Arterial stiffness in acute COVID-19 and potential associations with clinical outcome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) interferes with the vascular endothelium. It is not known whether COVID-19 additionally affects arterial stiffness. METHODS: This case-control study compared brachial-ankle pulse wave (baPWV) and carotid-femoral pulse wave velocities (cfPWV) of acutely ill patients with and without COVID-19. RESULTS: Twenty-two COVID-19 patients (50% females, 77 [67-84] years) were compared with 22 age- and sex-matched controls. In COVID-19 patients, baPWV (19.9 [18.4-21.0] vs. 16.0 [14.2-20.4], P = 0.02) and cfPWV (14.3 [13.4-16.0] vs. 11.0 [9.5-14.6], P = 0.01) were higher than in the controls. In multiple regression analysis, COVID-19 was independently associated with higher cfPWV (ß = 3.164, P = 0.004) and baPWV (ß = 3.532, P = 0.003). PWV values were higher in nonsurvivors. In survivors, PWV correlated with length of hospital stay. CONCLUSION: COVID-19 appears to be related to an enhanced PWV reflecting an increase in arterial stiffness. Higher PWV might be related to an increased length of hospital stay and mortality.

Micro- and macrovascular function in patients suffering from primary adrenal insufficiency: a cross-sectional case-control study.

BACKGROUND: Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, patients suffering from primary adrenal insufficiency (AI) have an increased mortality, mainly due to cardiovascular diseases. Only little knowledge exists on the contribution of MC substitution to the cardiovascular risk. Therefore, this study investigates the impact of plasma renin concentration on parameters of micro- and macrovascular function. METHODS: 26 patients with primary AI [female = 18, age: 51 (28; 78) years; BMI: 24 (18; 40) kg/m2; disease duration: 18 (5; 36) years] were included in this cross-sectional analysis. Intima media thickness (IMT) and pulse wave velocity (PWV) were investigated to assess macrovascular remodeling and arterial stiffness. Microvascular function was estimated by post-occlusive reactive hyperemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded. Patients were grouped according to their median plasma renin concentration of previous visits (Reninhigh vs Reninlow) and were compared to a group of healthy women [age: 44 (43; 46) years; BMI: 24.2 (21.8; 27.5)]. RESULTS: PWV was significantly higher in AI patients compared to controls [9.9 (5; 18.5) vs 7.3 (6.8; 7.7) m/s; p < .01], whereas no differences in microvascular function could be found. In Reninlow time to peak perfusion was significantly longer [6.0 (3; 15) vs 3.5 (1.5; 11) s; p < .05], whereas no differences in IMT and PWV were observed between Reninhigh and Reninlow. No impact of GC dose was observed. CONCLUSIONS: Microvascular function is not impaired in patients with primary AI under adequate replacement therapy, although higher renin concentrations are associated with subclinical improvements. No relation between RAAS activity and macrovascular function is observed, while arterial stiffness might be increased in primary AI.

Chronic inflammation predicts long-term mortality in patients with Raynaud's phenomenon.

BACKGROUND: Subclinical chronic inflammation could be the driving force behind the recently revealed association between abnormal nailfold capillaries as well as autoantibodies and long-term mortality in patients with incipient Raynaud's phenomenon. Whether laboratory markers that reflect a chronic inflammatory process are directly related to mortality in Raynaud's phenomenon is not known. METHODS: In total, 2958 patients with incipient Raynaud's phenomenon without previously known connective tissue disease (CTD) were enrolled. At their initial presentation, laboratory tests for C-reactive protein (CRP), leucocytes, fibrinogen and the haemoglobin concentration were obtained. In addition, nailfold capillaries and antinuclear antibodies (ANA) were assessed. Patients' mortality was recorded through a median follow-up period of 9.3 years. RESULTS: Baseline CRP, fibrinogen and haemoglobin concentration were associated with long-term mortality in an individual analysis of patients with incipient Raynaud's phenomenon. In a multivariable model including patients' age, nailfold capillaries and ANA, a low haemoglobin concentration remained independently related to future mortality. Amongst potential predictors for mortality in patients with Raynaud's phenomenon, a low haemoglobin concentration was most strongly related to patients' mortality risk. CONCLUSION: In Raynaud's phenomenon, laboratory markers that can be attributed to a chronic inflammatory state independently yield prognostic information in addition to the presence of abnormal nailfold capillaries and ANA. Amongst all prognostic markers, the haemoglobin concentration is most strongly related to patients' mortality in Raynaud's phenomenon.

