Search Results (48)

Background/Objectives: Although hypertension is linked to oxidative stress, it remains unclear whether this pro-oxidant state persists after achieving recommended blood pressure (BP) control. This pilot study aimed to explore the presence of residual oxidative stress in patients with well-controlled hypertension compared to normotensive individuals. Methods: In this cross-sectional pilot study, 34 adults were enrolled: 20 normotensive controls and 14 patients with well-controlled hypertension (office BP < 140/90 mmHg). Macrovascular status was assessed by ankle–brachial index (ABI), and plasma concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured. Hypertensive patients were further stratified by median MDA levels for subgroup analysis. Results: Baseline characteristics, including BP, were similar between groups. However, patients with well-controlled hypertension exhibited significantly higher plasma MDA concentrations compared to normotensive controls (9.91 ± 6.07 vs. 4.73 ± 2.34 µmol/L, p = 0.008). In subgroup analysis, hypertensive patients with high MDA were significantly older (p = 0.03) and showed a trend towards higher systolic BP (p = 0.05) compared to those with low MDA. No significant differences were observed in SOD or catalase activity, ABI, or inflammatory markers (all p > 0.05). Conclusions: Residual oxidative stress—as reflected by increased plasma MDA—persists in patients with well-controlled hypertension. While this oxidative state appears broadly independent of BP when viewed as a whole, it is notably more pronounced in older patients and in those with systolic BP approaching the upper limit of the controlled range. These findings support the need for comprehensive, biomarker-based risk assessment and further investigation into targeted strategies for mitigating persistent redox imbalance in hypertension. Full article

Background/Objectives: Cardiovascular diseases remain the leading cause of death among women, with peripheral arterial disease (PAD) representing an important manifestation of systemic atherosclerosis. The ankle–brachial index (ABI) is a simple, non-invasive measure used for PAD screening and cardiovascular risk assessment. This study aimed to compare ABI values between women of reproductive and postmenopausal age and to explore associations with lifestyle and clinical characteristics in primary care settings. Methods: This cross-sectional study included 437 women recruited from family medicine offices in two Croatian counties between November and December 2024. Participants completed validated questionnaires on dietary habits (MEDAS) and physical activity (IPAQ/PASE), and underwent anthropometric and blood pressure measurements. ABI was assessed using an automated MESI device following a standardized protocol. Multivariable logistic regression was performed to identify independent predictors of abnormal ABI (<1.00), adjusting for age, BMI, hypertension, smoking, and county. Results: Most participants had normal ABI values (right 95.7%; left 95.0%). Mild to moderate PAD (ABI 0.90–0.99) was observed in approximately 3% and severe PAD (ABI < 0.90) in ≤1.1% of cases. Postmenopausal women were more likely to present with lower ABI values (p = 0.046), though this association was attenuated after adjusting for age. Lifestyle factors, including diet and physical activity, showed no significant association with ABI in the adjusted models. Conclusions: Age emerged as the primary determinant of reduced ABI, while hypertension and smoking showed positive but non-significant associations. The findings underscore the importance of early vascular screening and lifestyle-based prevention in women, particularly in the postmenopausal period. Larger longitudinal studies are warranted to clarify causal pathways and the role of hormonal and behavioral factors in peripheral arterial disease development. Full article

In the current study, we focus on analyzing the relationship between changes in micro- and macrocirculation and different stages of metabolic memory. We hypothesized that early poor glycemic control induces lasting endothelial changes detectable in pediatric type 1 diabetes (T1D) microcirculation. We assessed microcirculation structure and function using capillaroscopy, transcutaneous oxygen pressure (TcPO₂), and optical coherence tomography (OCT). We evaluated macrovascular circulation using pulsatility index (PI), ankle-brachial index (ABI) and pulse pressure (PP). We also examined the relationship between circulation parameters, the age at onset, and diabetes duration. The study included 67 patients with uncomplicated type 1. We divided all patients into four groups based on their HbA_1c levels at T1D onset and their average HbA_1c after one and two years. We assessed the concentrations of TNF-α, IL-35, IL-4, IL-10, IL-18, IL-12, serum angiogenin, VEGF, sVCAM-1, ICAM-1, sP-Selectin, AGEs, and sRAGE. We compared subgroups with different levels of metabolic memory but comparable T1D duration and age at diagnosis. Micro- and macrovascular parameters were similar between the groups. Our comparison of subgroups with identical metabolic memory but different durations and ages at diagnosis revealed clear differences. The subgroup with a shorter T1D duration showed higher capillary density and a smaller inter-capillary distance compared to those with a longer diabetes duration. This subgroup with shorter duration had significantly lower AGE levels and a reduced TNF-α/IL-35 ratio, along with higher levels of IL-35, IL-4, and IL-12, compared to the longer-duration group. Our findings indicate that in youths with uncomplicated T1D, disease duration—not metabolic memory—plays a dominant role in early microvascular alterations. Full article

