Association between serum 25(OH)D3 and cardiovascular morbidity and mortality in people with Type 2 diabetes: a community-based cohort study.

AIM: We aimed to explore the association between vitamin D and cardiovascular morbidity and mortality in people with Type 2 diabetes recruited from a community-based study because there is limited and inconsistent research of this group. METHODS: A prospective community-based cohort study among people aged 55-66 years with Type 2 diabetes as part of The Cardiovascular Risk in Type 2 Diabetes - A Prospective Study in Primary Care (CARDIPP). We analysed serum 25-hydroxyvitamin D3 [25(OH)D3 ] at baseline. Cox regression analyses were used to calculate hazard ratios (HR) for the first myocardial infarction, stroke or cardiovascular mortality according to 25(OH)D3 . RESULTS: We examined 698 people with a mean follow-up of 7.3 years. Serum 25(OH)D3 was inversely associated with the risk of cardiovascular morbidity and mortality: HR 0.98 [95% confidence interval (CI) 0.96 to 0.99, P = 0.001]. Compared with the fourth quartile (Q4) [25(OH)D3 > 61.8 nmol/l], HR (with 95% CI) was 3.46 (1.60 to 7.47) in Q1 [25(OH)D3 < 35.5 nmol/l] (P = 0.002); 2.26 (1.01 to 5.06) in Q2 [25(OH)D3 35.5-47.5 nmol/l] (P = 0.047); and 1.62 (0.70 to 3.76) in Q3 [25(OH)D3 47.5-61.8 nmol/l] (P = 0.26) when adjusting for age, sex and season. The results remained significant after adjusting also for cardiovascular risk factors, physiological variables including parathyroid hormone and previous cardiovascular disease (P = 0.027). CONCLUSIONS: Low 25(OH)D3 is associated with an increased risk of cardiovascular morbidity and mortality in people with Type 2 diabetes independent of parathyroid hormone. Vitamin D could be considered as a prognostic factor. Future studies are needed to explore whether vitamin D deficiency is a modifiable risk factor in Type 2 diabetes.

The impact of using sagittal abdominal diameter to predict major cardiovascular events in European patients with type 2 diabetes.

BACKGROUND AND AIMS: Obesity is associated with diabetes type 2 and one of the most important risk factors for cardiovascular disease. We explored if sagittal abdominal diameter (SAD) is a better predictor of major cardiovascular events than waist circumference (WC) and body mass index (BMI) in type 2 diabetes. METHODS AND RESULTS: The CARDIPP study consists of a cohort of patients with type 2 diabetes. In this study we used data from 635 participants with no previous myocardial infarction or stroke, with a mean follow-up time of 7.1 years. SAD, WC and BMI were measured at baseline and the end-point was first cardiovascular event, measured as a composite of ICD-10 codes for acute myocardial infarction, stroke or cardiovascular mortality. SAD was significantly higher in the major cardiovascular event group compared to participants that did not suffer a major cardiovascular event during follow-up (p < 0.001). SAD >25 cm was the only anthropometric measurement that remained associated with major cardiovascular events when adjusted for modifiable and non-modifiable factors (hazard ratio 2.81, 95% confidence interval 1.37-5.76, p = 0.005). CONCLUSION: SAD with the cut off level of >25 cm, if confirmed in larger studies, may be used as a more independent risk-assessment tool compared with WC in clinical practice, to identify persons with type 2 diabetes at high cardiovascular risk. ClinicalTrials.gov: NCT01049737.

Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years.

AIM: To explore prospectively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes. METHODS: We analysed data from 135 men and 53 women with Type 2 diabetes, aged 54-66 years. Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups: <5000 steps/day, 5000-7499 steps/day, 7500-9999 steps/day and ≥10 000 steps/day. Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years. RESULTS: The mean (±sd; range) number of steps/day was 8022 (±3765; 956-20 921). The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest. When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex, age, diabetes duration, HbA1c , BMI, systolic blood pressure, pulse wave velocity at baseline, ß-blocker use, statin use, unemployment, smoking and diabetes medication, the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity (P=0.005). Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s. CONCLUSIONS: We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.

