Ischemic Peripheral Vascular Disease Research Articles

An Overview of the Treatment Strategies of Extremities Ischemia in the Intensive Care Unit.

To investigate the effect of the peripheral block on peripheral ischemia on the extremities of patients in the intensive care unit (ICU). Sixty-two patients with ischemic peripheral vascular disease were divided retrospectively into two groups; Group 1 (patients who underwent USG-guided infraclavicular or femoral block, n=20) and Group 2 (patients who did not experience any block, n=42). The demographic characteristics of the patients, the diagnosis of hospitalization, the day when the circulatory disorder developed, laboratory tests at the time of diagnosis, other medical treatments applied, presence of inotropic support, the response of ischemia on extremities, amputation, duration of hospital stay, discharge and mortality were compared. The most common reason for hospitalization was cerebrovascular disease. There was no statistical difference between the groups regarding age, gender, height, body weight, and diagnosis. There was no statistical difference between the groups regarding hematocrit, lactate, creatinine, and albumin values, the day when the peripheral ischemia developed in extremities, inotropic and prednisolone use, presence of cannulation, length of hospital stays, and mortality. The number of patients discharged from the intensive care unit in Group 1 was significantly higher than in Group 2 (p=0.048). Amputation was performed on one patient in Group 1 and two patientsin Group 2. There was a decrease in peripheral ischemia in 14 (70%) of the patients in Group 1 and 25 (59.5%) of the patients in Group 2. Targeted peripheral block techniques for peripheral circulatory disorders for selected ICU patients in conjunction with preventive and medical treatments may decrease peripheral ischemia in extremities and increase ICU discharge.

MO987: Risk Predictors and Impact of Post-Transplant Cardiovascular Disease in A 20-Year Cohort of Kidney Transplant Recipients

Abstract BACKGROUND AND AIMS Although improvement in histocompatibility matching, immunosuppressive therapy and antimicrobial treatment have led to improved long-term allograft survival, cardiovascular diseases (CVD) remain the major cause of morbidity and mortality in kidney transplant recipients (KTR). In addition to the accumulated risks due to chronic kidney disease and dialysis, kidney transplantation conveys its own unique risk factors for CVD. These include the metabolic effects of immunosuppressive treatments such as post-transplant hyperglycaemia, dyslipidaemia and hypertension as well as the effects of suboptimal kidney function including volume overload, anaemia, mineral bone disease and left ventricular hypertrophy. The predictors of cardiovascular diseases in KTR, however, have not been clearly defined. This study aimed to first ascertain the incidence of post-transplant CVD in those KTR without a prior confirmed history of CVD, then identify the predictors of CVD transplant associated CVD risk factors and finally evaluate the impact of CVD on graft and patient survival in this era of modern immunosuppressive medications. METHOD We evaluated 962 KTR transplanted between 2000 and 2020 and followed in a single centre. About 328 KTR with a history of pre transplant CVD were excluded. CVD was defined as a composite of Ischaemic heart disease, myocardial infarction, heart failure, stroke or peripheral vascular disease. Logistic regression analyses were performed to identify the risk predictors of post-transplant CVD. Kaplan–Meier plots and multivariate Cox proportional hazards regression analysis were used to identify and characterize predictors of dialysis free survival. RESULTS Among 634 KTR included in the analysis (mean age: 45 ± 15 years), CVD was reported in 101 KTR (16%) during a median follow-up of 95.9 months. About 274(43%) were females, 531(84%) were Caucasians. KTR with post-transplant CVD were likely to be older (50 ± 13 versus 44 ± 15 years; P < 0.001), had spent more time on dialysis [median (IQR) 21 (1–51) versus 11 (0–3) months; P = 0.004] and received cyclosporin maintenance (18% versus 7%; P = 0.01). Incidence of post-transplant CVD was independently predicted by older age [OR: 1.40 (1.15–1.70: P = 0.001)], tacrolimus therapy [OR: 0.81 (0.71–0.93), P = 0.002], mean haemoglobin concentration [OR: 0.86 (0.75–1.00), P = 0.049] and average C-reactive protein (CRP) level [OR: 1.13 (1.02–1.25), P = 0.02] (Figure 1). The median dialysis free survival was significantly lower in KTR who developed post-transplant CVD (14.7 versus 20 years, P = 0.009). In the multivariate Cox regression analysis, the factors associated with worse dialysis free survival in our cohort (survival with a functioning graft) were older age at transplantation [hazard ratio (HR): 1.03; P < 0.001), a history of post-transplant CVD (HR: 1.68; P = 0.006), higher post-transplant parathormone levels (HR: 1.02; P < 0.001), higher mean urine protein creatinine ratio (uPCR) (HR: 1.003: P < 0.001), a greater annual rise in uPCR (HR: 1.002; P < 0.001) and a history of acute rejection (HR: 1.56; P = 0.03). Statin treatment was associated with better dialysis free survival outcome (HR: 0.60; P = 0.01). CONCLUSION The incidence of post-transplant CVD in KTR with no history of pre-transplant CVD was 16%. Age at transplantation and average CRP were independent predictors of post-transplant CVD whereas treatment with Tacrolimus was associated with a lower risk of CVD. Statin therapy was associated with better dialysis free survival whereas a higher PTH was linked to poor survival. It was interesting to note that diabetes was not independently associated with the risk and outcome of post-transplant CVD in our cohort.

