Ankle-brachial index and brachial-ankle pulse wave velocity are risk factors for ischemic stroke in patients with type 2 diabetes

The incidence of ischemic stroke in patients with diabetes is increasing. While brachial-ankle pulse wave velocity （BaPWV） and ankle-bra- chial index （ABI） are known to be associated with ischemic cardiovascular and cerebrovascular diseases, whether these measures predict the risk of ischemic cerebrovascular disease in diabetic patients remains unclear. 117 patients with type 2 diabetes were enrolled in this study. According to the results of head magnetic resonance imaging, the patients were divided into a diabetes-only group （n = 55） and a diabetes and ischemic stroke group （n = 62）. We then performed ABI and BaPWV examinations for all patients. Compared with the diabe- tes-only group, we found decreased ABI and increased BaPWV in the diabetes and ischemic stroke group. Multivariate logistic regression analyses revealed that BaPWV and ABI were risk factors for ischemic stroke in patients with type 2 diabetes. Our findings indicate that decreased ABI and increased BaPWV are objective indicators of increased risk of ischemic stroke in patients with type 2 diabetes.

Serum Calcium Level is Associated with Brachial-ankle Pulse Wave Velocity in Middle-aged and Elderly Chinese

Objective To study the relation between serum calcium level and elevated BaPWV in Chinese subjects. Methods The relation between serum calcium level and elevated BaPWV was studied in 9 615 subjects. The mean value of left and right BaPWV was analyzed. BaPWV was defined as high when it was31 752.5 cm/s （the upper quartile） either side. Results The BaPWV and its elevated percentage progressively increased across the quartiles of the serum calcium level （P〈0.05）. The prevalence of elevated BaPWV was significantly higher in subjects of the second, third and highest quartiles than in those of the lowest quartile （26.9%, 28.4%, and 33.2%vs 23.7%, P=0.0116, P=0.0004, and P〈0.0001）. Logistic regression analysis revealed that the risk of elevated BaPWV was 1.32- fold higher in subjects of the highest quartile than in those of the lowest quartile （OR=1.32, 95%CI：1.08-1.60）. Conclusion The elevated serum calcium level is related to an elevated BaPWV and a higher risk of arterial stiffness, independent of conventional risk factors, in middle-aged and elderly Chinese subjects.

Relationship between brachial-ankle pulse wave velocity and metabolic syndrome components in a Chinese population

The purpose of this study was to assess the relationship between arterial stiffness, as measured by brachial-ankle pulse wave velocity （baPWV）, and the presence of the metabolic syndrome （MS） in a Chinese population. A total of 4,445 subjects were enrolled. The prevalence of MS in for the general population, males and females, respectively. our study population was 21.7%, 17.2% and 25.6% With adjustments for age, gender, cigarette smoking, heart rate, total cholesterol, low-density lipoprotein （LDL） cholesterol, and the use of anti-hypertensive drug, the stepwise regression analysis showed that baPWV had a significant relationship with components of MS, including systolic blood pressure （P 〈 0.001）, diastolic blood pressure （P 〈 0.001）, glucose （P 〈 0.001）, highdensity lipoprotein （HDL） cholesterol （P = 0.04）, and triglycerides （P 〈 0.001）, but no relationship with waist circumference （P = 0.25）. With an increase in the number of the MS components, baPWV increased significantly both in women and men. This study indicated that the MS is indeed a risk factor for arterial stiffness. Monitoring of baPWV in patients with MS may help in identifying persons at high risk for cardiovascular disease.