Prediction of Post-interventional Outcome in Great Saphenous Vein Incompetence: The Role of Venous Plethysmography with Selective Superficial Vein Occlusion.

OBJECTIVE/BACKGROUND: To evaluate whether the outcome of radiofrequency ablation (RFA) treatment of great saphenous vein (GSV) incompetence may be predicted using strain-gauge plethysmography (SGP) with selective occlusion of the superficial venous system. METHODS: Seventeen patients (20 limbs) underwent endovenous RFA treatment for GSV incompetence (Clinical Etiology Anatomy Pathophysiology classification C2-C5; "C-group"). Duplex ultrasound (DUS) and SGP were performed with selective occlusion of superficial veins before and after RFA. Selective superficial occlusion was validated, in a control group (C-group) of 12 patients (14 legs), by ascending phlebography. In the RFA group, the time taken to reach 50% and 90% (T50, T90) of maximum venous volume was measured, as well as relative maximal reflux rates (%EV/min). The methodological error and coefficient of variation (CV) were assessed. RESULTS: Nineteen of 20 legs had complete post-operative GSV obliteration using DUS, and refilling times were improved after RFA (T50 11 ± 3 vs. 19 ± 3 s; p < .001; T90 27 ± 5 vs. 47 ± 6 s; p < .001). With SGP, the methodological error and CV for T50 were 4 s and 16%, respectively. Equivalence between pre-operative superficial occlusion and post-operative baseline measurements was achieved in 15 of 17 legs for T50, and 12 of 17 for T90 (three of the 20 legs were excluded due to treatment failure [n = 1], and untreated perforating veins [n = 2]). Mean differences (95% confidence interval) were within the equivalence ranges (T50 1 [-1 to 3] seconds; T90 -3 [-11 to 4] seconds). In the C-group superficial vein occlusion was possible in 12 of 14 legs. The remaining patient (two legs) showed incomplete superficial vein occlusion at ankle level (lipodermatosclerosis) and complete superficial vein occlusion at calf level. CONCLUSION: SGP with standardized superficial venous occlusion seems to be a reliable method for identifying venous reflux and may be useful in predicting the results of successful RFA treatment.

Lower prevalence than expected when screening 70-year-old men for abdominal aortic aneurysm.

BACKGROUND: Screening 65-year-old men for abdominal aortic aneurysms (AAA) is a cost-effective method to reduce the mortality from ruptured AAA. However, contemporary results show a lower than expected prevalence of AAA, thus questioning the benefit of screening. Since the prevalence increases with age, a possible way to enhance the benefit of screening might be to screen older men. Our aim was to determine the contemporary screening-detected prevalence among 70-year-old men. METHODS: A total of 5,623 unscreened 70-year-old men were invited to ultrasound screening. Uni- and multivariable analyses were used to assess the risk factors for AAA. RESULTS: The attendance rate was 84.0%. The prevalence of previously unknown AAAs was 2.3%. When adding the 64 men with an already known AAA to the screening-detected ones, the total prevalence in the population was at least 3.0%, and the previously discovered AAAs constituted 37.4% of the total prevalence. "Ex smoker" and "Current smoker" were the most important risk factors. CONCLUSIONS: When screening 70-year-old men for AAA, the prevalence was less than half that expected, despite a high attendance rate. Smoking was the strongest risk factor. Almost 40% of the men with AAAs were already known from other means than screening.

Cardiovascular function in adulthood following intrauterine growth restriction with abnormal fetal blood flow.

