Presence Of Microvascular Disease Research Articles

Microvascular disease and severe COVID-19 outcomes in UKBiobank participants with diabetes.

Early in the COVID-19 pandemic, evidence emerged suggesting that people with diabetic retinopathy (DR) or other microvascular diseases had greater risk of severe short-term outcomes. This study evaluated longer-term outcomes, providing more generalisable evidence. We identified a cohort of UKBiobank participants with diabetes and retrieved their diagnostic codes for a variety of microvascular diseases, complications of diabetes and systemic comorbidities. We investigated relationships between diagnoses and the study outcome: admission to Critical Care or death from COVID-19, taking age, sex and diabetes duration into account. We tested relationships, adding baseline covariates and weighting diagnostic codes according to their recency prior to COVID-19 diagnosis. In univariate analyses, DR (OR: 1·519, p = 0·016) and microvascular disease (OR: 2·001, p = 0·000) were associated with greater risk of the outcome. In multivariate analyses, as expected, respiratory disease was most strongly associated with the study outcome, microvascular disease second. Adjusting analyses by number of admissions (general health proxy) and weighted diagnostic coding (comorbidity severity at COVID-19 diagnosis indicator), did not improve predictive power of the model. The presence of microvascular disease in routinely-collected healthcare data predicts risk of COVID-19 severe outcomes, independently of general health, in a cohort of people with diabetes.

Association Between Microvascular Disease and Cardiorespiratory Fitness Among Adults With Type 2 Diabetes.

Little is known about the extent to which microvascular disease is associated with cardiorespiratory fitness (CRF) among individuals with type 2 diabetes. A total of 4,766 participants with type 2 diabetes underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study at baseline. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Microvascular disease was defined as having one or more of diabetes-related kidney disease (DKD), retinopathy, and neuropathy. The burden of microvascular disease was defined as the number of microvascular beds affected. Of the 4,766 participants (mean age 58.9 ± 6.7 years, 58.5% women, 66.1% White individuals), 1,761 (37%) had microvascular disease. Participants with microvascular complications in three vascular territories had a lower CFR than those without any microvascular disease (mean adjusted metabolic equivalent of task [MET] 6.58 vs. 7.26, P = 0.001). Participants with any microvascular disease had higher odds of low CRF than those without microvascular disease (adjusted odds ratio [OR] 1.45, 95% CI 1.24-1.71). An increasing burden of microvascular disease was associated with higher odds of low CRF (for microvascular disease in three vascular territories, adjusted OR 2.82, 95% CI 1.36-5.85). Adjusted ORs for low CRF were 1.24 (95% CI 0.99-1.55), 1.34 (95% CI 1.02-1.76), and 1.44 (95% CI 1.20-1.73) for neuropathy, retinopathy, and DKD associations, respectively. In a large cohort of adults with type 2 diabetes, the presence of microvascular disease and its burden were independently associated with lower CRF.