Background: High-sensitivity cardiac troponin T serum concentration (hs-cTnT) measurement is a well-established tool in the diagnosis of acute cardiovascular (CV) disease. It remains unclear whether resting hs-cTnT could be useful for screening the status of the CV system. The purpose of this study was to compare the correlation between hs-cTnT, determined in patients without clinical symptoms of acute illness, and selected parameters of subclinical CV dysfunction in relation to the coexistence of arterial hypertension (AH). Methods: In total, 101 patients were included in the analysis. The following methods were used to assess the CV system: transthoracic echocardiography, Doppler ultrasonography of the carotid and lower extremity arteries with intima–media thickness (IMT) measurement, pulse wave velocity (PWV), central blood pressure measurement, ankle–brachial index (ABI), and toe–brachial index (TBI). Results: In patients with AH, significant correlations were found between hs-cTnT and maximal velocity of tricuspid regurgitation (R = 0.397; p = 0.003), left atrium volume index (LAVI) (R = 0.39; p = 0.002), and IMT in carotid arteries (cIMT) (R = 0.4; p = 0.001), common femoral arteries (cfIMT) (R = 0.384; p = 0.004), and superficial femoral arteries (sfIMT) (R = 0.352; p = 0.01), as well as PWV (R = 0.63; p < 0.001), central systolic blood pressure (cSBP) (R = 0.34; p = 0.006), central pulse pressure (cPP) (R = 0.354; p = 0.004), and ankle–brachial index (ABI) (R = −0.28; p = 0.024). In multivariate analysis, the relationship between subclinical CV dysfunction and hs-cTnT remained significant for LAVI, cSBP, cPP, and ABI, as well as showing borderline significance for sfIMT. In patients without AH, only the relationship between hs-cTnT and ABI was significant. According to interaction analysis, AH significantly influenced the relationship between hs-cTnT and cSBP, cPP, and sfIMT. Conclusions: Resting hs-cTnT correlates significantly with selected parameters of subclinical CV dysfunction in patients with AH. This relationship is clearly weaker in patients without AH. Further research is needed, especially prospective studies on a larger group of patients. Full article

Background/Objectives: The ankle-brachial index (ABI) is a non-invasive diagnostic tool for peripheral artery disease (PAD) and a marker of systemic atherosclerosis, predictive of cardiovascular (CV) events. The ambulatory arterial stiffness index (AASI), derived from 24-h blood pressure monitoring, also predicts CV morbidity and mortality, particularly stroke. However, their combined prognostic utility in acute myocardial infarction (AMI) remains underexplored. This study aimed to assess the predictive value of ABI and AASI in patients with AMI. Methods: We conducted a single-center observational cohort study including 441 consecutive patients with AMI (79% male; mean age 62 years). ABI was measured using an automated device, with ≤0.9 defined as abnormal. AASI was calculated from 24-h blood pressure recordings. The primary endpoint was a composite of all-cause and CV death and major CV events, assessed in-hospital and over a 3-year follow-up. Results: Median ABI was 1.10 (IQR 1.00–1.18); 10.4% had abnormal ABI. Abnormal ABI was associated with a threefold higher risk of in-hospital adverse events (OR 2.93, 95% CI: 1.48–5.81, p = 0.002). In Cox regression, abnormal ABI predicted long-term all-cause mortality (HR 2.88, 95% CI: 1.53–5.42, p = 0.001), independent of traditional risk factors. Each 0.1 increase in AASI was linked to a 21% higher risk of the composite outcome (p = 0.001) and 25% increased risk of recurrent AMI or urgent revascularization (p = 0.001). Conclusions: In this prospective cohort of patients with AMI, ABI and AASI were associated with adverse outcomes, suggesting their potential role in risk stratification. These exploratory findings require validation in larger, multicenter cohorts to assess their incremental prognostic value and generalizability. Full article