OBJECTIVES: To examine whether intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life. METHODS: We examined 19 young adults (aged 22-25 years) who were born at term after IUGR, along with 18 controls. All had been examined previously with fetal Doppler, and in the present follow-up with echocardiography, carotid echo-tracking ultrasound, applanation tonometry, blood pressure and laser Doppler, in order to characterize their cardiac and vascular geometry and/or function. RESULTS: The diameter of the ascending aorta and the left ventricular diameter were smaller in the IUGR group, but only ascending aortic diameter remained significantly smaller after adjustment for body surface area (P < 0.05). The aortic pressure augmentation index was higher in the IUGR group (P < 0.05). The common carotid artery diameter, intima-media thickness and distensibility as well as left ventricular mass and function were similar in the two groups. IUGR status was found to be an independent predictor of ascending aortic diameter. CONCLUSIONS: IUGR due to placental dysfunction seems to contribute to the higher systolic blood pressure augmentation and the smaller aortic dimensions that are observed in adults more than 20 years later, with possible negative consequences for future left ventricular performance due to increased aortic impedance.

Pedometer-determined physical activity is linked to low systemic inflammation and low arterial stiffness in Type 2 diabetes.

AIMS: The aim of this study was to explore the association between pedometer-determined physical activity versus measures of obesity, inflammatory markers and arterial stiffness in people with Type 2 diabetes. METHODS: We analysed data from 224 men and 103 women with Type 2 diabetes, aged 54-66 years. Physical activity was measured with waist-mounted pedometers during three consecutive days and the number of steps/day were calculated and classified in four groups: < 5000 steps/day, 5000-7499 steps/day, 7500-9999 steps/day and ≥ 10000 steps/day. Blood samples were analysed for lipids, HbA(1c), inflammatory markers including C-reactive protein and interleukin-6. Nurses measured blood pressure and anthropometrics. Aortic pulse wave velocity was measured with applanation tonometry over the carotid and femoral arteries. RESULTS: Mean steps/day was 7683 ± 3883 (median 7222, interquartile range 4869-10,343). There were no differences in age, diabetes duration, blood pressure, lipids or glycaemic control between the four groups of pedometer-determined physical activity. Subjects with higher steps/day had lower BMI (28.8 vs. 31.5 kg/m(2), P < 0.001), waist circumference (101.7 vs. 108.0 cm, P < 0.001), lower levels of C-reactive protein (1.6 vs. 2.6 mg/l, P = 0.007), lower levels of interleukin-6 (1.9 vs. 3.8 pg ml, P < 0.001) and lower pulse wave velocity (10.2 vs. 11.0 m/s, P = 0.009) compared with less physically active people. CONCLUSIONS: We conclude that physical activity measured with pedometer was associated not only with less abdominal obesity, but also with decreased systemic low-grade inflammation as well as with low arterial stiffness, in people with Type 2 diabetes.

Impaired abdominal aortic wall integrity in elderly men carrying the angiotensin-converting enzyme D allele.

OBJECTIVE: A polymorphism in the angiotensin-converting-enzyme gene (ACE I/D) has been associated with abdominal aortic aneurysm and a link between aortic aneurysm and aortic stiffness has been suggested. This study aimed to explore the links between ACE I/D polymorphism, circulating ACE and abdominal aortic wall integrity as reflected by abdominal aortic wall stiffness. MATERIAL: A total of 212 men and 194 women, aged 70-88 years, were studied. METHODS: Mechanical properties of the abdominal aorta were determined using the Wall Track System, ACE genotype using the polymerase chain reaction (PCR) and circulating ACE level by enzyme-linked immunosorbent assay (ELISA). RESULTS: In men, pulsatile diameter change differed between genotypes (II 0.70, ID 0.55 and DD 0.60 mm, P = 0.048), whereas a tendency was seen for distensibility coefficient (DC) (II 10.38, ID 7.68 and ID 8.79, P = 0.058). Using a dominant model (II vs. ID/DD), men carrying the ACE D allele had lower pulsatile diameter change (P = 0.014) and DC (P = 0.017) than II carriers. Multiple regression analyses showed additional associations between the D allele and increased stiffness ß, and reduced compliance coefficient. CONCLUSION: Men carrying the ACE D allele have stiffer abdominal aortas compared with II carriers. Deranged abdominal aortic stiffness indicates impaired vessel wall integrity, which, along with other local predisposing factors, may be important in aneurysmal disease.