Targeted delivery of nanomedicines for promoting vascular regeneration in ischemic diseases.

Ischemic diseases, the leading cause of disability and death, are caused by the restriction or blockage of blood flow in specific tissues, including ischemic cardiac, ischemic cerebrovascular and ischemic peripheral vascular diseases. The regeneration of functional vasculature network in ischemic tissues is essential for treatment of ischemic diseases. Direct delivery of pro-angiogenesis factors, such as VEGF, has demonstrated the effectiveness in ischemic disease therapy but suffering from several obstacles, such as low delivery efficacy in disease sites and uncontrolled modulation. In this review, we summarize the molecular mechanisms of inducing vascular regeneration, providing the guidance for designing the desired nanomedicines. We also introduce the delivery of various nanomedicines to ischemic tissues by passive or active targeting manner. To achieve the efficient delivery of nanomedicines in various ischemic diseases, we highlight targeted delivery of nanomedicines and controllable modulation of disease microenvironment using nanomedicines.

Variations in knee range of motion during repeat knee extension with an amputated lower leg at different contraction rhythms over 8 consecutive days in a patient with severe diabetic neuropathy: A clinical study

Background: This clinical study sought to understand the knee range of motion (KROM) in an amputated stump during repeat voluntary knee extension with or without a 0.5 kg weight in the acute/early phase after amputation can vary between different target knee extension rhythm frequency (KER) levels in the amputated lower leg of a patient with severe diabetic sensory disorder and leg ischemia. Case Presentation: A 51-year-old male patient with severe diabetic neuropathy had a right lower leg amputation due to necrosis and ulcer lesion following a burn injury to the first toes and severe ischemic peripheral vascular disease. In a sitting position with the base of the foot of the non-amputated left leg on the ground, he performed repeat knee extension of the resected stump (knee active extension and passive flexion without a target KROM) for 1 min with both self-controlled free KER and different target KERs (30, 40, 50, 60, and 80 contractions per minute [cpm] using a metronome), with or without a 0.5 kg weight placed on the resected stump over 8 consecutive days. The KROM was measured using a goniometer placed between the resected stump and the thigh muscle with a continuous data acquisition system. The mean values achieved for KER, KROM, and angle rate during a 1 min session was determined during each daily session, and consecutively average values over sessions on 8 consecutive days was also evaluated. The achieved mean KER at all target KERs corresponded closely with the target KER. The average KROM was approximately 60 degrees over a range of targets between 30 and 60 cpm, but the value was lower at approximately 50 degrees at 80 cpm. The angle rate increased consistently with the increase from a target of 30 to 60 cpm, but it was reduced at 80 cpm. The mean KROM was inversely related (r=-0.390, P<0.01, n=40) to the mean KER without the weight, but not significantly (r=-0.256, P=ns, n=40) with the 0.5 kg weight. The achieved KER in the self-controlled free trial with or without the 0.5 kg weight might increase with an increase in sessions over 8 days with a range between approximately 30 and 60 cpm. Conclusion: The present case study showed that a higher contraction frequency may limit KROM determined below 60 cpm because of the reduced angle rate in an amputated lower leg. A low and moderate KER below 60 cpm may be appropriate to maintain KROM with a stable angle rate. Furthermore, voluntary KER with free self-controlled rhythm may increase over the course of multiple sessions as familiarity improves with kicking the amputated limb and generating a potential improvement in performance/ability effect with consecutive leg exercise with no use of a prothesis such as in the early/acute phase post-amputation using audible biofeedback.

Mortality after implantable cardioverter defibrillators in dialysis patients: a nationwide study