Background: Falls are a major cause of morbidity and mortality among older adults and are influenced by comorbidities and polypharmacy. Cardiovascular diseases (CVDs) and their associated treatments are particularly prevalent in this population and may contribute to fall risk. Objectives: The objectives of this study were to examine the association between cardiovascular pharmacotherapy and fall risk in older adults and to identify potential preventive strategies. Methods: This observational case–control study was conducted between June and December 2024 and included 200 participants aged over 55 years who provided informed consent. Participants were assessed using the Downton Fall Risk Index and divided into two equal groups, with those at high risk of falling and controls. All participants underwent a comprehensive geriatric assessment, including anamnesis, clinical evaluation, and laboratory testing focused on cardiovascular risk factors. The prevalence of CVD and the use of specific cardiovascular medications were analyzed. Results: Patients at high risk of falling showed significant differences compared to the control group in several parameters, including systolic blood pressure (SBP: 140.41 mmHg vs. 151.28 mmHg, p = 0.001), ankle brachial index (left ABI: 1.09 vs. 1.15., p = 0.033), and presence of cardiovascular diseases (p = 0.001), as well as total cholesterol (p = 0.005) and triglyceride levels (p = 0.047). Certain cardiovascular medications were significantly associated with increased fall risk, including spironolactone (OR = 4.10, p = 0.001), beta-blockers (OR = 1.88, p = 0.031), and calcium channel blockers (OR = 2.05, p = 0.014), especially in combination with one another. Additional risk factors included frailty, cognitive impairment, diabetes, and neurological or osteoarticular conditions. Interventions such as medication review, deprescribing, and dosage adjustments may help reduce fall risk without compromising cardiovascular disease management. Conclusions: Cardiovascular diseases and related pharmacotherapy are significantly associated with an increased risk of falls in older adults. Regular medication reviews, deprescribing where appropriate, and individualized treatment plans may help minimize fall risk while maintaining the effective cardiovascular care of this vulnerable population. Full article

Background and Objectives: This study investigated the frequency and clinical significance of subclinical but substantial peripheral arterial disease (PAD), identified using PAD evaluation, including pulse volume recording/ankle–brachial index (PVR/ABI), transcutaneous oxygen pressure (TcpO2), and skin perfusion pressure (SPP) tests in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 54 patients with PAD evaluation results at or after AAV diagnosis. PVR/ABI and/or TcpO2 and/or SPP were performed on the same day. Abnormal PVR/ABI, TcpO2, and SPP were defined as PVR/ABI < 0.97, TcpO2 < 40 mmHg, and SPP < 50 mmHg, respectively. Poor outcomes included all-cause mortality, end-stage kidney disease (ESKD), cerebrovascular accidents, and acute coronary syndrome after PAD evaluation. Results: The median age of the 54 patients was 67 years, and 48.1% were male. In total, 3 of 54 patients (5.6%), 6 of 16 (37.5%), and 6 of 23 (26.1%) had abnormal PVR/ABI, TcpO2, and SPP, respectively. The concordance rate between abnormal PVR/ABI and abnormal TcpO2 or SPP was very low. Among the 54 patients, 5 (9.3%) died, and 2 (3.7%) progressed to ESKD. Abnormal SPP was significantly associated with cutaneous and renal manifestations at the time of PAD evaluation and had the potential to predict progression to ESKD during follow-up in patients with AAV. Conclusions: This study is the first to reveal the clinical usefulness of PAD evaluation: abnormal SPP may have the potential to identify subclinical but substantial PAD and can predict simultaneous kidney involvement as well as future progression to ESKD in patients with AAV. Full article