Speckle-Tracking-Based Evaluation of Vascular Strain at Different Sites of the Arterial Tree in Healthy Adults.

Purpose: Vascular ultrasound (US) allows the analysis of vascular strain by speckle-tracking. This study sought to assess the extent to which vas cular strain varies between different segments of the arterial tree. Furthermore, this study aimed to investigate the reproducibility of vascular strain determination as well as of the components that contribute to the variance of vascular strain measurements in different vascular beds. Materials and Methods: Speckle-tracking was used to determine the vascular strain of the abdominal aorta (AA), the common carotid artery (CCA), the common femoral (CFA) and the popliteal artery (PA) of healthy adults. Intra- and interday reproducibility and the components of variance of vascular strain of the respective arteries were determined. Results: A total of 589 US clips obtained in 10 healthy adults (7 males, 28.3 ±â€Š3.2 years) were analyzable. Vascular strain was 7.2 ±â€Š3.0 % in the AA, 5.7 ±â€Š2.1 % in the CCA, 2.1 ±â€Š1.1 % in the CFA and 1.9 ±â€Š1.1 % in the PA. The intraday coefficients of variation of vascular strain were 6.2 % (AA), 3.9 % (CCA), 3.3 % (CFA) and 6.1 % (PA), and the interday coefficients of variation were 5.9 % (AA), 8.4 % (CCA), 10 % (CFA) and 4.6 % (PA). The variance of vascular strain mainly depended on the investigated vessel and subject. Individual DUS clips, the day of examination and the (right/left) body side (in paired arteries) had no impact on the variance of vascular strain. Conclusion: Vascular strain substantially varies between different sites of the arterial tree. Speckle-tracking by DUS allows the reliable determination of vascular strain at different arterial sites.

Associations of nailfold capillary abnormalities and immunological markers in early Raynaud's phenomenon.

OBJECTIVES: Nailfold capillaroscopy (NC) and laboratory tests for antinuclear antibodies (ANA) are routinely used in parallel for detection of emerging connective tissue disease (CTD) in patients with Raynaud's phenomenon (RP). The aim of this study was to assess the associations between distinct nailfold capillary abnormalities and concomitant autoantibodies in patients with incipient RP without previously known CTD. METHOD: Patients with incipient RP without previously known CTD were included in this retrospective analysis. We analysed the association of particular capillary abnormalities (reduced density, avascular fields, dilations, giant capillaries, haemorrhages, tortuosity, ramifications, oedema) with ANA and ANA subsets (anti-Scl-70, anti-CENP-B, anti-U1-RNP, anti-dsDNA, anti-SSA(Ro), anti-SSB(La), anti-Sm, and anti-Jo-1 antibodies). We also developed a score that allows the estimation of each patient's individual probability for the presence of an ANA titre ≥ 1:160. RESULTS: The final analysis comprised 2971 patients. Avascular fields, giant capillaries, reduced capillary density, and capillary oedema were closely related to an ANA titre ≥ 1:160. Both giant capillaries and avascular fields were associated with anti-Scl-70 and anti-CENP-B antibodies. Only a weak association was found between giant capillaries and anti-U1-RNP antibodies. Each patient's individual probability for the presence of an ANA titre ≥ 1:160 can be represented by a sum score comprising giant capillaries, reduced density, avascular fields, ramifications, and oedema as well as patients' sex and age. CONCLUSION: In patients with incipient RP, anti-Scl-70 and anti-CENP-B antibodies are related most specifically to distinct capillary alterations. Although a sum score can represent the patient's probability for elevated ANA titres, NC cannot substitute for immunological tests in patients with incipient RP.