Abstract Background Although randomized clinical trials have shown that implantable cardioverter defibrillators (ICDs) reduce mortality in selected patients, patients on dialysis are excluded from these trials. Thus, data on mortality risk after ICD implantation in these patients are sparse. Purpose To examine all-cause mortality in patients receiving an ICD according to dialysis status and to identify factors associated with all-cause mortality in patients on dialysis. Methods Using Danish nationwide registries from 2000–2017, all patients ≥18 years old undergoing first-time ICD implantation were included. Patients on dialysis were identified prior to ICD implantation and followed for up to five years. The cumulative incidence of all-cause mortality according to dialysis status was assessed. Factors associated with all-cause mortality after ICD implantation in dialysis patients were examined using multivariable Cox proportional hazard regression. Results A total of 14,681 ICD patients were identified, of which 218 (1.5%) were on dialysis prior to ICD implantation. Compared with ICD patients not on dialysis, those on dialysis were younger (median age 64 years [IQR: 58–70] vs. 66 years [IQR: 57–72], p=0.02), more likely to receive an ICD for secondary prophylaxis (69.7% vs 53.7%), and had more comorbidities including ischaemic heart disease (60.6% vs. 46.3%), diabetes (28.4% vs. 20.4%), and peripheral vascular disease (10.1% vs. 5.6%) (p for all <0.05). The median time to death among ICD patients on dialysis and not on dialysis were 1.3 years (IQR: 0.4–2.8 years] and 2.2 years [IQR: 1.0–3.5 years], respectively. One-year mortality among ICD patients on dialysis (13.0%) was significantly higher compared with ICD patients not on dialysis (4.7%), p<0.001 (Figure). Five-year mortality was significantly higher in ICD patients on dialysis than those not on dialysis (42.2% vs 23.6%), p<0.001 (Figure). Factors associated with increased risk of all-cause mortality among ICD patients on dialysis were age ≥65 years at time of implantation (reference: age <65 years) (HR 1.90 [95% CI: 1.13–3.19]), primary prophylactic ICD (HR 1.81 [95% CI 1.08–3.05]), and diabetes (HR 1.87 [95% CI 1.14–3.07]). Sex, ischaemic heart disease, heart failure, stroke, chronic obstructive pulmonary disease, and malignancy were not associated with the risk of mortality (p>0.05 for all). Cardiovascular causes of death were common both in patients with- and without dialysis, 69.6% and 60.0%, respectively. Conclusion Five-year mortality in ICD patients on dialysis was 42% and twice as high compared with ICD patients not on dialysis. Age ≥65 years, primary prophylactic indication, and diabetes were factors associated with increased mortality. Careful evaluation of the potential benefit from an ICD implantation in dialysis patients is important considering the overall high mortality rates. Funding Acknowledgement Type of funding source: None

P0580ACUTE INTERSTITIAL NEPHRITIS RELATED TO EMPAGLIFLOZIN

Abstract Background and Aims SGLT-2 inhibitors are effective anti-hyperglycemic agents with proved cardiovascular and renal benefits. However, there have been post marketing reports of episodes of acute kidney injury (AKI), some requiring hospitalization and even dialysis in patients receiving SGLT2 inhibitors. This phenomenon may be related to volume contraction and hemodynamic changes, particularly in patients with other risk factors (such as patients on RAAS blocking agents or NSAIDS, patients with CKD). We present a case of acute interstitial nephritis (AIN) and acute tubular necrosis related to an SGLT2-inhibitor. Method Case report description. Results A 67-year-old women was admitted with weakness, dizziness and abdominal pain. Her medical history was remarkable for hypertension, diabetes mellitus, ischemic heart disease and peripheral vascular disease. Her medications included bisoprolol, losartan, amlodipine, sitagliptin and aspirin. Two months prior the current presentation, empagliflozin was prescribed by her primary physician for her diabetes mellitus. However, several days after initiation of empgliflozin she felt weak and dizzy and empagliflozin was discontinued. A week before the current presentation, empagliflozin was re-initiated by her cardiologist. The patient reported no recent illness, fevers, rash, arthralgias, respiratory symptoms or bone pain. She denied exposure to other new medications (including NSAIDS and antibiotics). On admission, blood pressure was 165/76 mm Hg. The rest of the physical examination was unremarkable. Laboratory studies revealed acute kidney injury (creatinine 3.19 mg/dL, BUN 28 mg/dL, baseline creatinine 0.9 mg/dL). Complete blood count demonstrated no eosinophilia or thrombocytopenia. Urinalysis showed a few leukocytes but no red cells or casts. The urine protein to creatinine ratio was 5160 mg of protein per gram creatinine. Abdominal ultrasonography showed normal-size kidneys and no hydronephrosis. Immunologic and infectious serologies were unremarkable. over several days the patient became oligo-anuric and creatinine peaked to 9.22 mg/dL and hemodialysis was initiated. Empiric treatment with prednisone was given and a renal biopsy was performed. Four glomeruli were seen on light microscopy. The glomeruli were normocellular. An interstitial infiltrate of lymphocytes and small numbers of eosinophils were seen. Thining of the renal tubular brush border with intra-tubular necrotic content was a also seen. Immunofluorescence was negative. The findings were compatible with acute interstitial nephritis and acute tubular necrosis (Figure 1). The patient was discharged with a regimen of intermittent hemodialysis and steroid therapy. Three months later, urine output and kidney function improved, and the patient was weaned off dialysis. Conclusion In this case report, we describe previously unreported histologically proven AIN likely related to empagliflozin exposure. Although SGLT2 inhibitors have been reported to be associated with AKI it has been supposed to be related to volume contraction and hemodynamic changes. As virtually any drug can cause AIN, further proof of the drug's causation in our case was an onset of renal dysfunction with re- institution of empagliflozin, biopsy-proven AIN and absence of other drugs, infection or systemic disease that might cause AIN. With the dramatic increase in use of SGLT-2 inhibitors worldwide, treating physicians should be aware of AIN as a possible cause of AKI in this context.