Introduction: Evidence for the diagnostic yield of noninvasive diagnostic assessment for the diagnosis of peripheral arterial disease (PAD) in diabetic foot syndrome (DFS) is poor. Pulse volume recordings (PVRs) at the forefoot level could be a valuable diagnostic tool in the presence of medial arterial calcification. Patients and methods: Patients with DFS who underwent invasive angiography between 01/2020 and 11/2024 and had corresponding PVRs performed within 30 days prior to the procedure were included. DFS was classified according to the Wagner–Armstrong classification. Clinical characteristics and hemodynamic parameters, including systolic ankle pressures and ankle–brachial index were recorded. PVRs were analyzed semiquantitatively by investigators blinded to the clinical information and quantitatively with determination of upstroke time (UST), upstroke ratio (USR), and maximum systolic amplitude (MSA). Angiographic PAD severity was graded according to the GLASS classification. Statistical analysis included univariate significance tests, 2 × 2 contingency tables, receiver–operator characteristic (ROC) analysis and determination of interobserver agreement. Results: In this study, 90 extremities of 70 patients were analyzed, 47 of whom had an ABI ≥ 1.3. Critical limb-threatening ischemia with non-pulsatile PVRs was evident in 6.7%. An abnormal PVR curve morphology (mildly or severely abnormal) yielded a sensitivity and specificity of 63.3% and 85.7% for detection of severe PAD (GLASS stages 2 and 3). Interobserver agreement of semiquantitative PVR rating was substantial (Cohen’s kappa 0.8) in 51 evaluated cases. For detection of any PAD (GLASS ≥ 1) or severe PAD (GLASS ≥ 2), we found the highest diagnostic accuracy for MSA (area under the curve [AUC] 0.89 and 0.82). With a cut-off value of 0.58 mmHg, MSA had a sensitivity of 91.4% and a specificity of 80.8% for detection of any PAD (GLASS ≥ 1). MSA with a cut-off of 0.27 mmHg had a sensitivity of 72.2% and a specificity of 77.1% for detection of severe PAD, whereas the sensitivity and specificity for detection of inframalleolar disease were 62.9% and 69.4%, respectively. Results were consistent in subgroup analyses. Conclusions: PVRs with extraction of quantitative features offer promising diagnostic yield for detection of PAD in the setting of DFS. MSA outperformed UST and USR but showed limited capability of detecting impaired inframalleolar outflow. Full article

This study proposes an innovative mathematical model for assessing microcirculation in patients with diabetic ulcers, using the ankle–brachial index (ABI). The methodology combines Bond Graph (BG) modeling and Particle Swarm Optimization (PSO), enabling a detailed analysis of hemodynamic patterns in a pilot sample of three patients. The results revealed a correlation between ulcer size and reduced ABI values, suggesting that deficits in microcirculation directly impact the severity of lesions. Furthermore, despite variations in ABI values and arterial pressures, all patients exhibited high capillary resistance, indicating difficulties in microcirculatory blood flow. The PSO-optimized parameters for the capillary equivalent circuit were found to be $R_1=89.784\Omega$, $R_2=426.55\Omega$, $L=27.506\mathrm{H}$, and $C=0.00040675\mathrm{F}$, which confirms the presence of high vascular resistance and reduced compliance in the microvascular system of patients with diabetic foot ulcers. This quantitative analysis, made possible through mathematical modeling, is crucial for detecting subtle changes in microcirculatory dynamics, which may not be easily identified through conventional pressure measurements alone. The increased capillary resistance observed may serve as a key indicator of vascular impairment, potentially guiding early intervention strategies and optimizing diabetic ulcer treatment. We acknowledge that the sample size of three patients represents a limitation of the study, but this number was intentionally chosen to allow for a detailed and controlled analysis of the variables involved. Although the findings are promising, additional experimental validations are necessary to confirm the clinical applicability of the model in a larger patient sample, thus solidifying its relevance in clinical practice. Full article

Background: Exercise or vitamin D intervention can reduce the risk of arterial stiffness; however, the underlying mechanisms of lipid metabolism remain unexplored. To examine the effects of a 12-week moderate and vigorous exercise program (65–80% maximal heart rate, 60 min/time, 2~3 times/week) with or without vitamin D supplementation (1000 IU/day) on the reduction in arterial stiffness and further explore whether the effects of interventions could be associated with the basal lipidome among patients with Type 2 diabetes mellitum (T2DM). Method: 61 patients with T2DM were randomly assigned to the following groups: control (CON, n = 15), exercise (EX, n = 14), vitamin D (VD, n = 16), and exercise + vitamin D (EX + VD, n = 16). Arterial stiffness risk factors (ankle–brachial index (ABI); brachial–ankle pulse wave velocity (baPWV), systolic blood pressure (SBP), and diastolic blood pressure (DBP)) were evaluated before and after the intervention. The plasma lipidome was determined using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Machine learning was applied to establish prediction models for the responsiveness to arterial stiffness. Result: Vitamin D supplementation could inhibit the decrease in the ankle–brachial index (mean ± SD: EX + VD and VD, −0.001 ± 0.058; EX + CON, −0.047 ± −0.089; p = 0.03). We observed high inter-individual variability in the arterial stiffness risk factors in response to the interventions. We also found that optimally selecting the lipid predictors at baseline, such as SM d44:6, LPE 18:2, and Hex2Cer 29:0, could enhance the predictive power by 100% for arm SBP changes in the exercise group. Basal levels of Cer (33:1) and GM3 (44:4) could enhance the predictive power by 100% for changes in baPWV in the vitamin D group. Conclusions: A 12-week vitamin D supplementation was beneficial in preventing arterial stiffness. Compared with traditional clinical risk factors, specific lipids at baseline could significantly improve the ability to predict intervention-induced changes in the reduction of arterial stiffness. Full article

