1 ratio, in both genders.

Correlations Between Serum Cholesterol and Vascular Lesions in Fabry Disease Patients.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder and shows globotriosylceramide (Gb3) accumulation in multiple organs, resulting from a deficiency of α-galactosidase. In patients with Fabry disease, cardiovascular disease occurs at an early age. Previous studies have shown that serum levels of high-density lipoprotein-cholesterol (HDL-C) increase in this disease, yet its clinical significance for cardiovascular disease remains unclear. Methods and Results: In order to determine why the serum HDL-cholesterol is high in various cardiovascular diseases of Fabry disease patients, we evaluated the serum lipid profiles, ocular vascular lesions, and levels of serum vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 in 69 patients with Fabry disease diagnosed by genetic examination. The serum HDL-C/total cholesterol (T-Chol) ratio was significantly high, especially in male patients (41.5±1.7%) regardless of body mass index. Ocular vascular lesions were more likely to occur in female patients with a high HDL-C/T-Chol ratio compared with most male patients. Female patients with a high HDL-C/T-Chol ratio also presented a high serum VEGF level, suggesting that vascular endothelium dysfunction and arteriosclerotic changes progress more severely than in patients with a normal HDL-C/T-Chol ratio. In most patients, enzyme replacement therapy improved serum Gb3 and lyso-Gb3 levels, but these Gb3 and lyso-Gb3 still remained higher than in healthy controls, which appears to result in continuous vascular arteriosclerotic changes. CONCLUSIONS: We concluded that increased low-density lipoprotein-cholesterol uptake to the vascular wall caused by endothelial dysfunction is likely to contribute to the high HDL-C/T-Chol ratio observed in Fabry disease patients.

Correlation between serum low-density lipoprotein cholesterol concentration and arterial wall stiffness.

BACKGROUND: Elevated serum low-density lipoprotein cholesterol (LDL-C) concentration is a risk factor for atherosclerosis, which involves remodelling of the arterial walls with their subsequent stiffening. AIM: We sought to evaluate the relationship between serum lipid levels and the elastic properties of the arterial wall. METHODS: The study group comprised 315 men and women aged 55.84 ± 9.44 years. Serum glucose and lipid concentrations were determited. All subjects underwent blood pressure (BP) measurement, transthoracic echocardiography, and assessment of vascular compliance of large (C1) and small arteries (C2) using the HDI/Pulse Wave™ CR-2000 Research CardioVascular Profiling System (Hypertension Diagnostics Inc., Eagan, MN, USA). The subjects were divided into three groups: group I - LDL-C < 2.6 mmol/L, group II - LDL-C ≥ 2.6 mmol/L and < 4.0 mmol/L, and group III - LDL-C ≥ 4.0 mmol/L. RESULTS: There were no intergroup differences with regard to smoking status (p = 0.56), serum glucose concentration (p = 0.13), body mass index (p = 0.96), systolic (p = 0.17) and diastolic BP (p = 0.29), or C1 (p = 0.09). However, C2 was higher in groups I and II than in group III (5.12 ± 2.57 vs. 5.18 ± 2.75 vs. 4.20 ± 1.58 mL/mmHg × 100, respectively, p < 0.01). Multivariate regression analysis negated the independent associations between C1 and serum lipid levels. In contrast, C2 was independently inversely associated with serum LDL-C concentration (r = -0.15, p < 0.01). CONCLUSIONS: Higher serum LDL-C concentration seems to contribute independently to stiffening of small arterial vasculature in otherwise healthy adults. Screening for dyslipidaemia in the general population and its prompt treatment are highly recom-mended.

Association of factor V activity with risk of venous thromboembolism and atherothrombotic cardiovascular events: A retrospective population-based cohort study.

INTRODUCTION: Factor V (FV) deficiency is a rare inherited coagulation disorder associated with bleeding tendency. As a result, it has been postulated that decreased FV activity may confer protection against venous thromboembolism and atherothrombotic cardiovascular events. MATERIALS AND METHODS: Using the electronic database of the largest health care provider in Israel, we identified all adult individuals who were tested for FV activity between January 2004 and June 2017. Subjects with liver cirrhosis or FV Leiden mutation were excluded. FV activity was classified into three predefined categories; FV activity >50%, FV activity 30-50%, and FV activity ≤30%. Patients were followed from January 2004 to June 2017 for new atherothrombotic cardiovascular events (composite of myocardial infarction, stroke, and TIA) and venous thromboembolism (VTE). RESULTS: Overall 2021 individuals were included; 83.2% had FV activity >50%, 9.6% FV activity 30-50%, and 7.2% had FV activity ≤30%. Compared to individuals with FV activity >50% the adjusted HR for atherothrombotic cardiovascular events was 1.10 (95% CI, 0.63-1.90) in those with FV activity 30-50%, and 0.95 (0.49-1.8) in those with FV activity ≤30%. None of the patients with FV activity 30-50% had VTE during follow-up; therefore those with FV activity ≤50% were classified into one group. VTE incidence was lower in those with FV activity ≤50% compared to those with FV >50% activity; adjusted HR = 0.28 (0.09-0.91). CONCLUSION: This study suggests that decreased FV activity might be associated with decreased incidence of VTE. No significant association appears to exist between FV activity and atherothrombotic cardiovascular events.

Circulating odd-chain saturated fatty acids were associated with arteriosclerosis among patients with diabetes, dyslipidemia, or hypertension in Sri Lanka but not Japan.

The differences in the morbidity and mortality of cardiovascular diseases between Sri Lankan and Japanese populations might be explained by the differences in their diet, especially fat. To test the hypothesis that the fatty acid (FA) compositions differ between Sri Lankan and Japanese populations and that high concentrations of n-3 polyunsaturated FAs and linoleic acid are associated with a low level of arteriosclerosis, the authors compared the circulating FA compositions between Sri Lankan and Japanese populations and examined the association of the circulating FA composition with arterial stiffness in each population. The study participants were patients with diabetes, dyslipidemia, or hypertension in Sri Lanka (n = 100) or Japan (n = 236). Serum FA compositions were measured by gas chromatography. Arterial stiffness was measured using the cardio-ankle vascular index (CAVI). Analysis of covariance was used to compare the FA compositions between the populations. Multiple regression was used to assess the association between each FA and CAVI levels. The concentrations of myristic, γ-linolenic, dihomo-γ-linolenic, and arachidonic acids were higher in the Sri Lankan patients than in the Japanese patients. In contrast, the concentrations of linoleic, α-linolenic, and eicosapentaenoic acids were higher in the Japanese patients than in the Sri Lankan patients. Although no associations of n-3 polyunsaturated FAs and linoleic acid with CAVI were observed in both patient populations, odd-chain saturated FAs (pentadecanoic and heptadecanoic acids) were significantly inversely associated with CAVI levels in the Sri Lankan (P for trend = .03) but not the Japanese patients. The odd-chain saturated FAs might be inversely associated with atherosclerosis in this Sri Lankan population.