Vascular Medicine

Diabetes has been inconsistently associated with increased risk of venous thromboembolism (VTE) and there is little direct evidence on the associations of glycemia levels with VTE. We used data from the Atherosclerosis Risk in Communities study to test the hypothesis that glycemia, as measured by hemoglobin A_1c (A_1c), is positively associated with VTE. Participants aged 45–64 years (n = 12,298) had A_1c measured in 1990 and were followed for incident VTE (n = 345) through 2005. Because A_1c is affected by diabetes treatment, analyses were stratified by history of diagnosed diabetes. Owing to evidence of non-linearity, we categorized A_1c according to clinical cut-points: <5.7, 5.7–6.4, and ≥6.5% in those with no diagnosed diabetes; <7.0 and ≥7.0% in those with diagnosed diabetes. After adjustment for potential confounders, the hazard ratios (95% CIs) for VTE across increasing A_1c categories were 1 (referent), 1.02 (0.77, 1.35) and 0.72 (0.41, 1.29) for those without diagnosed diabetes, and 1.30 (0.77, 2.17) and 1.41 (0.95, 2.09) for those with diagnosed diabetes. To explore the relation, we employed various models to adjust for potential confounding variables and modeled A_1c as tertiles. We consistently found elevated hazard ratios in those with diagnosed diabetes, though the association was not statistically significant in every model. Hazard ratios in those without diagnosed diabetes were close to 1. In conclusion, our results are mildly suggestive that diagnosed diabetes and high levels of glucose, per se, may increase the risk of VTE. Elevated glucose was not related to VTE in those without diagnosed diabetes.

Impaired fasting glucose (IFG) in diabetes is a risk factor for arterial stiffness and cardiovascular disease (CVD), but the impact of a slightly high-normal glucose level remains controversial. We investigated whether slightly high-normal fasting plasma glucose (FPG) was independently associated with arterial stiffness in non-diabetic community-dwelling persons. We recruited 114 men aged 69 ± 9 years (range 40–89) and 208 women aged 68 ± 7 years (range 36–84) during their annual health examination in a single community. Arterial stiffness was evaluated by the mean of the right and left brachial–ankle pulse wave velocity (ba-PWV). Age-adjusted ba-PWV increased significantly from the lowest to the highest FPG group (p < 0.001). Multiple linear regression analyses for ba-PWV revealed that FPG levels (β=0.154, p < 0.001) were independently and significantly associated with ba-PWV. The multivariate-adjusted ba-PWV value of the high-normal glucose group (Group 3: 95–100 mg/dL) was significantly higher than that of the lowest normal glucose group (Group 1: 52–89 mg/dL) (p=0.021), and the ba-PWV value in the IFG group (Group 4: 101–125 mg/dL) was significantly higher than those of the normal glucose groups (Group 1: <90 mg/dL; Group 2: 90–94 mg/dL) (p<0.001 and p=0.009, respectively). Slightly high-normal glucose levels were associated with arterial stiffness in Japanese community-dwelling persons.

We investigated patients with a primary diagnosis of peripheral artery disease (n = 69) and coronary heart disease (CAD; n = 520) at baseline and on changes in psychosocial risk factors (depression, anxiety, quality of life, negative and positive affect) during a cardiovascular rehabilitation program. Patients completed psychosocial questionnaires at the beginning and at discharge of a 12-week rehabilitation program. Depression and anxiety were measured with the Hospital Anxiety and Depression Scale (HADS), positive and negative affect with the Global Mood Scale, and health-related quality of life with the SF-36 Health Survey. Patients with PAD showed improvements in anxiety (p < 0.001), negative affect (p < 0.001) and bodily pain (p < 0.001). Patients with CAD reported significant improvements in all measured dimensions (all p-values < 0.001).

Despite current consensus guidelines recommending intensive cardiovascular risk factor management for peripheral artery disease (PAD), patients suffering from PAD continue to experience significant morbidity and mortality. This excess morbid burden is at least partially related to impaired vascular function and systemic inflammation. Interventions bridging this gap are critical. Dietary supplementation of n-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to improve endothelial function and reduce inflammation in different cohorts, as well as to decrease cardiovascular events in secondary prevention trials in patients with coronary artery disease. Their effects in the PAD population are, however, less well understood. The OMEGA-PAD trial is a double-blinded, randomized, placebo-controlled trial that examines the impact of a high-dose, short-duration dietary oral supplementation of n-3 PUFA on vascular function and inflammation in patients with established PAD. The purpose of this article is to provide a detailed description of the design and methods of the OMEGA-PAD trial, and a summary of baseline characteristics of the cohort. ClinicalTrials.gov Identifier: NCT01310270

Aortic manipulation releases embolic material, thereby enhancing the probability of adverse neurologic outcomes following coronary artery bypass grafting (CABG). We prospectively evaluated 59 patients undergoing CABG. Patients in the single (SC, n = 37) and multiple clamp (MC, n = 22) groups were comparable in relation to age and operative risk (p > 0.05). Neurocognitive evaluation consisted of the Auditory Verbal Learning Test (AVLT), Color Trails Test A, the Grooved Pegboard test and the Mini-Mental State Examination. Data acquisition was performed preoperatively, early postoperatively and at the 4-month follow-up. Intraoperative transcranial Doppler (TCD) monitoring was used to quantify the embolic load in relation to different aortic clamping strategies. Preoperative neurocognitive results were similar between the groups (p > 0.05). The incidence of postoperative delirium was greater in the MC group but this failed to reach statistical significance (23% vs 8%, p = 0.14). SC patients had fewer embolization signals (270 ± 181 vs 465 ± 160, p < 0.0001). Early postoperative neurocognitive results were depressed in comparison to preoperative values in both groups (p < 0.05 for multiple comparisons). The magnitude of this cognitive depression was greater in the MC group (p < 0.05 for multiple comparisons). Preoperative levels of neurocognition were restored at follow-up in the SC group in all tests except the AVLT. A trend towards improvements in neurocognitive performances at follow-up was also observed in the MC group. Residual attention, motor skill and memory deficits were, however, documented with multiple tests. In conclusion, the embolic burden was significantly lower in the SC group. This TCD imaging outcome translated into fewer early cognition deficits and superior late restoration of function.