Background: Transfemoral access (TFA) is a valuable alternative to upper extremity access (UEA) for branched endovascular aortic repair (bEVAR). However, TFA requires large introducer sheaths, which can reduce blood flow to lower limbs and the pelvis. This study aimed to evaluate the efficacy of sheath downsizing to maintain lower limb perfusion during TFA–bEVAR. Methods: A single-center retrospective review was conducted including patients managed with TFA-performed bEVAR between December 2020 and May 2021. Intra-operative lower limb perfusion was assessed using non-invasive ankle blood pressure measurements and great toe pulse oximetry, with measurements being taken prior to puncture (baseline), one minute after 10F-sheath insertion, three minutes after the main body delivery system insertion, and three minutes after downsizing to a 14F sheath. Outcomes included the incidence of limb perfusion reduction (LPR), defined as a drop in the ankle–brachial index (ABI) < 0.5 or peripheral oxygen saturation (SpO₂) < 90%. Results: Out of 47 patients, 24 met the inclusion criteria. LPR occurred in 4.2% of cases after 10F-sheath placement, and 87.5% after main body delivery system placement, and decreased to 12.6% after downsizing to a 14F sheath. No periprocedural major bleeding occurred. Two patients required revision for inadequate hemostasis post-operatively. SCI occurred in 16% of patients, all recovered by discharge. Pre-operative hypogastric artery occlusion was related to persistent LPR after downsizing (100% vs. 16%, p = 0.009). Conclusions: Downsizing the introducer sheath during bEVAR is feasible and safe to restore lower limb and pelvic perfusion. Further research is needed to clarify the access downsizing value during bEVAR. Full article

Background and Objectives: The interrelationship between thyroid function and the state of the cardiovascular system has been investigated both in preclinical and human studies. However, it remains unclear whether there is any association between thyroid hormones and features of subclinical cardiovascular dysfunction in euthyroid patients. Material and Methods: This study involved 45 people (females: 57.8%) with no thyroid disease who, during planned hospitalization, underwent thyroid ultrasound, determination of biochemical parameters of thyroid function, and measurement of ankle-brachial index (ABI) and toe-brachial index (TBI). People with signs of acute illness or a deterioration of their health were excluded. Results: Significant correlations were found between free triiodothyronine (FT3) and several parameters of both ABI (R = 0.347; p = 0.019 for the mean ABI taken from right side and left side values) and TBI (R = 0.396; p = 0.007 for the mean TBI taken from right side and left side values), as well as the maximal toe pressure (TP) taken from right side and left side values (R = 0.304; p = 0.045). Thyrotropin (TSH) was shown to be significantly correlated only with the maximal TBI value (taken from right side and left side values) (R = 0.318; p = 0.033), whereas free thyroxin (FT4) was shown to be significantly correlated only with the minimal TBI value (taken from right side and left side values) (R = 0.381; p = 0.01). Thyroid volume (TV) was shown to be correlated with TP (R = 0.4; p = 0.008 for the mean TP taken from right side and left side values) and some parameters of TBI value (R = 0.332; p = 0.028 for the mean TBI taken from right side and left side values), but no significant correlations were found between TVand ABI parameters. Patients with a mean ABI value ≤ 1.0 or a mean TBI value ≤ 0.75 have lower TSH, FT3, FT4, and TV than the rest of the study population, but the difference was statistically significant only for FT3. Conclusions: Even in a population of euthyroid patients with no diagnosed thyroid disease, there are some significant correlations between the volume and function of the thyroid gland and the selected features of subclinical cardiovascular dysfunction such as ABI and TBI. Full article