Microvascular development and remodeling

Skeletal fragility is an important complication of Type 1 Diabetes (T1D), particularly among older adults. Microvascular disease (MVD) has been linked to worse bone health in T1D, suggesting a potential direct pathophysiologic link between vascular disease and bone deficits. However, bone vascular control has not been explored in the context of T1D. Thus, this preliminary work investigates key mechanisms of regulation of the bone vasculature in older adults with T1D. Myogenic vasoconstriction and reactive hyperemia of tibial blood flow were assessed in older healthy adults (n=9, 65 ± 7 yrs) and older adults with T1D (n=10, 63 ± 6 yrs). Myogenic vasoconstriction was assessed in response to leg dependency (two levels of increased arterial transmural pressure obtained by lowering the leg below heart level) and reactive hyperemia was assessed in response to lower leg arterial occlusion via thigh cuff inflation. The initial peak reactive hyperemic response was considered a surrogate of myogenic vasodilation. For both stimuli, tibial blood flow was assessed via NIRS as total hemoglobin (tHb) and whole leg blood flow velocity (LBF) in the popliteal artery of the same leg was measured via Doppler ultrasound. Data are presented as mean±standard error. In response to leg dependency, with increased perfusion pressure, older adults had a tendency for smaller declines in LBF (L1: -3.85 ± 2.01 cm/s; L2: -6.22 ± 4.19 cm/s) compared to older adults with T1D (L1: -6.14 ±2.24 cm/s; L2: -10.4 ± 1.90 cm/s; group p=0.06, level p=0.07). Tibial tHb did not decline in older adults (L1: 1.16 ± 7.27 M; L2: 9.11 ± 13.8 M), but decreased progressively in those with T1D (L1: - 3.40 ± 2.79 M, L2: -6.14 ± 2.24 M, group p<0.01, group*level p=0.07), indicating pronounced tibial myogenic vasoconstriction. In response to reactive hyperemia, LBF increased rapidly with cuff release in both groups (older adults: 50.8 ±22.7cm/s; T1D: 40.0 ± 13.4cm/s). Despite similar responses in LBF, tibial tHb surpassed baseline values in older adults (1.50 ± 5.35M), whereas tibial tHb did not reach baseline values within 5 min post cuff release in T1D (-2.85 ± 5.09M, p=0.09), indicating impaired tibial myogenic vasodilation. Interestingly, older adults with T1D and MVD (n=5) had a stronger tendency for greater tibial myogenic vasoconstriction at both levels and significantly impaired reactive hyperemic response compared to those with no MVD (n=5). Our preliminary results indicate that older adults with T1D have greater myogenic vasoconstriction and impaired reactive hyperemic responses that appear to be worse in the presence of MVD. Alterations in myogenic control act to compromise blood flow regulation, restricting blood flow to bone, and potentially contributing to diabetes-inducted skeletal fragility. NIH NIDDK R01 DK124710. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Burden of Microvascular Disease and Risk of Atrial Fibrillation in Adults with Type 2 Diabetes

BackgroundEpidemiological data on the associations of microvascular disease with atrial fibrillation are scarce. We evaluated the associations of diabetes-related microvascular disease in multiple vascular beds and its burden with incident atrial fibrillation among adults with type 2 diabetes. MethodsA total of 7603 participants with type 2 diabetes and without atrial fibrillation were assessed for diabetic kidney disease, retinopathy, or neuropathy at baseline in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Incident atrial fibrillation events were adjudicated using follow-up electrocardiograms. Modified Poisson regression was used to generate risk ratios (RRs) and 95% confidence intervals (CIs) for atrial fibrillation. ResultsOf the 7603 participants (mean age 62.5 years, 38.0% women, 63.4% white), 63.3% (n = 4816) had microvascular disease—defined as the presence of ≥1 of: diabetic kidney disease, retinopathy, or neuropathy at baseline. Over a median of 7 years, there were 137 atrial fibrillation events (1.8%). Participants with microvascular disease had a 1.9-fold higher risk of incident atrial fibrillation compared with those without microvascular disease (RR 1.88; 95% CI, 1.20-2.95). Compared with no microvascular disease, the RRs for atrial fibrillation were 1.62 (95% CI, 1.01-2.61) and 2.47 (95% CI, 1.46-4.16) for those with 1 and ≥2 microvascular territories affected, respectively. The RRs for atrial fibrillation by type of microvascular disease were 1.57 (95% CI, 1.09-2.26), 0.95 (95% CI, 0.53-1.70), and 1.67 (95% CI, 1.15-2.44) for neuropathy, retinopathy, and diabetic kidney disease, respectively. ConclusionsIn a large cohort of adults with type 2 diabetes, the presence of microvascular disease and its burden were independently associated with higher risk of incident atrial fibrillation.

Comparison Between 5- and 1-Year Outcomes Using Cutoff Values of Pressure Drop Coefficient and Fractional Flow Reserve for Diagnosing Coronary Artery Diseases.