Increased brachial-ankle pulse wave velocity is associated with impaired endothelial function in patients with coronary artery disease

Background Pulse wave velocity and flow-mediated vasodilation （FMD） are widely used as noninvasive modalities for evaluating atherosclerosis. However, it is not known whether pulse wave velocity is related to FMD in patients with coronary artery disease （CAD）. Therefore, the present study was designed to investigate the alteration in brachial-ankle pulse wave velocity （baPWV） and endothelial function in CAD patients. Methods Thirty-three patients with CAD and thirty control subjects were recruited for this study, baPWV was measured non-invasively using a VP 1000 automated PWV/ABI analyzer （PWV/ABI, Colin Co. Ltd., Komaki, Japan）. Endothelial function as reflected by FMD in the brachial artery was assessed with a high-resolution ultrasound device. Results baPWV was increased in CAD patients compared with control subjects [（1756.1±253.1） cm/s vs （1495.3±202.3） cm/s, P〈0.01]. FMD was significantly reduced in CAD patients compared with control subjects [（5.2±2.1） % vs （11.1±4.4） %, P〈0.01]. baPWV correlated with FMD （r =-0.68, P〈0.001）. The endothelium-independent vasodilation induced by sublingual nitroglycerin in the brachial artery was similar in the CAD group compared with the control group.Conclusions CAD is associated with increased baPWV and endothelial dysfunction. Increased baPWV parallels diminished endothelial function. Our data therefore suggest that baPWV can be used as a noninvasive surrogate index in clinical evaluation of endothelial function.

Reference values of brachial-ankle pulse wave velocity for Northern Chinese

Background Brachial-ankle pulse wave velocity （baPWV） is a reliable method for measuring arterial elasticity, but the absence of reference value for baPWV has limited its wide use. We conducted an epidemical study in north China to investigate the reference value of baPWV for Chinese people and its influential factors. Methods A total of 974 identified healthy subjects were recruited in this study. The values of baPWV were evaluated noninvasively with an automatic device. Results For healthy population, the mean value of baPWV was higher for male （P 〈0.001）. Multiple regression analysis demonstrated that both age and systolic blood pressure were positively associated with baPWV for male and female （P 〈0.001）. BaPWV value was higher in male than in female in younger group （〈50 years） but not in older group （P〈-0.001）. The upper limits of baPWV were 1394/1264 cm/s, 1435/1361 cm/s, 1552/1433 cm/s, 1597/1609 cm/s and 1798/1915 cm/s for healthy male/female at 10 years interval （age range 20-70 years）. Conclusions Aging is the most important reason of arterial stiffness, but the effect of age on baPWV augmentation is greater for healthy female than their male counterpart. The reference values of baPWV by sex and age are very useful for clinical and preventive medicine.

Can we early diagnose metabolic syndrome using brachial-ankle pulse wave velocity in community population？

Background The prevalence of metabolic syndrome （MetS） increased recently and there was still not a screening index to predict MetS.The aim of this study was to estimate whether brachial-ankle pulse wave velocity （baPVVV）,a novel marker for systemic arterial stiffness,could predict MetS in Chinese community population.Methods A total of 2 191 participants were recruited and underwent medical examination including 1 455 men and 756 women from June 2011 to January 2012.MetS was diagnosed according to the criteria of the International Diabetes Federation （IDF）.Multiple Logistic regressions were conducted to explore the risk factors of MetS.Receiver operating characteristic （ROC） curve was performed to estimate the ideal diagnostic cutoff point of baPWV to predict MetS.Results The mean age was （45.35±8.27） years old.In multiple Logistic regression analysis,the gender,baPWV and smoking status were risk factors to MetS after adjusting age,gender,baPWV,walk time and sleeping time.The prevalence of MetS was 17.48% in 30-year age population in Shanghai.There were significant differences （Х^2=96.46,P 〈0.05） between male and female participants on MetS prevalence.According to the ROC analyses,the ideal cutoff point of baPWV was 1 358.50 cm/s （AUC=60.20%） to predict MetS among male group and 1 350.00 cm/s （AUC=70.90%） among female group.Conclusion BaPWV may be considered as a screening marker to predict MetS in community Chinese population and the diagnostic value of 1 350.00 cm/s was more significant for the female group.