P1527SURVIVAL COMPARISON:HEMODIALYSIS VS PERITONEAL DIALYSIS: TEN YEARS OBSERVATIONAL STUDY

Abstract Background and Aims Survival comparison between peritoneal dialysis (PD) and hemodialysis (HD) is still controversial. While some retrospective studies have shown better survival in PD, particularly in the first year, others have not identified this difference. The only RCT published so far showed a 3-year mortality rate similar between two groups. However, the number of patients was too small to provide sufficient statistical power to identify any survival differences between the two dialysis techniques. Aim of this study was to compare HD and PD in term of survival rate and factors possibly involved in a ten-years observational study. Method We retrospectively evaluated all the incident patients that started a dialytic treatment, either HD or PD, due to uremia from 01-01-2008 to 31-12-2018 at the U.O. Nephrology ASST Spedali Civili of Brescia. Exclusion criteria were: duration of dialysis treatment less than 3 months, and previous dialytic treatment or kidney transplantation. For each patient anthropometric, clinical-anamnestic data and comorbidities at dialysis start were recorded. Results One thousand and six patients were identified. 130 patients were excluded due to dialysis treatment less than 3 months. A total 876 patients were analyzed. 77% of patients started dialysis on HD while 23% chose PD. Age was significantly higher in HD patients (69±15 vs 65±16 years; p<0.05). No differences were found in the incidence of: ischemic heart disease (HD 24%, PD 25%, p=0.90), diabetes (32% vs 32%, p=0.83), cancer (20% vs 17%, p=0.37), cardiac arrhythmia (20% vs 25%, p=0.08) and peripheral vascular disease (25% vs 25%, p=0.89). An increased incidence of COPD (HD 17% vs PD 8%, p<0.05) and hypertension (73% vs 87%, p<0.05) was present in PD patients. During follow-up, 17% of patients treated with PD shifted to HD due to catheter malfunction, recurrent infections, insufficient dialytic adequacy or ultrafiltration failure. Kidney transplants were performed more frequently in PD patients (HD 12%; PD 24%, p<0.05). At an intention to treat analysis of the data, univariate analysis showed better survival in PD patients (p<0.05, Figure 1). This difference was not confirmed at multivariate analysis (Figure 2), where age, cardiac arrhythmia, cirrhosis, diabetes and peripheral vascular disease were independently associated with an increased risk of mortality. No independent influence on mortality of the dialysis treatment modality was found. Conclusion This ten years observational study shows that HD and PD are similar in term of patient survival. Age and comorbidities seem to play the most important role in patient survival.

P2468Clinical and cardiac structural differences between paroxysmal and persistent/permanent non-valvular atrial fibrillation

Abstract Background Atrial Fibrillation (AF) is a heterogeneous condition and is traditionally classified by duration (paroxysmal, persistent and permanent). There is a relationship between AF and left atrial (LA) remodeling, with increased likelihood of AF recurrence and maintenance with increasing LA volumes. Purpose To assess clinical and cardiac structural differences between the subtypes of AF. Methods We examined 1247 (68±13.4y; 50% men) consecutive admissions presenting to our institution with the primary diagnosis of AF. Repeat admissions (n=263) were excluded. Of remaining 984 subjects, a majority had diagnosed paroxysmal (72.2%), with lower numbers of persistent (23.4%) and permanent (4.4%) AF. Echo parameters of cardiac chamber size and function were examined in a subset of subjects with complete echo (n=646) performed during incident hospital admission. Results There were significantly higher rates of diabetes mellitus (p=0.03), ischaemic heart disease (IHD; p=0.04) and peripheral vascular disease (PVD; p=0.02) in those with persistent/permanent AF compared to paroxysmal AF. No significant differences in age (p=0.19), BMI (p=0.42), OSA (p=0.05), or hypertension (p=0.76) was noted. There were significant differences in left ventricular (LV) mass and systolic function, LA size and function between the two groups (Table 1). Receiver operator curve analysis revealed that LAEF was a discriminator for persistent/permanent AF with an area under the curve of 0.689 (95% CI, 0.646 to 0.732; p<0.001). Echo parameters in AF subtype Echocardiographic Parameters Paroxysmal AF (n=433) Persistent and Permanent AF (n=213) Significance (p value) LVEDD (cm) 4.8±3.0 5.0±0.9 0.29 LVESD (cm) 3.3±1.3 3.7±1.1 <0.01 IVS thickness (cm) 1.2±0.7 1.1±0.3 0.44 PW thickness (cm) 1.1±0.7 1.1±0.2 0.77 LV mass (g) 92.3±28.3 108.2±35.3 <0.01 LVEF (%) 56.1±14.1 47.4±16.8 <0.01 LA Expansion Index 89.4±69.1 53.4±40.3 <0.01 Min LA Volume indexed (ml/m2) 18.9±17.2 27.3±20.6 0.01 Max LA Volume indexed (ml/m2) 32.5±19.2 37.7±15.3 <0.01 LAEF (%) 41.8±16.4 31.5±13.6 <0.01 Conclusions Our results suggest diabetes, IHD and PVD are associated with persistent/permanent AF. Additionally, greater LA remodeling and reduced atrial function was noted in this group, suggestive of an association between duration of AF electrical burden and LA remodeling and function.