BackgroundThe current pressure-based coronary diagnostic index, fractional flow reserve (FFR), has a limited efficacy in the presence of microvascular disease (MVD). To overcome the limitations of FFR, the objective is to assess the recently introduced pressure drop coefficient (CDP), a fundamental fluid dynamics-based combined pressure–flow index.MethodsWe hypothesize that CDP will result in improved clinical outcomes in comparison to FFR. To test the hypothesis, chi-square test was performed to compare the percent major adverse cardiac events (%MACE) at 5 years between (a) FFR < 0.75 and CDP > 27.9 and (b) FFR < 0.80 and CDP > 25.4 groups using a prospective cohort study. Furthermore, Kaplan–Meier survival curves were compared between the FFR and CDP groups. The results were considered statistically significant for p < 0.05. The outcomes of the CDP arm were presumptive as clinical decision was solely based on the FFR.ResultsFor the complete patient group, the %MACE in the CDP > 27.9 group (10 out of 35, 29%) was lower in comparison to the FFR < 0.75 group (11 out of 20, 55%), and the difference was near significant (p = 0.05). The survival analysis showed a significantly higher survival rate (p = 0.01) in the CDP > 27.9 group (n = 35) when compared to the FFR < 0.75 group (n = 20). The results remained similar for the FFR = 0.80 cutoff. The comparison of the 5-year MACE outcomes with the 1-year outcomes for the complete patient group showed similar trends, with a higher statistical significance for a longer follow-up period of 5 years.ConclusionBased on the MACE and survival analysis outcomes, CDP could possibly be an alternate diagnostic index for decision-making in the cardiac catheterization laboratory.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT01719016.

Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes.

We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study followed for >35 years. Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from CVD, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on electrocardiogram, confirmed angina, or coronary artery revascularization. Cox proportional hazards models assessed the association of microvascular complications with subsequent risk of CVD. A total of 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively), associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER ≥30 mg/24 h occurring alone and/or with eGFR <60 mL/min/1.73 m2 and the presence of both retinal and kidney disease remained associated with CVD. Advanced microvascular disease, especially moderate to severe albuminuria or eGFR <60 mL/min/1.73 m2, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort.

Microvascular disease, peripheral artery disease, and the risk of lower limb amputation

Abstract Background Peripheral artery disease (PAD) is the leading cause of non-traumatic lower limb amputation. Microvascular disease (peripheral neuropathy, nephropathy, or retinopathy) increases the risk of lower limb amputation in patients with established PAD. Purpose We estimated risk of lower limb amputation associated with microvascular disease and PAD in a Danish cohort. Methods We conducted a population-based cohort study of every person living in Western Denmark aged 50–75 years on January 1, 2012 and followed them for 7 years. People with previous lower limb amputation were excluded. People were stratified by the presence of microvascular disease (peripheral neuropathy, nephropathy, or retinopathy) and PAD (peripheral atherosclerosis including intermittent claudication, or previous lower limb revascularization). We estimated the 7-year cumulative incidence and hazard ratio (HR) of lower limb amputation using individuals with neither microvascular disease nor PAD as reference. We also provide a sex-specific analyses and estimated the population attributable fraction of amputation associated with male sex. Results We included 933,597 individuals, of whom 16,007 had microvascular disease, 18,400 had PAD, and 1,789 had both microvascular disease and PAD. Patients with either microvascular disease (3.7%) or PAD (3.9%) had similar unadjusted 7-year risks of lower limb amputation (Figure). Microvascular disease (adjusted HR 3.21, 95% CI 2.86–3.59) and PAD (adjusted HR 7.37, 95% CI 6.68–8.14) increased the risk of lower limb amputation separately in adjusted analysis. Individuals with both microvascular disease and PAD had the highest risk of amputation (adjusted HR 11.82, 95% CI 10.11–13.80). While the relative impact of microvascular disease and PAD were similar in men and women, men had increased risk of amputation compared to women, in absolute terms. The population attributable fraction of amputations associated with male sex was 31%. Conclusion Microvascular disease and PAD are independently associated with a 3-fold and 7-fold increase of amputation rate, respectively. Combined, microvascular disease and PAD had an additive effect constituting a 12-fold amputation risk. Amputation risk was higher in men than in women, with 3 in 10 lower limb amputations in Western Denmark attributable to male sex. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Department of Cardiology, Aarhus University Hospital