New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse wave velocity and albuminuria: a prospective cohort study

A new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)has recently been proposed.We aim to examine the associations of MAFLD,particularly its discordance from non-alcoholic fatty liver disease(NAFLD),with the progression of elevated brachial-ankle pulse wave velocity(baPWV)and albuminuria in a community-based study sample in Shanghai,China.After 4.3 years of follow-up,778 participants developed elevated baPWV and 499 developed albuminuria.In comparison with the non-MAFLD group,the multivariable adjusted odds ratio(OR)of MAFLD group for new-onset elevated baPWV was 1.25(95%confidence interval(CI)1.01–1.55)and 1.35(95%CI 1.07–1.70)for albuminuria.Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria(OR 1.77;95%CI 1.07–2.94).Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria.In conclusion,MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index,waist circumference,and hip circumference.Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria,supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

Relationship between the Plasma Fibulin-1 Levels,Pulse Wave Velocity,and Vascular Age in Asymptomatic Hyperuricemia

Fibulin-1(FBLN-1),an elastin-associated extracellular matrix protein,has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease(CVD).We aimed to investigate the relationship between fibulin-1 levels and the risk of CVD by evaluating vascular age derived from the Framingham Heart Study and brachial-ankle Pulse Wave Velocity(baPWV)in patients with asymptomatic hyperuricemia(AHU).In total,66 patients with AHU and 66 gender-and age-matched healthy individuals were enrolled.The plasma fibulin-1 levels were measured by immunochemistry.Patients with AHU presented significantly higher vascular age[median(interquartile range):54(22)vs.48(14)years,P=0.01]and baPWV[mean±SD:1373±223 vs.1291±177 cm/s,P=0.02]than the healthy subjects;however,no significant difference was observed in the plasma fibulin-1 level between the patients with AHU and healthy subjects[median(interquartile range):4018(3838)vs.3099(3405)ng/mL,P=0.31].A correlation between fibulin-1 levels and baPWV was observed only in patients with AHU(r=0.29,P=0.02);and there was also a suggestively statistically significant correlation between fibulin-1 levels and vascular age(r=0.22,P=0.08).However,these associations were rendered insignificant after adjustments for potential confounders.In healthy subjects,no correlation was observed between fibulin-1 levels and CVD risk.This study reveals that plasma fibulin-1 levels may reflect the CVD risk in patients with AHU,but the relationship is not robust.

A family history of diabetes is not associated with arterial stiffness in non-diabetic Japanese population

Prevalent diabetes is at high risk for cardiovascular diseases and has a high familial inheritance. However, little is known whether a non-diabetic subject with a family history of diabetes is at high risk for vascular damage or not. The purpose of this study was to evaluate the association between a family history of diabetes and arterial stiffness in adult non-diabetic Japanese population. We analyzed eligible 787 non-diabetic subjects (502 men and 285 women) aged 35-69 years who enrolled in the baseline survey of a cohort study in Tokushima Prefecture, Japan and who underwent a brachial-ankle pulse wave velocity (ba-PWV) measurement. Information on individual life-style characteristics including medical history and treatment for diseases and a first-degree family history of diabetes was obtained through a structured self-administered questionnaire. Analysis of covariance and logistic regression analyses were used to evaluate the association between a family history of diabetes and ba-PWV. We found no differences in age-and-systolic blood pressure-adjusted and multivariate-adjusted means of ba-PWVs between subjects of both sexes with and without a family history of diabetes. Logistic regression analyses including both sexes also revealed that subjects with a family history of diabetes showed no differences in age-and-systolic blood pressure-adjusted and multivariate-adjusted odds ratios for high ba-PWV compared to those without that trait. Our results suggest that a family history of diabetes itself is not associated with arterial stiffness in adult non-diabetic Japanese population.