Abstract WP393: Usage of Emergency Medical Services Among Ischemic Stroke Patients: Data From China Stroke Center Alliance

Background and Purpose: Emergency medical services (EMSs) is critical for the early treatment of ischemic stroke patients, yet data regarding EMSs utilization and its association with timely treatment are still limited in China. Methods: We examined the data from Chinese Stroke Center Alliance (CSCA) recording consecutive ischemic stroke patients from 2015 June to 2017 November. The absolute standardized difference was used for covariates balance assessments. We used multivariable logistic models to identify factors associated with EMSs usage and to evaluate the effect of EMSs on timely treatment. Results: Of the 326,534 analyzed ischemic patients, only 42,293 (13.0%) were transported by EMSs. Multivariable-adjusted results indicated that younger age, less education, non-urban employ medial insurance, lower income level, less stroke severity, smoking, history of stroke/transient ischemic attack, carotid stenosis, hypertension, diabetes and peripheral vascular disease were associated with decreased risk of EMSs usage. However, coronary heart disease or myocardial infarction, atrial fibrillation and heart failure were associated with increased risk of EMSs usage. Compared to self-transportation, EMS-transported patients were associated with significantly shorter onset-to-door time (Median (IQR): 210 (105-586) vs. 1020 (290-2250) minutes, P<0.0001), higher chance of arrival at hospitals within 2 hours (32.0% vs 9.4%, OR=3.77, 95% CI: 3.53-4.02) or within 3.5 hours (50.1% vs 19.0%, OR=3.60, 95% CI, 3.35-3.86) after symptom onset, and treated with IV tPA (13.8% vs 3.6%, OR=3.06, 95% CI:2.75-3.41). Conclusions: EMSs utilization is far from optimal among Chinse ischemic stroke patients. Nevertheless, use of EMSs transportation is associated with substantial reductions in prehospital delay and improved chance of timely treatment. Therefore, community education efforts are needed to improve EMSs activation.

Ager Deletion Enhances Ischemic Muscle Inflammation, Angiogenesis, and Blood Flow Recovery in Diabetic Mice.

Diabetic subjects are at higher risk of ischemic peripheral vascular disease. We tested the hypothesis that advanced glycation end products (AGEs) and their receptor (RAGE) block angiogenesis and blood flow recovery after hindlimb ischemia induced by femoral artery ligation through modulation of immune/inflammatory mechanisms. Wild-type mice rendered diabetic with streptozotocin and subjected to unilateral femoral artery ligation displayed increased accumulation and expression of AGEs and RAGE in ischemic muscle. In diabetic wild-type mice, femoral artery ligation attenuated angiogenesis and impaired blood flow recovery, in parallel with reduced macrophage content in ischemic muscle and suppression of early inflammatory gene expression, including Ccl2 (chemokine [C-C motif] ligand-2) and Egr1 (early growth response gene-1) versus nondiabetic mice. Deletion of Ager (gene encoding RAGE) or transgenic expression of Glo1 (reduces AGEs) restored adaptive inflammation, angiogenesis, and blood flow recovery in diabetic mice. In diabetes mellitus, deletion of Ager increased circulating Ly6Chi monocytes and augmented macrophage infiltration into ischemic muscle tissue after femoral artery ligation. In vitro, macrophages grown in high glucose display inflammation that is skewed to expression of tissue damage versus tissue repair gene expression. Further, macrophages grown in high versus low glucose demonstrate blunted macrophage-endothelial cell interactions. In both settings, these adverse effects of high glucose were reversed by Ager deletion in macrophages. These findings indicate that RAGE attenuates adaptive inflammation in hindlimb ischemia; underscore microenvironment-specific functions for RAGE in inflammation in tissue repair versus damage; and illustrate that AGE/RAGE antagonism may fill a critical gap in diabetic peripheral vascular disease.

Limitations of spinal cord stimulation for pain management.

Limitations of spinal cord stimulation for pain management.

IMPAIRED ENDOTHELIAL NITRIC OXIDE IS COMPENSATED BY EDHF IN RESISTANCE ARTERIES FROM SUBJECTS WITH PERIPHERAL VASCULAR DISEASE

Peripheral vascular disease is associated with altered blood flow dynamics and microvascular function. The vascular endothelium is a significant contributor to cardiovascular health and microvascular tone via the release of known endothelium-derived relaxing factors. The aim of this study was to examine endothelium-dependent and endothelium-independent function in small resistance arteries in an attempt to identify potential mechanism underlying lower limb ischaemia. Resistance arteries were isolated from 26 male subjects with ischaemic peripheral vascular disease. Skeletal muscle biopsies were taken from proximal skeletal muscle (PSM) non-ischaemic and distal skeletal muscle (DSM) ischaemic sites and structure and function compared. Significant endothelium-dependent dysfunction was observed in DSM resistance arteries when compared with PSM. Endothelial dysfunction appears exclusive to loss of endothelium-derived nitric oxide whereas endothelium-derived hyperpolarizing factor type mediated relaxation appears to be up regulated. The loss of endothelium-dependent phosphorylation of eNOS was correlated with increased expression of the negative regulator caveolin-1. Expression of total eNOS and heat shock protein 90 were unaffected. These data provide novel insight into the mechanism underlying significant loss of endothelial vascular homeostatic control mechanisms in human resistance arteries. This study provides further understanding of vascular pathogenesis in peripheral vascular disease highlighting the pathological adaptation and restorative compensatory mechanism of the endothelium in resistance arteries.