Masked nocturnal hypertension--a novel marker of risk in type 2 diabetes.

AIMS/HYPOTHESIS: This study was designed to evaluate the prevalence of masked nocturnal hypertension (MNHT) and its impact on arterial stiffness and central blood pressure in patients with type 2 diabetes. METHODS: Middle-aged patients (n = 414) with type 2 diabetes underwent clinic and ambulatory BP measurements and applanation tonometry. RESULTS: MNHT (clinic BP < 130/80 mmHg and night-time BP > or = 120/70 mmHg) was found in 7.2% of patients (n = 30). Compared with patients with both clinical and nocturnal normotension (n = 70), patients with MNHT had higher aortic pulse wave velocity (PWV) (10.2 +/- 1.8 m/s vs 9.4 +/- 1.7 m/s; p = 0.03) and higher central BP (117.6 +/- 13.9/74.0 +/- 9.1 mmHg vs 110.4 +/- 16.4/69.7 +/- 9.6 mmHg, p = 0.04). In patients with clinical normotension, night-time systolic BP correlated significantly with PWV. CONCLUSIONS/INTERPRETATION: Thirty per cent of patients with clinical normotension had nocturnal hypertension. This was accompanied by increased arterial stiffness and higher central BP. We conclude that in clinically normotensive patients with type 2 diabetes, ambulatory BP measurement may help clinicians to identify patients with increased cardiovascular risk.

Association of genetic variation on chromosome 9p21.3 and arterial stiffness.

OBJECTIVES: Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals. METHODS AND RESULTS: A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness. CONCLUSIONS: Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.

Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in middle-aged patients with Type 2 diabetes.

AIMS: To explore the association between carotid intima-media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with conventional lipids in middle-aged patients with Type 2 diabetes. METHODS: We analysed data from 247 patients with Type 2 diabetes, aged 55-66 years, in the Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden. RESULTS: The ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA(1c)) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA(1c), hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA-I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7-10.8, P = 0.002). CONCLUSIONS: We conclude that there was a significant association between the apoB/apoA-I ratio and IMT in middle-aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.

Vascular mechanical properties and endothelial function in pre-eclampsia with special reference to bilateral uterine artery notch.

OBJECTIVES: To assess whether women with pre-eclampsia (PE) have different properties of the blood vessel wall compared to healthy pregnant controls. Further, to evaluate endothelial function and vascular mechanical properties in women with PE with special regard to its association with bilateral uterine artery notch and placental histopathology. PARTICIPANTS: Some 57 Caucasian pregnant women: 23 with uncomplicated pregnancies and normal uterine artery Doppler, and 34 with PE, the PE group comprising 2 subgroups according to the presence (n=20) or absence (n=14) of bilateral uterine artery notches. METHODS: Ultrasonic echo-tracking assessed the elastic properties of the common carotid artery, abdominal aorta and popliteal artery. Flow-mediated dilatation (FMD) of the brachial artery was measured by ultrasonography. Histopathological examination of the placenta was carried out in 46 pregnancies: 18 uncomplicated pregnancies, 15 with PE with bilateral notch, and 13 with PE without bilateral notch. RESULTS: There were no significant differences in carotid, aortic or popliteal vessel wall stiffness either between women with PE and controls or within the PE group. FMD was significantly lower in women with PE than in controls (p=0.03). The lowest FMD was observed in pre-eclamptic women with bilateral uterine artery notches 9.5% (SD: 5.3) compared to 11.6% (SD: 5.4) in pre-eclamptic women without bilateral uterine artery notch, and 13.4% (SD: 4.0) in controls (p=0.01). Bilateral uterine artery notching was significantly associated with a lower FMD (OR: 0.87; 95% CI: 0.77-0.98). There were significantly more placentas with high ischaemic score in the bilateral notch group than in the group with PE and normal circulation. CONCLUSIONS: There were no differences in vessel wall stiffness between women with PE and healthy controls. Women with PE showed signs of endothelial dysfunction, significantly more pronounced in women with bilateral uterine artery notch. Bilateral uterine artery notch was associated with ischaemic pathology of the placenta. Notwithstanding, a significant number of placentas in the PE group failed to show noteworthy ischaemic or other morphological changes that could explain the role of the placenta in the development of PE.