Composition and Functional Capacity of Gut Microbes are Associated with Arterial Stiffness:A Prospective Study

Objective:Arterial stiffness is an important predictor of cardiovascular disease.Microbial diversity in the gut has been shown to be associated inversely with arterial stiffness in Caucasian populations.However,due to the different profiles of the gut microbiota among ethnicities,the relationship between gut-microbiota dysbiosis and the progression of arterial stiffness merits further investigation.This study aimed to investigate the association between the composition and functional capacity of the gut microbiota and the progression of arterial stiffness.Methods:“Shotgun”metagenomics sequencing were undertaken in 96 individuals from a hypertension-associated gut-microbiota study in the Kailuan cohort,who measured brachial-ankle pulse wave velocity(baPWV)and provided fecal samples between September 2014 and February 2015 at Kailuan General Hospital and 11 affiliated hospitals.The different composition and functional capacity of the gut microbiota were compared between individuals without arterial stiffness(normal arterial stiffness group,baPWV<1,400 cm/s,n=27)and participants with arterial stiffness(increased arterial stiffness group,baPWV≥1,400 cm/s,n=69)at baseline.These participants were followed up prospectively for a mean duration of 2.6 years,and 50 underwent a repeat baPWV measurement.Associations between the gut microbiota and severity and progression of arterial stiffness were assessed using MaAsLin2 software after adjustment for age,sex,and mean arterial blood pressure and correction for multiple testing.Gene“catalogs”were aligned to the Kyoto Encyclopedia of Genes and Genomes(KEGG)database to obtain information for potential functional capacities of the gut microbiota.Results:In this study,14 genera and 50 species of bacteria were identified to be abundant in participants with normal arterial stiffness compared with those with increased arterial stiffness.Of 14 genera,the prevalence of beneficial bacteria of the genera Leadbetterella and Cytophaga was correlated inversely with baPWV(P<0.05).Analyses of functional capacity revealed gut-microbial dysfunctions in the synthetic processes of“threonine dehydratase”“hypothetical protein”“mannosyl transferase”and“type-IV secretion-system proteins”in individuals suffering from arterial stiffness.During follow-up,bacteria of the proinflammatory genera Escherichia,Shigella,and Ruegeria were enriched in individuals with increased baPWV.Functional analyses showed that 26 KEGG orthologs of gut microbes were associated with an increase in baPWV and involved in“carbohydrate metabolism”“amino acid metabolism”and“protein families related to genetic information processing.”Conclusions:The composition and functional capacity of the microbial community in the gut of people suffering from arterial stiffness differed from those in individuals not suffering from arterial stiffness.Our data provide a new direction for the causality of the host-gut microbiota in arterial stiffness.

Association between non-alcoholic fatty liver disease and arterial stiffness in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population

Background and objective： Non-alcoholic fatty liver disease（NAFLD） is associated with arterial stiffness in the general population. Age, obesity, hypertension, and diabetics are risk factors for arterial stiffness. In this study, we aimed to investigate the association between NAFLD and arterial stiffness as measured by brachial-ankle pulse wave velocity（baPWV） in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population. Methods： A cross-sectional study with 1296 non-obese, non-hypertensive, and non-diabetic young and middle-aged（20–65 years） subjects undergoing routine medical check-ups in the International Health Care Center of the Second Affiliated Hospital of School of Medicine of Zhejiang University was carried out. Fatty liver was diagnosed by ultrasonography, and baPWV was measured using an automatic waveform analyzer. The subjects were classified into two groups according to the presence of NAFLD, and divided into a further two groups according to their baPWV. Results： The overall incidence of NAFLD was 19.0%, and NAFLD patients had a significantly higher level of baPWV than the controls（（1321±158） cm/s vs.（1244±154） cm/s; P〈0.001）. The incidence of NAFLD was clearly higher in the increased baPWV group than in the normal baPWV group（29.3% vs. 16.9%; P〈0.001）, and the incidence increased in line with the increase of baPWV quartiles in the normal range as well as with the severity of arterial stiffness（both P for trend 〈0.001）. Multiple linear logistic regression analysis showed that the presence of NAFLD was positively and independently associated with baPWV. Conclusions： Our results suggest that the presence of NAFLD is associated with arterial stiffness as measured by baPWV in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population.