SAT0300 Microcirculation and Macrovascular Disease in Systemic Sclerosis – A Nailfold Capillary Study

BackgroundEmerging evidence demonstrate that patients with systemic sclerosis (SSc) suffer from both micro- and macrovascular disease. Structural changes in nailfold capillaries, a marker of microvascular involvement, has been associated with...

Apolipoprotein (a) Impairs Endothelial Progenitor Cell-Mediated Angiogenesis

Improvement of blood flow and promotion of angiogenesis are important therapeutic measures for the treatment of ischemic peripheral vascular diseases. Since apolipoprotein (a) (apo (a)) is a glycoprotein with repetitive kringle domains exhibiting 75% to 98% structural homology with plasminogen (Plg), apo (a) may also have a negative effect on endothelial progenitor cell (EPC)-induced angiogenesis through Plg-like inhibitory effects on EPC proliferation, adhesion, migration, and angiogenesis. To evaluate the effect of apo (a) on EPCs-induced angiogenesis, EPCs were isolated from the bone marrow of apo (a) transgenic mice, wild-type litter mates, and normal mice. These cells were cultured without or with apo (a) before transplantation. Hindlimb ischemia models were surgically induced in mice, which then received an intravenous injection of 3×10(5) EPCs. At 3, 7, and 14 days post EPC transplantation, the adhesion, migration abilities, and capillary density in calf muscles were assessed. Results indicate that apo (a) significantly reduced the adhesion and migration abilities of EPCs. Furthermore, the tubule-like formation of EPCs on Matrigel gels was damaged. In vivo experiments showed the homing of EPCs to ischemic peripheral vascular, and the number of capillary vessels decreased significantly in apo(a) transgenic mice. This study demonstrated that apo (a) could attenuate the adhesion, migration, and homing abilities of EPCs and could impair the angiogenesis ability of EPCs.

Ischemic arterial events and atherosclerosis in patients with systemic sclerosis: a population-based case-control study

IntroductionWhile microvascular disease is well described in systemic sclerosis (SSc), it is still unclear whether the occurrence of ischemic macrovascular events and atherosclerosis is enhanced among patients with SSc.MethodsIn this study, 111 SSc patients (74% of prevalent cases in Stockholm County) and 105 age- and sex-comparable population controls were investigated. Previous ischemic arterial events were tabulated. As surrogate measures of atherosclerosis, plaque occurrence and intima-media thickness (IMT) were determined with carotid ultrasound and the ankle-brachial index (ABI) was calculated. Traditional cardiovascular risk factors were recorded and we also measured biomarkers indicating systemic inflammation and endothelial activation/dysfunction.ResultsMean age was 62 ± 12 years for patients and controls. Ischemic arterial events were more common, due to increased occurrence of ischemic heart disease (IHD) and ischemic peripheral vascular disease (IPVD), in the patient group (12% vs. 4%, P = 0.03 and 9% vs. 0%, P = 0.003 respectively). On a group level, there was no difference regarding the occurrence of ischemic cerebrovascular disease, the frequency of plaques, IMT or ABI between SSc patients and controls. Subgroup analyses revealed that patients with anticentromere antibodies (ACA+) had more plaques and more ischemic arterial events compared to other SSc patients (67% vs. 39% and 32% vs. 11%; P = 0.006 and P = 0.01, respectively) and compared to controls (67% vs. 41% and 32% vs. 7%, P = 0.02 and P = 0.0003, respectively). Biomarkers of inflammation/endothelial activation were generally increased among SSc patients.ConclusionsPatients with SSc are at enhanced risk for IHD and IPVD. The ACA+ SSc subgroup was particularly affected with both ischemic arterial events and premature atherosclerosis. The microvascular vulnerability of ACA+ patients is previously well documented. We demonstrate that ACA+ SSc patients have an enhanced risk of macrovascular injury as well. This group should be followed closely and modifiable cardiovascular risk factors should be treated at an early stage.

Spinal cord stimulation: panacea for incurable diseases?