A method for accurate localization of the first heart sound and possible applications.

We have previously developed a method for localization of the first heart sound (S1) using wavelet denoising and ECG-gated peak-picking. In this study, an additional enhancement step based on cross-correlation and ECG-gated ensemble averaging (EA) is presented. The main objective of the improved method was to localize S1 with very high temporal accuracy in (pseudo-) real time. The performance of S1 detection and localization, with and without EA enhancement, was evaluated on simulated as well as experimental data. The simulation study showed that EA enhancement reduced the localization error considerably and that S1 could be accurately localized at much lower signal-to-noise ratios. The experimental data were taken from ten healthy subjects at rest and during invoked hyper- and hypotension. For this material, the number of correct S1 detections increased from 91% to 98% when using EA enhancement. Improved performance was also demonstrated when EA enhancement was used for continuous tracking of blood pressure changes and for respiration monitoring via the electromechanical activation time. These are two typical applications where accurate localization of S1 is essential for the results.

Vascular characteristics in young women-Effect of extensive endurance training or a sedentary lifestyle.

AIM: To explore whether high-level endurance training in early age has an influence on the arterial wall properties in young women. METHODS: Forty-seven athletes (ATH) and 52 controls (CTR), all 17-25 years of age, were further divided into runners (RUN), whole-body endurance athletes (WBA), sedentary controls (SC) and normally active controls (AC). Two-dimensional ultrasound scanning of the carotid arteries was conducted to determine local common carotid artery (CCA) geometry and wall distensibility. Pulse waves were recorded with a tonometer to determine regional pulse wave velocity (PWV) and pulse pressure waveform. RESULTS: Carotid-radial PWV was lower in WBA than in RUN (P < .05), indicating higher arterial distensibility along the arm. Mean arterial pressure was lower in ATH than in CTR and in RUN than in WBA (P < .05). Synthesized aortic augmentation index (AI@75) was lower among ATH than among CTR (-12.8 ± 1.6 vs -2.6 ± 1.2%, P < .001) and in WBA than in RUN (-16.4 ± 2.5 vs -10.7 ± 2.0%, P < .05), suggesting a diminished return of reflection waves to the aorta during systole. Carotid-femoral PWV and intima-media thickness (IMT), lumen diameter and radial distensibility of the CCA were similar in ATH and CTR. CONCLUSION: Elastic artery distensibility and carotid artery IMT are not different in young women with extensive endurance training over several years and in those with sedentary lifestyle. On the other hand, our data suggest that long-term endurance training is associated with potentially favourable peripheral artery adaptation, especially in sports where upper body work is added. This adaptation, if persisting later in life, could contribute to lower cardiovascular risk.

Impaired vascular growth in late adolescence after intrauterine growth restriction.

BACKGROUND: Abnormal blood flow in a fetus small for gestational age indicates true fetal intrauterine growth restriction (IUGR). We tested the hypothesis that IUGR with abnormal fetal blood flow is associated with long-term abnormal vascular morphology and function in adolescence. METHODS AND RESULTS: In a prospective study, vascular mechanical properties of the common carotid artery (CCA), abdominal aorta, and popliteal artery (PA) were assessed by echo-tracking sonography in 21 adolescents with IUGR and abnormal fetal aortic blood flow and in 23 adolescents with normal fetal growth and normal fetal aortic blood flow. Endothelium-dependent and -independent vasodilatation of the brachial artery was measured by high-resolution ultrasound. After adjustment for body surface area and sex, the IUGR group had significantly smaller end-diastolic vessel diameters than the referents in the abdominal aorta and PA (mean difference, 1.7 mm [95% CI, 0.62 to 2.74] and 0.6 mm [95% CI, 0.25 to 1.02], respectively) (P=0.003 and P=0.002, respectively), with a similar trend in the CCA (P=0.09). A higher resting heart rate was observed in the IUGR group (P=0.01). No differences were found in stiffness or in endothelium-dependent and -independent vasodilatation between the 2 groups. CONCLUSIONS: IUGR caused by placental insufficiency appears to be associated with impaired vascular growth persisting into young adulthood in both men and women. The smaller aortic dimensions and the higher resting heart rate seen in adolescents with previous IUGR may be of importance for future cardiovascular health.