The results of large cardiovascular studies indicate that SGLT-2 inhibitors may increase the risk of leg amputations. This study aims to investigate whether dapagliflozin therapy affects peripheral vascular oxygenation, i.e., microcirculation in the foot, as measured by transcutaneous oxygen pressure (TcPO2) in patients with type 2 diabetes (T2DM) and peripheral arterial disease (PAD) compared to patients without PAD. The patients with PAD were randomized into two groups. In the first 35 patients with PAD, dapagliflozin was added to the therapy; in the other 26 patients with PAD, other antidiabetic drugs were added to the therapy. Dapagliflozin was added to the therapy in all patients without PAD. TcPO2 measurement, Ankle Brachial Index (ABI), anthropometric measurements, and laboratory tests were performed. After a follow-up period of 119.35 days, there was no statistically significant difference in the reduction of mean TcPO2 values between the group with T2DM with PAD treated with dapagliflozin and the group with T2DM with PAD treated with other antidiabetic drugs (3.88 mm Hg, SD = 15.13 vs. 1.48 mm Hg, SD = 11.55, p = 0.106). Patients with control TcPO2 findings suggestive of hypoxia (TcPO2 < 40 mm Hg) who were treated with dapagliflozin had a clinically significant decrease in mean TcPO2 of 10 mm Hg or more (15.8 mm Hg and 12.90 mm Hg). However, the aforementioned decrease in TcPO2 was not statistically significantly different from the decrease in TcPO2 in the group with PAD treated with other diabetic medications (p = 0.226, p = 0.094). Based on the available data, dapagliflozin appears to affect tissue oxygenation in T2DM with PAD. However, studies with a larger number of patients and a longer follow-up period are needed to determine the extent and significance of this effect. Full article

Peripheral arterial disease (PAD) prevalence and diabetes mellitus (DM) prevalence are continuously increasing worldwide. The strong relationship between DM and PAD is highlighted by recent evidence. PAD diagnosis in diabetic patients is very important, particularly in patients with diabetic foot disease (DFD); however, it is often made difficult by the characteristics of such diseases. Diagnosing PAD makes it possible to identify patients at a very high cardiovascular risk who require intensive treatment in terms of risk factor modification and medical therapy. The purpose of this review is to discuss the diagnostic methods that allow for a diagnosis of PAD in diabetic patients. Non-invasive tests that address PAD diagnosis will be discussed, such as the ankle-brachial index (ABI), toe pressure (TP), and transcutaneous oxygen pressure (TcPO2). Furthermore, imaging methods, such as duplex ultrasound (DUS), computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA), are described because they allow for diagnosing the anatomical localization and severity of artery stenosis or occlusion in PAD. Non-invasive tests will also be discussed in terms of their ability to assess foot perfusion. Foot perfusion assessment is crucial in the diagnosis of critical limb ischemia (CLI), the most advanced PAD stage, particularly in DFD patients. The impacts of PAD diagnosis and CLI identification in diabetic patients are clinically relevant to prevent amputation and mortality. Full article

Background: We performed gene therapy for critical limb ischemia in thromboangiitis obliterans (TAO) by the intramuscular administration of plasmids of the vascular endothelial growth factor gene (VEGF 165) with or without bone marrow-derived stem cells. Methods: The 21 patients were randomly assigned to three groups: A—with dual therapy, cells and plasmid; B—plasmid only; and C—control group, where patients received intramuscular injections of saline. Serum VEGF levels, the ankle–brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and the rest pain measured by the visual analog scale (VAS) were determined sequentially before treatment, and then 1 and 3 months after treatment. Results: In the treatment groups, serum VEGF levels increased by 4 weeks and returned to baseline values after 3 months. ABI after 12 weeks increased by an average of 0.18 in group A, and 0.09 in group B and group C. TcPO2 increased by an average of 17.3 mmHg in group A, 14.1 mmHg in group B, and 10.7 mmHg in group C. The largest pain decrease was observed in group A and averaged 5.43 less pain intensity. Conclusions: Gene therapy using the VEGF plasmid along with or without bone marrow-derived mononuclear cells administered intramuscularly into an ischemic limb in TAO is a safe and effective therapy. Full article