A spinal cord stimulator is usually used as an electro-modulator for pain treatment. Shealy et al. [1] first reported the use of a spinal cord stimulator in an elderly male suffering with terminal bronchogenic carcinoma and right-sided chest pain in 1967. Since then, spinal cord stimulation (SCS) has been applied to many disease entities, such as neuropathic pain, failed back surgery syndrome, complex regional pain syndrome, and ischemic peripheral vascular disease [2-4]. The indications for SCS have been extended to include intractable angina pain, interstitial cystitis, intractable pain, headache, and non-painrelated applications such as refractory congestive heart failure, intractable spasticity, or treatment of cerebral vasospasm after subarachnoid hemorrhage [5-9]. SCS systems are composed of three components: leads/electrodes, a generator/power source, and a programmer/controller [5]. Leads can be divided into percutaneous leads and paddle leads. Small-sized rechargeable implanted batteries are becoming increasingly common. An electrical current is applied to the dorsal columns, creating a tingling sensation in the dermatomes whose afferent fibers traverse the regions being stimulated. The physician can control the degree, range of current, pulse width, and rate of the stimulation wave to optimize pain control. In this issue of the Korean Journal of Anesthesiology, Ryu et al. [10] report the effect of cervical SCS for treatment of digit ulcers in a patient with Buerger’s disease. Thromboangiitis obliterans is a type of segmental inflammatory vasculitis asso ciated with severe pain and ulcers, which involves the small or medium-sized arteries and veins. Treatment of this painful ulcer is difficult and often involves amputation of the affected limb. This case report suggests that cervical SCS is a good choice for reducing pain and healing of an ulcer in patients with vasculitis. There are some reports of the effectiveness of SCS for patients with Raynaud’s disease and Buerger’s disease [11-13]. Cook et al. [14] reported using electronic stimulation of spinal nerves and the dorsal root in patients with a vascular disease of the limbs. Since then, SCS has been successfully used to treat atherosclerotic and vasospastic peripheral arterial disease. SCS improves microcirculation by inhibiting sympathetic vasoconstriction. SCS reduces pain in Buerger’s disease by stimulating the secretion of a number of inhibitory neurotransmitters and promoting the secretion of gamma aminobutyric acid, substance P, and serotonin at the spinal nerve dorsal horn [15,16]. Wolter and Kieselbach [17] reported the long-term outcomes of patients with cervical SCS. Treatment indications included patients with causalgia, cervicobrachialgia, complex regional pain syndrome, phantom pain, and Raynaud’s syndrome [18]. Pain reduction and paresthesia coverage were effective in almost all patients, and treatment satisfaction was high. No severe complications, such as neurological deficits or infection, were reported. They concluded that cervical SCS appears to be a safe and efficacious treatment option for upper limb neuropathic pain. Nevertheless, SCS has some disadvantages. The procedure for implanting SCS is invasive, so it is associated with complications such as infection, bleeding, and dural puncture [19]. The effectiveness of SCS is limited, and regular checks and continuous follow-ups are needed. Furthermore, SCS is expensive because of the limited medical insurance coverage in Korea. However, SCS is cost effective as compared with conservative management alone in cases with medical insurance coverage. Advances in SCS technology and understanding of the

Journal Club

Journal Club

Abstract P246: A Naturalistic Assessment of Lipid Treatment Strategies: Further LDL-C Reduction Versus Comprehensive Lipid Management

Objective: To compare cardiovascular (CV) outcomes between patients initiating adjunct therapy with either niacin extended-release (NER) for broader lipid panel management or ezetimibe (EZE) for continued LDL-C reduction. Methods: Statin-treated patients aged ≥30 augmenting with NER or EZE between 1/1/05-11/30/09 (Index Date) were identified. Patients with ≥12 months of health plan eligibility before the Index Date (baseline) were included, and patients with secondary risk and ≥1 full lipid panel were retained. A propensity score (PPS) model was developed controlling for the following baseline factors: age, gender, geographic region, type of health coverage, baseline lipids, mode of therapy augmentation, potency of adjunct statin therapy, baseline statin adherence, comorbidities, and alternative CV medications. NER and EZE patients were matched based on PPS. Clinical outcomes included incidence of a major adverse cardiovascular event (MACE). MACE was defined as a composite of acute ischemic heart (IHD), peripheral vascular (PVD), and cerebrovascular disease (CVD) events. The economic outcome was annual CV disease-related costs. These outcomes were compared using univariate Cox proportional hazards and generalized linear models respectively. Results: A total of 15,195 patients initiated adjunct therapy with NER (n=3,098) and EZE (n=12,097) meeting all study criteria. Post-PPS match, 2,261 patients were identified in each cohort with no statistically significant differences in baseline or concurrent treatment characteristics. Frequency of MACE was lower among NER patients (3.5%) vs. EZE (5.4%), with a hazard ratio (HR) of 0.89 (95% CI: 0.67-1.20). Specifically, NER patients demonstrated a lower risk of IHD (HR: 0.90; 95% CI: 0.65-1.25) and CVD (HR: 0.69; 95% CI: 0.34-1.41) events vs. EZE patients. These findings correspond to significantly lower adjusted annual cost among NER patients ($8,168; 95% CI: $7,720 - $8,641) vs. EZE ($9,030; 95% CI: $8,535 - $9,553) ( P= 0.0136). Conclusions: Positive clinical benefits observed in this broader naturalistic population are consistent with results from recent clinical trials and suggest that treating beyond LDL-C with statin + NER in secondary risk patients may reduce CV risk and associated costs.