Falling Insulin Requirements and Adverse Pregnancy Outcomes in Women With Pre-pregnancy Diabetes [10D

INTRODUCTION: A subset of women with pre-gestational diabetes experience a third-trimester fall in insulin requirements (IR). There is no consensus on whether this fall represents placental dysfunction or is a variant of normal third-trimester physiology. Our study sought to determine whether a third-trimester drop in IR is associated with adverse pregnancy outcomes. METHODS: This is a retrospective cohort study of women with type 1 and 2 diabetes. We compared outcomes in those with and without a ≥15% drop in basal IR. The primary outcome was a composite of stillbirth, spontaneous preterm birth, preterm premature rupture of membranes and iatrogenic preterm birth or emergency caesarean delivery for fetal wellbeing concerns. The results were adjusted for the effect of maternal BMI, presence of microvascular disease, and pre-pregnancy hemoglobin A1c &gt;7. The study was approved by the research ethics board at Mount Sinai Hospital. RESULTS: We included 350 women (146 type 1, 204 type 2), of which 15% had a drop of ≥15% in third-trimester basal insulin requirements. There was no difference in the primary outcome between groups (aOR 0.75 [0.27, 1.81]). In isolation the sensitivity and specificity of a ≥15% drop in basal IR as a diagnostic test for the primary outcome was 13% and 85%, respectively. CONCLUSION: A ≥15% drop in third-trimester basal IR is not associated with and is a poor predictor of adverse pregnancy outcomes in women with pre-pregnancy diabetes. It should not be used in isolation as a sole indication for delivery.

The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography\u2014The Maastricht Study

SummaryIn this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites.IntroductionTo examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters.MethodsCross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history.ResultsAfter full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters.ConclusionsIn this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.

Reduced global myocardial perfusion reserve in DCM and HCM patients assessed by CMR-based velocity-encoded coronary sinus flow measurements and first-pass perfusion imaging.

Coronary microvascular dysfunction (CMD) is an independent predictor of poor prognosis in patients suffering from dilative or hypertrophic cardiomyopathy (DCM/HCM). To assess CMD, quantitative myocardial first-pass perfusion (1P) cardiovascular magnetic resonance (CMR) can be performed. Coronary sinus flow (CSF) measurements at rest and during maximal vasodilatation are an alternative and well-validated approach for the quantification of global myocardial blood flow (MBF) in CMR. Global myocardial perfusion reserve (MPR) was used to compare both methods, 1P and CSF. This measure reflects the ratio of myocardial blood flow during maximal coronary vasodilatation over rest. 1P-MPR and CSF-MPR were calculated in 17 HCM patients, 14 DCM patients and 16 controls, who underwent a stress CMR study to rule out obstructive coronary artery disease. All patients were examined on a 1.5-T system and the study protocol comprised both, first-pass myocardial perfusion imaging (MPI) and velocity-encoded (VENC) phase-contrast imaging of CSF during rest and adenosine stress. 1P-MPR was significantly decreased only in HCM patients compared to controls (1.14 vs. 1.43, p = 0.045) whereas CSF-MPR was significantly reduced in both patient groups, HCM and DCM, compared to controls (2.38 and 2.07 vs. 3.18, p = 0.041 and p = 0.032). CSF-MBF at maximal stress was significantly lower in HCM and DCM patients compared to the control group (0.11 and 1.23 vs. 1.58ml/min/g, p = 0.008 and p = 0.040). A moderate but significant correlation between CSF-MPR and 1P-MPR was observed (r = 0.39, p = 0.011). A negative correlation between LV wall thickness and CSF-MBF at rest and stress was found in the DCM group using VENC-based CSF measurements (r=- 0.64, p = 0.013 and r=- 0.69, p = 0.006)-but not using 1P-MPI. Post-proceeding analysis regarding 1P-MPR and CSF-MPR measurements required 20.1 and 6.5min, respectively (p < 0.001). The presence of microvascular disease can be non-invasively and quickly detected by VENC-based CSF-MPR measurements during routine stress perfusion CMR in both HCM and DCM patients. Compared to conventional 1P-MPI, VENC-based CSF-MPR is particularly useful in DCM patients with thinned ventricular walls.