Microvascular autoregulation in children and adolescents with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Deterioration of microvascular function may have an early onset in individuals with type 1 diabetes mellitus. We hypothesised that microvascular autoregulation is impaired in children with type 1 diabetes and can be detected non-invasively by postocclusive reactive hyperaemia (PORH). METHODS: Microvascular autoregulation was assessed in 58 children with type 1 diabetes and 58 age- and sex-matched healthy controls by PORH using laser Doppler fluxmetry. Baseline perfusion, biological zero (defined as a 'no flow' laser Doppler signal during suprasystolic occlusion), peak perfusion following occlusion, time to peak and recovery time (time until baseline perfusion is resumed) were recorded and compared between the groups. RESULTS: Peak perfusion was higher in children with type 1 diabetes than in healthy controls (1.7 ± 0.93 AU [arbitrary units] vs 1.29 ± 0.46 AU; p = 0.004), and biological zero was lower in children with type 1 diabetes vs controls (0.14 ± 0.04 AU vs 0.19 ± 0.04 AU; p < 0.0001). No differences were seen between the groups in baseline perfusion, time to peak during PORH and recovery time following PORH. CONCLUSIONS/INTERPRETATION: PORH reveals impaired microvascular autoregulation in children with type 1 diabetes. The higher peak perfusion might reflect a decline in the vasoconstrictive ability of arteriolar smooth muscle cells upstream of capillary beds in children with type 1 diabetes.

Wall shear stress in the superficial femoral artery of healthy adults and its response to postural changes and exercise.

OBJECTIVES: Alterations of wall shear stress (WSS) are considered to precede atherosclerosis. Local variations of WSS might contribute to the typical distribution of atherosclerotic lesions along the superficial femoral artery (SFA). We investigated the course of WSS and its response to postural changes and exercise along the SFA of healthy adults. METHODS: In forty-six healthy subjects, we determined flow velocities and internal vessel diameters in five predefined segments of the SFA using duplex ultrasound; measurements were done at rest, following exercise (30 toe raises) and after postural changes (supine and sitting). Peak and mean WSS were calculated from peak systolic and mean velocities, vessel diameter and whole blood viscosity. RESULTS: At rest, peak and mean WSS did not vary along the femoro-popliteal axis (p > 0.05); peak and mean WSS were lower in the sitting than in the supine position (p < 0.0001). After exercise, peak and mean WSS increased in all segments (p < 0.0001), showing the lowest increase in the distal Hunter's canal. CONCLUSION: Healthy adults do not exhibit local variations of WSS in the SFA at rest, but segmental differences in WSS occur after exercise. Whether these findings are related to the typical distribution of atherosclerotic lesions later in life requires further investigation.

Renal artery stenosis predicts adverse cardiovascular and renal outcome in patients with peripheral artery disease.

BACKGROUND: Patients with symptomatic peripheral artery disease (PAD) are considered cardiovascular high-risk patients. Our aim was to investigate whether incidental renal artery stenosis (RAS) increases the risk for adverse cardiovascular and renal outcomes in these patients. MATERIALS AND METHODS: We prospectively enrolled 487 consecutive patients admitted for revascularization of symptomatic PAD and performed a renal overview angiogram categorizing RAS as absent (0-29%), moderate (30-59%) and severe (>or= 60%) respectively. Clinical follow-up was for median 15 months (IQR 12-22) for the occurrence of major adverse events [MAE: composite of death, myocardial infarction (MI), stroke, percutaneous coronary intervention, coronary bypass surgery, amputation and kidney failure]. Glomerular filtration rates (GFR) were obtained at 12 months to quantify the course of renal function. RESULTS: A severe RAS was found in 76 patients (15.6%). Overall MAE occurred in 121 patients (24.8%), the composite endpoint of MI, stroke, amputation and death occurred in 101 patients (20.7%). Patients with a severe RAS had a 1.87-fold increased adjusted risk for MAE (95% CI 1.12-3.12, P = 0.017), a 2.51-fold increased adjusted risk for occurrence of the composite endpoint of MI, stroke, amputation and death (95% CI 1.45-4.34, P = 0.001) and a 2.93-fold increased risk for death (95% CI 1.41-6.08, P = 0.004), compared to those of patients without RAS respectively. We observed a significant association between the decrease of GFR over the 12-month follow-up period and the severity of RAS by multivariable analysis (P = 0.044). CONCLUSION: Severe RAS in patients with symptomatic PAD is an independent predictor of major adverse cardiovascular events, adverse renal outcome and mortality.

Impact of international guidelines on the management of cardiovascular risk factors in diabetic patients with peripheral arterial disease.