The relationship and predictive value of plasma miR-21 with subclinical atherosclerosis in hypertension patients

Background Atherosclerosis is a major health problem worldwide. Previous studies have shown that miR- NAs are related to atherosclerosis. However, the relationship between miR-21 and atherosclerosis remains un- known. Therefore, this study aimed to explore the relationship between plasma miR-21 expression level and subclinical atherosclerosis in patients with hypertension. Methods We assessed the plasma level of miR-21 in 50 hypertension patients and in 30 age- and sexmatched healthy individuals. All patients underwent brachial-ankle pulse wave velocity （baPWV）, office and ambulatory blood pressure monitoring. Quantitative reverse transcrip- tase polymerase chain reaction （qRT-PCR） was used to measure miR-21. The correlations between miR-21 level and blood pressure parameters and baPWV were assessed using the Pearson correlation coefficient. Receiver op- erating characteristic （ROC） curve was constructed for distinguishing from atherosclerosis and healthy. Results The baseline data of all the participants such as fasting blood glucose, body mass index, serum lipid, hepatic and renal function were not significantly different between hypertension and control groups, as well as atherosclerosis and non-atherosclerosis groups （P〉0.05）. The hypertensive patients showed higher plasma miR-21 （32.99±3.01 vs. 26.14±1.03; P〈0.001） level as compared to controls, and in atherosclerosis group （33.53±2.86 vs. 28.56±3.66; P=0.002） than that in non-atherosclerosis group. MiR-21 level was significant positively correlated with 24h mean SBP （r=0.718, P〈0.001）, 24 h mean DBP （r=0.247 P=0.027）, office SBP （r=0.644, P〈0.001）, office DBP （r=0.316, P=0.004） and baPWV （r=0.714, P〈0.001）, respectively. The miR-21 for distinguishing atherosclerosis from healthy yielded an area under the ROC curve of 0.844 （95%CI： 0.758, 0.930; P〈0.001）. Conclusion Our data provide significant evidence that circulating miR-21 may represent potential non-invasive marker of athero-sclerosis in essential hypertensive patients.

Plasma miR-92a as a promising predictive biomarker for arteriosclerosis in patients with essential hypertension

Background MicroRNA （miR）-92a has been demonstrated to be associated with atherosclerosis through different ways. However, there are limited date about the association of miR-92a with arteriosclerosis in hypertensive patients. Methods We assessed the plasma level of miR-92a in 110 patients with untreated essential hypertension and 65 healthy individuals. All patients underwent the measurement of brachial-ankle pulse wave velocity （baPWV） and ambulatory blood pressure. Quantitative reverse transcriptase polymerase chain reaction （qRT- PCR） was used to evaluate level of miR-92a. The correlations of miR-92a with blood pressure parameters and baPWV were assessed using the Spearman correlation coefficient. Receiver operating characteristic （ROC） curve was constructed and the area under the ROC curve （AUC） was generated to assess the diagnostic value of miR- 92a for arteriosclerosis. Results The plasma level of miR-92a was significantly higher in hypertensive patients than in control individuals（31.03±3.13 vs. 25.00±2.99; P 〈0.001）,and higher in arteriosclerosis group than in unarteriosclerosis group（33.74±2.43 vs. 27.51±3.28; P〈0.001）. There were significantly positive correlations between MiR-92a level with 24 h mean SBP（r=0.874, P〈0.001）, 24h mean DBP（r=0.680, P〈0.001） and baPWV（r=0.685, P〈0.001）. ROC curve analyses revealed that the AUC value for miR-92a was 0.929 （95%CI： 0.886, 0.973; P〈 0.001）. Conclusions The level of miR-92a is positively related to baPWV, and holds great potential to be a noninvasive screening marker for arteriosclerosis in essential hypertensive patients.