Comparative effects of microvascular and macrovascular disease on the risk of major outcomes in patients with type 2 diabetes

BackgroundMicrovascular disease is associated with a high risk of macrovascular events in patients with type 2 diabetes, but the impact of macrovascular disease on the risk of microvascular events remains unknown. We sought to evaluate the respective effects of prior microvascular and macrovascular disease on the risk of major outcomes, including microvascular events, in these patients.MethodsParticipants in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) trial (n = 11,140) and the ADVANCE-ON post-trial study (n = 8494) were categorized into 4 groups at baseline: dual absence of microvascular or macrovascular disease (n = 6789), presence of microvascular disease alone (n = 761), macrovascular disease alone (n = 3196), and both (n = 394). Outcomes were all-cause mortality, major macrovascular events (MACE), and major clinical microvascular events.ResultsAll-cause mortality, MACE, and major clinical microvascular events occurred in 2265 (20%), 2166 (19%), and 807 (7%) participants respectively, during a median follow-up of 9.9 (inter-quartile interval 5.6–10.9) years. The adjusted hazard ratios [95% CI] of death, MACE, and major clinical microvascular events were each greater in patients with baseline microvascular disease (1.43 [1.20–1.71], 1.64 [1.37–1.97], and 4.74 [3.86–5.82], respectively), macrovascular disease (1.43 [1.30–1.57], 2.04 [1.86–2.25], and 1.26 [1.06–1.51]) or both (2.01 [1.65–2.45], 2.92 [2.40–3.55], and 6.30 [4.93–8.06]) compared with those without these conditions. No interaction was observed between baseline microvascular and macrovascular disease for these events. The addition of microvascular disease (change in c-statistic [95% CI] 0.005 [0.002–0.008], p = 0.02) or macrovascular disease (0.005 [0.002–0.007], p < 0.0001) considered separately or together (0.011 [0.007–0.014], p < 0.0001) improved the discrimination and the classification (integrated discrimination improvement (IDI): 0.013 [0.010–0.016], p < 0.001; net reclassification improvement (NRI): 0.021 [0.011–0.032], p < 0.001) of the risk of all-cause mortality. Microvascular disease improved discrimination (0.009 [0.003–0.014]) and classification (IDI: 0.008 [0.006–0.010]; NRI: 0.011 [0.001–0.020]) of MACE. Baseline macrovascular disease modestly enhanced IDI (0.002 [0.001–0.002]) and NRI (0.041 [0.002–0.087]), but not discrimination, of major clinical microvascular events.ConclusionsMicrovascular and macrovascular disease are independently associated with the 10-year risk of death, MACE, and major clinical microvascular events in patients with type 2 diabetes. The coexistence of these conditions was associated with the highest risks.

Reduced Venous Compliance in Young Women with Type 1 Diabetes - Further Aggravated by Prolonged Elevated Levels of HbA1c.