Pulse wave transit time for monitoring respiration rate.

In this study, we investigate the beat-to-beat respiratory fluctuations in pulse wave transit time (PTT) and its subcomponents, the cardiac pre-ejection period (PEP) and the vessel transit time (VTT) in ten healthy subjects. The three transit times were found to fluctuate in pace with respiration. When applying a simple breath detecting algorithm, 88% of the breaths seen in a respiration air-flow reference could be detected correctly in PTT. Corresponding numbers for PEP and VTT were 76 and 81%, respectively. The performance during hypo- and hypertension was investigated by invoking blood pressure changes. In these situations, the error rates in breath detection were significantly higher. PTT can be derived from signals already present in most standard monitoring set-ups. The transit time technology thus has prospects to become an interesting alternative for respiration rate monitoring.

The association between endostatin and kidney disease and mortality in patients with type 2 diabetes.

AIM: Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D). METHODS: This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality. RESULTS: Of the total study cohort, 20 patients declined by ≥20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR<60mL/min/1.73m2) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR)>3g/mol] had higher median levels of endostatin than those without nephropathy (62.7µg/L vs 57.4µg/L, respectively; P=0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (≥20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07). CONCLUSION: In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.

Influence of fibrillin-1 genotype on the aortic stiffness in men.

Aortic stiffness is a predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy men (range 28-81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 G>T polymorphism, were determined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype (P = 0.005). Pulse pressure also was increased in the 2-3 genotype (P = 0.04). There was no significant association between type 1 collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease.

Diameter and compliance in the human common carotid artery--variations with age and sex.

In this study, age and sex differences in diameter and compliance of the common carotid artery (CCA) were evaluated in 119 healthy subjects with a phase-locked echo-tracking system. The diameter and pulsatile diameter changes were measured, and pressure strain elastic modulus (Ep) and stiffness (beta) were calculated and used as the inverse estimate of compliance. The carotid diameter increased more rapidly in males and was larger than in females from 25 years of age. The relative diameter change was equal in both sexes, and decreased from 12% to 14% in younger subjects to approximately 5% in elderly subjects. Compliance decreased almost linearly and in parallel in males and females up to 45 years of age. Between 45 and 60 years the decrease was more marked in females than in males, whereas it was by far more marked in males between 60 and 70 years of age.

Stiffness and diameter of the common carotid artery and abdominal aorta in women.

Vascular disease is differentiated throughout the vascular regions with aorta more prone to dilatation and with peripheral arteries more prone to occlusive disease. In this study, we investigated the diameter and distensibility in the common carotid artery (CCA) and abdominal aorta (AO) in healthy females of varying ages to assess potential differences in the aging process. The diameter and pulsatile diameter change of the CCA and AO in 66 healthy Caucasian females aged 8 to 79 y were examined using an ultrasound phase-locked echo-tracking technique. Blood pressure was obtained by the auscultatory method. Arterial stiffness (beta) was calculated. The diameter of both CCA and AO increases, not only in childhood, but also in adult women. The dilatation in adults (25 to 75 y) seems to be more pronounced in the AO (23%) than in the CCA (11%). Stiffness (beta) is higher in the CCA than AO before 20 y of age (p < 0.05). Stiffness increases with aging in both arterial regions, but the increase is initially somewhat higher in the AO, which means that no differences between the CCA and AO are seen from 25 y onward. In conclusion, this study demonstrates regional differences in diameter change and stiffness in the CCA and AO, and implies that the AO is more prone to age-related changes of the arterial wall than the CCA. These differences, however, are not as marked as previously reported in males.