Cytokine receptor subunits are released from cells in a regulated manner and circulate in soluble forms at concentrations that are orders of magnitude greater than the concentrations of the cytokines themselves. The purpose of this study was to determine if the circulating concentrations of soluble receptor subunits for interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) might serve as early indicators of vascular dysfunction independent of the traditional cardiovascular disease (CVD) risk factors in women. Healthy women, aged 20–50 years (n = 36), were assessed for circulating concentrations of the cytokines IL-1β, IL-6 and TNFα and the soluble cytokine receptor subunits interleukin-1 receptor type I (sIL-1RI), sIL-1RII, sIL-6Rα, glycoprotein 130 (s-gp130), soluble TNF receptor type 1 (sTNFR1), and sTNFR2, along with traditional CVD risk factors. Cytokine receptor subunit expression on mononuclear cells and the release of these subunits in vitro were also determined. Brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) were assessed by ultrasonography and Doppler probes. Circulating sIL-6Rα correlated negatively with FMD (r = −0.56, p = 0.007) independent of age and other CVD risk factors. Circulating sTNFR1 correlated positively with cfPWV (r = 0.60, p = 0.002). TNFR1 receptor expression on monocytes correlated positively with cIMT (r = 0.51, p = 0.004). Plasma concentrations of IL-1β, IL-6 and TNFα were not significantly associated with FMD, cIMT or cfPWV. These data suggest that the receptors for IL-6 and TNFα, rather than the cytokines themselves, may be better indicators of early vascular changes that are associated with CVD.

The aim of this study was to determine how genetic variants contribute to warfarin dosing variability when non-genetic factors are controlled. Thirty healthy subjects were subjected to a warfarin dosing algorithm with daily international normalized ratio (INR) measurements to INR ≥ 2.0, then off warfarin to INR ≤ 1.2. The primary outcome was the cumulative dose required to achieve INR ≥ 2.0 for 2 consecutive days. CYP2C9 (p=0.004) and VKORC1 (p=0.02) variant carriers required lower cumulative doses, and CYP4F2 carriers required higher doses (p=0.04). Subjects with variants in both CYP2C9 and VKORC1 required fewer days to reach INR ≥ 2.0 than wild-type subjects or those with variants in CYP2C9 or VKORC1 (p=0.01). Genetic contribution to dose variability (~62%) was greater than previously reported, suggesting that uncontrolled clinical variables influence the effect of these variants. In conclusion, genotype-guided warfarin-dosing algorithms may rely more on genetic variables in healthier individuals than in patients with clinical confounders. ClinicalTrials.gov Identifier: NCT01520402

We aimed to test the association between matrix metalloproteinase (MMP) genetic polymorphisms and (a) intima–media thickness in the common carotid (IMTcc) and (b) the presence of plaques in the carotid and femoral bifurcations. Carotid and femoral bifurcations were scanned with ultrasound in 762 Cypriot community dwellers (46% men) over the age of 40 years. IMTcc and the presence of plaques were recorded. The MMP1 1G/2G, MMP3 5A/6A, MMP7 -181A>G, MMP9 R279Q, and MMP12 -82A>G polymorphisms were determined with the TaqMan method. In men, the presence of plaques in any bifurcation was associated with the MMP9 279Q allele (OR_adjusted=4.50; 95% CI=2.0 to 10.1; p<0.001) and the MMP7 -181A allele was associated with the presence of femoral plaques (OR_adjusted=2.61; 95% CI=1.36 to 4.99; p=0.004). In women, the presence of femoral plaques was associated with the MMP12 -82G allele (OR_adjusted=1.9; 95% CI=1.14 to 3.16; p=0.014). Our results suggest that the effect of common MMP genotypes on plaque presence may be site- and sex-dependent.

Acute limb ischemia (ALI) is defined as a sudden decrease (<14 days) in limb perfusion causing a potential threat to limb viability. Endovascular treatment of ALI is an effective and appropriate primary treatment strategy in patients with a viable acutely ischemic limb due to a recent arterial occlusion. We present a case of acute limb ischemia and discuss percutaneous interventional treatment strategies including catheter-directed thrombolysis, rheolytic thrombectomy, and utilization of distal protection devices.

We determined whether 7T magnetic resonance angiography (MRA) could be used for clearly observing microvessels in a clinically asymptomatic patient with steno-occlusion of the middle cerebral artery (MCA). We utilized 3T magnetic resonance imaging to obtain the brain images of a clinically asymptomatic patient and noted MCA steno-occlusion. In comparison with 3T MRA, 7T MRA could clearly delineate the microvessels, including lenticulostriate arteries and presumed collaterals, and our observation was comparable to that with conventional digital subtraction angiography. We report an interesting case of a clinically asymptomatic patient with MCA steno-occlusion.