Young patients with diabetes present with reduced compensatory responses to hypovolemic stress. Less compliant veins could be a contributing factor, since roughly two-thirds of the blood volume resides in the venous system as a blood reservoir, adjusting proper venous inflow to the heart. The aim of this study was to measure venous compliance and lower limb blood pooling during hypovolemic stress, and to correlate them to indices of diabetes severity and glucose control. Fifteen young women with type 1 diabetes (DW) and 18 healthy age-matched women (C) were subjected to lower body negative pressure (LBNP) (11-44 mmHg), creating hypovolemic stress. Lower limb blood pooling was measured with strain gage technique and venous compliance calculated as the relationship between ∆V/∆P. DW presented with reduced blood pooling (e.g., blood pooling during LBNP of 44 mmHg, DW, 1.69 ± 0.10; C, 2.10 ± 0.08 (ml/100 ml), and P = 0.003). Calculated venous compliance was also reduced in DW (e.g., compliance at 20 mmHg, DW, 0.046 ± 0.003; C, 0.059 ± 0.002 (ml/100 ml/mmHg), and P = 0.002). A progressive reduction in both venous compliance (P < 0.007) and blood pooling (P < 0.005) was seen with increasing level of HbA1c, and furthermore, less strongly associated with presence of microvascular disease (signs of retinopathy). Women with type 1 diabetes present with both reduced venous compliance and blood pooling. The reductions were particularly present in patients with long-standing poor glycemic control.

The MCP-1 Gene A-2518G Polymorphism Confers an Increased Risk of Vascular Complications in Type 2 Diabetes Mellitus Patients

We aimed to evaluate the correlation of the monocyte chemoattractant protein 1 (MCP-1) A-2518G polymorphism with type 2 diabetes mellitus (T2DM) and vascular complications in T2DM, to aid in understanding its role in pathogenesis. A total of 150 T2DM patients and 50 healthy controls (group A) were enrolled. The T2DM patients were divided into three groups based on the absence of complications (group B) presence of microvascular disease (group C) or macrovascular disease (group D). DNA of all enrolled subjects was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the MCP-1 A-2518G polymorphism. Serum MCP-1 levels were measured by an enzyme-linked immunosorbent assay (ELISA). Participants in group D had increased serum MCP-1 levels relative to group B, group C, and group A (all p<0.01). Compared with group A, the frequencies of the MCP-1 A-2518G G/G genotype and G allele were significantly higher in group C and group D (all p<0.05). In contrast to group B, group C had higher frequencies of the G/G genotype and G allele, while group D had higher G allele frequencies (all p<0.05). Logistic regression analysis showed that lower body-mass index (BMI) and free cholesterol (FC), as well as higher high-density lipoprotein cholesterol (HDL-C) levels may be the protective factors for T2DM, while higher levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and G/G genotype frequency were independent risk factors for T2DM. Our data indicates a correlation between the MCP-1 A-2518G polymorphism with macrovascular complications in T2DM patients; lower BMI and FC, as well as higher HDL-C levels may be the protective factors for T2DM, while higher levels of TG, LDL-C, and G/G genotype frequency were independent risk factors for T2DM.

Unrecognized Arteriosclerosis Is Associated with Wound Complications after Below-Knee Amputation

Guillotine below-knee amputation (BKA) for wet gangrene is an unfortunate complication of poorly controlled diabetes. We examined risk factors associated with wound complications after amputation formalization in this patient population. Retrospective data over a 4-year period were collected for patients undergoing guillotine BKA for wet gangrene followed by staged formalization. Patients with abnormal distal pulses underwent evaluation before formalization to stratify for peripheral arterial disease (PAD). Those patients with palpable pulses and no known PAD went to formalization without further investigation. Poor operative candidates underwent delayed formalization to allow for preoperative optimization. Patient history, interval between surgeries, pathology, and preformalization laboratories were tested for significance. Primary outcome was postformalization wound complication. Fifty-six amputations in 55 patients met inclusion criteria. Wound complications after formalization occurred in 18 cases, all BKAs (32%). A history of PAD was present in 19 patients (34.5%). On pathology, 23 patients (41%) had small-vessel atherosclerosis or arteriosclerosis. There was no association between wound complications and history of PAD (P = 0.4), preformalization albumin (P = 0.09), glucose (P = 0.9), white blood cell count (P = 0.4), or delayed versus expedited formalization (P = 0.8). Only the presence of microvascular disease on formal pathology was predictive of wound complications (P = 0.03). There was no association between microvascular disease on pathology and a history of PAD (P = 0.07). After formalization of lower extremity amputation for wet gangrene, traditional markers of PAD were not predictive of wound complications. Although formalization of guillotine BKA can safely be performed without significant delay, more thorough assessment of microvascular disease in the perioperative period may be useful in identifying patients at risk for wound failure.