A systematic review of the effectiveness of preventive measures for coronary artery disease in Asian Indians.

Review Question/Objectives The objective of this systematic review is to examine the best available evidence regarding prevention of coronary artery disease (CAD) in Asian Indians (AI). The anticipated outcome is an evidence based practice recommendation that maximizes preventive strategies in AI. Specifically, the review seeks answers to the following questions: 1. What strategies are most effective in the early detection of CAD in this population? 2. What are the most effective primary prevention strategies for CAD in Asian Indians? 3. What are the most effective secondary prevention strategies for CAD in Asian Indians? Types of Participants The review will consider studies that include Asian Indians who are healthy or may be at risk of developing CAD (primary prevention) and those who have CAD (secondary prevention). For this review “Asian Indians” will include people who trace their origin to the country of India. The participants to be studied are both AI male and female adults, 18 years or older. Studies with a primary focus only on participants from other countries in South Asia (Pakistan, Bangladesh and Srilanka) other than India would be excluded. Studies on AI children would not be included for this review. Types of Interventions/Phenomenon of interest The review will consider studies that evaluate the strategies for early detection of CAD and instituting prevention strategies in AI. Both primary and secondary preventive measures will be considered for review. For this review the primary prevention strategies will consider prevention measures for apparently healthy AI with no CAD. The secondary prevention strategies will consider prevention measures for AI who have CAD.Screening for risk factors (early detection), lifestyle modifications, and pharmacological therapy for prevention will be considered for this review. Studies on AIs with ischemic heart disease, angina and myocardial infarction will be included. Any interventions and treatments of CAD other than prevention will be excluded. Preventive revascularization measures such as percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) will be excluded. Studies on cerebrovascular disease such as stroke, transient ischemic attack (TIA) and peripheral vascular disease (PVD) will be excluded. TRUNCATED AT 350 WORDS

To Determine the Patterns of Dyslipidaemia Amongst the Macrovascular Complications of Type – II Diabetes Mellitus

Objective: To assess the characteristics of dyslipidaemia amongst the type 2 diabetic patient with macrovascular compli-cations like ischaemic heart disease, cerebrovascular and peripheral vascular disease and to compare the variables of dyslipidemia in male and female subjects under study. Design: A prospective observational analytic study. Setting and place of Study: Study was conducted in medical unit-III of Bahawal Victoria Hospital Bahawalpur, over a period of 6 months from 1st July, 2008 to 31st December, 2008. Procedure: A total of hundred patients of type 2 diabetes were randomly selected for study. Those who had hyperlipidaemia due to secondary causes e.x. nephrotic syndrome, drugs, hypothyroidism etc. were excluded. Blood samples were taken for serum sugar fasting and random and fasting lipid profile. For statistical analysis student t.test at 5% level of significance was used. All mean values were presented as mean ± SD (Standard Deviation). Results: Majority of patients presented in middle and old age category, and they had poor glycemic control. The female patients had uncontrolled hyperglycemic and hypertensive (BP = 145 ± 25.72 / 85.6 ± 76 mm/Hg) than males and their mean random serum sugar was 246.64 ± 105 mg% High percentage of complications were observed in patients of middle age group with great frequency of cardiovascular complications like coronary heart diseases and hypertension (52%) followed by cerebrovascular complications (30%) and peripheral vascular disease (18%). The lipid profile was in high risk range in pati-ents with cardiovascular and cerebrovascular complications. In patients with CHD, the mean +SD concentration of choles-terol was 207.08 ± 27.94 mg/dl, HDL – C was 34.8 ± 6.27 mg/dl and TC : HDLC ratio > 6, (normally TC:HDLC ratio should be 40 mg/dl). In patients with CVA, HDL – C was 35.09 ± 6 mg/dl and triglycerides was 146.9 ± 50.70 mg/dl and these variables meet the definition of isolated low HDL – C (defined as TG < 150 mg% and HDL – C < 35 mg% = isolated low HDL – C) and that was considered as independent risk factor. LDL – C concentration was high normal (188 ± 23.4 mg/dl) in these cases. Collectively the mean concentration of LDL-C was raised and statistically very highly significant in all these macrovascular complications. In female patients, the mean concentration of LDL – C, triglycerides and HDL – C was 191 ± 31.6 mg/dl, 179 ± 93 mg/dl and 32 ± 2.4 mg/dl respectively, all in high risk range. Conclusion: Poor glycemic control is associated with higher incidence of dyslipidaemia in type 2 diabetes. Current study confirms the association of hypercholesterolemia, low HDL-C and increased TC HDL-C ratio (all in high risk range) in patients with coronary heart disease, hypertension and CVA. Lipid profile was found to be significantly higher among females. Key Words: Diabetic dyslipidaemia HDL – C. LDL – C. Triglycerides. Macrovascular complications.