A Case of Sick Sinus Syndrome in a Patient with Systemic Sclerosis

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Effect of myocardial contractility on hemodynamic end points under concomitant microvascular disease in a porcine model

In this study, coronary diagnostic parameters, pressure drop coefficient (CDP: ratio of trans-stenotic pressure drop to distal dynamic pressure), and lesion flow coefficient (LFC: ratio of % area stenosis (%AS) to the CDP at throat region), were evaluated to distinguish levels of %AS under varying contractility conditions, in the presence of microvascular disease (MVD). In 10 pigs, %AS and MVD were created using angioplasty balloons and 90-μm microspheres, respectively. Simultaneous measurements of pressure drop, left ventricular pressure (p), and velocity were obtained. Contractility was calculated as (dp/dt)max, categorized into low contractility <900 mmHg/s and high contractility >900 mmHg/s, and in each group, compared between %AS <50 and >50 using analysis of variance. In the presence of MVD, between the %AS <50 and >50 groups, values of CDP (71 ± 1.4 and 121 ± 1.3) and LFC (0.10 ± 0.04 and 0.19 ± 0.04) were significantly different (P < 0.05), under low-contractility conditions. A similar %AS trend was observed under high-contractility conditions (CDP: 18 ± 1.4 and 91 ± 1.4; LFC: 0.08 ± 0.04 and 0.25 ± 0.04). Under MVD conditions, similar to fractional flow reserve, CDP and LFC were not influenced by contractility.

Microvascular disease and motoric dysfunction

Buchman et al.1 report that the presence of microvascular disease (microinfarcts, cerebral amyloid angiopathy, and arteriolosclerosis) in brain autopsies done in 850 community-dwelling older adults was associated with motor impairments measured prior to death. These and other microvascular lesions such as cortical microbleeds are common in aging brains, but their clinical significance is not well-established.1,2 Some recent studies have linked microvascular lesions to risk of cognitive decline, but the relationship of this class of vascular lesions with various other geriatric syndromes is understudied. As with any retrospective study there are other role players (confounders, in epidemiology speak) that might explain the observed associations.1 However, even after accounting for several major confounders, including vascular risk factors and disease, interval between the last examination and death, and presence of terminal cognitive impairment or dementia, the relationship with motor dysfunction survived.1

Abstract 18705: Regional Variability of Microcirculatory Resistance After Successful Percutaneous Coronary Intervention

Background: The main drawback of Fractional Flow Reserve (FFR) measurements occurs in the presence of microvascular disease, as FFR does not take into consideration the contribution of abnormal microvascular resistance. Normal FFR with concomitant microcirculatory disease may be a cause of angina symptoms or myocardial ischemia. Recently, the blood flow in the myocardium has been reported to show significant spatial heterogeneity. We assessed the hypothesis that heterogeneity of regional microvascular resistance exists in patients after successful percutaneous coronary intervention (PCI). Methods and Results: FFR and the index of microcirculatory resistance (IMR) were measured after successful PCI in 20 patients with native de novo discrete coronary lesions both in the territory of the culprit vessel and in the reference territory of non-culprit vessel. Hyperemic mean transmit time (Tmn) was used for the assessment of coronary flow. FFR value after PCI was 0.89 (IQR 0.82-0.96). IMR value in the culprit vessel was 18.8 (IQR 12.1-25.7), and 19.05 (IQR 14.3-26.7) in the non-culprit vessel, respectively. There was no significant relationship between these two regional measurements (r 2 =0.0128, p=ns). Mean difference between these two measures was 17.4 ± 15.9. The coefficients of variation of IMR were 75.7% in the culprit vessel, and 59.5% in the non-culprit vessel. There was a significant relationship between IMR and Tmn both in the culprit vessels (r=0.968, p&lt;0.0001) and non-culprit vessels (r=0.913, p&lt;0.0001). Conclusion: A considerable regional heterogeneity of coronary perfusion and microvascular resistance were observed in the present study. There is a high inter-subject, intra-subject, and interregional variability of coronary flow and microvascular resistance in patients after successful PCI. These results highlight the difficulty in establishing the limits of normal microvascular resistance or vasodilating response in patients with ischemic heart disease.

Effect of heart rate on hemodynamic endpoints under concomitant microvascular disease in a porcine model

Diagnosis of the ischemic power of epicardial stenosis with concomitant microvascular disease (MVD) is challenging during coronary interventions, especially under variable hemodynamic factors like heart rate (HR). The goal of this study is to assess the influence of variable HR and percent area stenosis (%AS) in the presence of MVD on pressure drop coefficient (CDP; ratio of transstenotic pressure drop to the distal dynamic pressure) and lesion flow coefficient (LFC; ratio of %AS to the CDP at the throat region). We hypothesize that CDP and LFC are independent of HR. %AS and MVD were created using angioplasty balloons and 90-μm microspheres, respectively. Simultaneous measurements of pressure drop (DP) and velocity were done in 11 Yorkshire pigs. Fractional flow reserve (FFR), CDP, and LFC were calculated for the groups HR < 120 and HR > 120 beats/min, %AS < 50 and %AS > 50, and additionally for DP < 14 and DP > 14 mmHg, and analyzed using regression and ANOVA analysis. Regression analysis showed independence between HR and the FFR, CDP, and LFC while it showed dependence between %AS and the FFR, CDP, and LFC. In the ANOVA analysis, for the HR < 120 beats/min and HR > 120 beats/min groups, the values of FFR (0.82 ± 0.02 and 0.82 ± 0.02), CDP (83.15 ± 26.19 and 98.62 ± 26.04), and LFC (0.16 ± 0.03 and 0.15 ± 0.03) were not significantly different (P > 0.05). However, for %AS < 50 and %AS > 50, the FFR (0.89 ± 0.02 and 0.75 ± 0.02), CDP (35.97 ± 25.79.10 and 143.80 ± 25.41), and LFC (0.09 ± 0.03 and 0.22 ± 0.03) were significantly different (P < 0.05). A similar trend was observed between the DP groups. Under MVD conditions, FFR, CDP, and LFC were not significantly influenced by changes in HR, while they can significantly distinguish %AS and DP groups.

Techniques for Phenotyping Coronary Artery Disease in the Cardiac Catheterization Laboratory for Applications in Translational Research

The catheterization laboratory is an excellent resource for translational research projects requiring phenotypic analysis of coronary artery disease. Coronary angiography, a traditional method of quantifying coronary disease, remains useful for describing the extent and the severity of angiographic coronary disease but is limited by the fact that angiography only depicts the effect of atherosclerosis on the arterial lumen. For this reason, quantitative coronary angiography has been supplemented by intravascular ultrasound and other catheter-based techniques and non-invasive methods for studies involving atherosclerosis progression and regression. Other angiographic based techniques potentially useful in research include the semi-quantification of collateral circulation, thrombolysis in myocardial infarction (TIMI) frame count, and TIMI blush score. The invasive assessment of coronary flow reserve and fractional flow reserve is a valuable adjunctive technique and can be used to precisely quantify the extent of ischemia or the presence of microvascular disease. Intravascular ultrasound (IVUS) is currently considered the gold standard for early diagnosis of coronary atherosclerosis and for measuring plaque burden. The serial measurements of changes in plaque volume over time are a valuable method of discerning plaque progression and regression. Similarly, radiofrequency backscatter IVUS, a relatively new imaging modality, can be used to describe and track changes in plaque composition.