AIM: Recent data on the management of cardiovascular risk factors in high risk patients showed that dyslipidemia is still treated in an inadequate way, especially in diabetic patients. We wanted to analyze the impact of the recommendation of the Inter-Society Consensus for the management of PAD (TASC-II) on the actual situation. METHODS: In this retrospective cohort study we analyzed total-, HDL-, LDL-cholesterol, triglycerides and blood glucose using capillary blood in diabetic patients, admitted to our outpatient department. Besides the recording of a complete medical history and vascular risk factors, an ABI-measurement and a carotid Duplex ultrasonography were performed at presentation. RESULTS: We studied 111 diabetic patients (44 female and 67 male) with a mean age (+/-SD) of 70, 3 (+/-9, 9) years; a BMI of 28, 2 (+/-4, 2) and a mean waist circumference of 103 (+/-12, 2) cm. Metabolic syndrome according to the NCEP-ATP-III criteria (2001) was shown in 86% (N.=95). 41% (N.=45) had clinically manifest vascular disease in a second and 23% (N.=26) even in a third vascular territory. Total-cholesterol was 183+/-43 mg/dL; LDL-C 94 +/-30 mg/dL; HDL-cholesterol 44 +/-12 mg/dl and triglycerides 219+/-103 mg/dL. A total of 33% (N.=37) in this high risk cohort attained the LDL-C target levels according to the TASC-II guidelines. A total of 68% (N.=76) was on a HMG-CoA-reductase-inhibitor, 61% (N.=68) had platelet aggregation inhibitors. CONCLUSIONS: We found poor adherence to international guidelines for secondary prevention in diabetic patients with PAD in this outpatient setting.

Haem oxygenase-1 genotype and cardiovascular adverse events in patients with peripheral artery disease.

BACKGROUND: A functional GT dinucleotide length polymorphism in the haem oxygenase-1 (HO-1) gene promoter is thought to be involved in the pathogenesis of cardiovascular disease. Short (< 25) (GT)n repeats are suggested to facilitate enhanced HO-1 up-regulation in response to injury and confer potent anti-inflammatory and antioxidative effects. MATERIALS AND METHODS: We investigated the association between the HO-1 GT-polymorphism and cardiovascular outcome in 472 patients with advanced peripheral artery disease. Cardiovascular risk profile and DNA samples for determination of the HO-1 genotype (carrier vs. noncarrier of a short (GT)n repeat allele) were obtained at baseline, and patients were followed for median 21 months for the occurrence of coronary events (myocardial infarction, percutaneous coronary interventions and coronary artery bypass graft), cerebrovascular events (stroke or carotid revascularization) and all-cause mortality. RESULTS: Coronary events occurred in 48 patients (9%), cerebrovascular events in 40 patients (9%) and 59 patients (13%) died. In total, 173 major adverse cardiovascular events (MACE) occurred in 133 patients (28%). Carriers of the short (GT)n repeat allele had a 0.46-fold reduced adjusted hazard ratio for coronary events (P = 0.016) as compared to noncarriers. No significant difference was found for cerebrovascular events, mortality and overall MACE. CONCLUSION: Apparently, the HO-1 genotype exerts potentially protective effects against coronary adverse events in patients with peripheral artery disease. Homozygous and heterozygous carriers of < 25 (GT)n repeats had lower rates of myocardial infarction, percutaneous coronary interventions and coronary bypass operations compared to patients with longer (GT)n repeats.

Outcome of conservative therapy of patients with severe intermittent claudication.

BACKGROUND: Intermittent claudication due to peripheral artery disease (PAD) can be treated conservatively, or by revascularization. OBJECTIVES: To assess the short-term outcome of conservatively-treated claudicants, and determine predictors for clinical improvement. Design. A retrospective cohort study. METHODS: We evaluated Fontaine stage, walking distance and ankle brachial index (ABI) at baseline and after median 9 months (interquartile range (IQR) 6-24) in 181 patients with severe claudication. RESULTS: We found clinical improvement by at least one Fontaine stage in 38 patients (21%) with an increased walking distance from baseline median 100 m (IQR 50-150) to follow-up median 650 m (IQR 300 to unlimited; p<0.001), but without changes in ABI (median 0.57, IQR 0.48-0.73 vs. median 0.54, IQR 0.45-0.81; p=0.10). One hundred and thirty-eight patients (76%) remained clinically and hemodynamically stable. A worsening of the clinical stage but without amputation was recorded in five patients (3%). Female gender (hazard ratio (HR) 0.51, p=0.052), diabetes (HR 0.35, p=0.020), and baseline ABI below 0.44 (HR 0.31, p=0.019) were associated with a reduced probability of clinical improvement. CONCLUSION: Certain patients with intermittent claudication show substantial clinical improvement with conservative medical therapy, despite any lack of hemodynamic improvement. Given the low number of patients with clinical deterioration in the short term, primarily conservative therapy should be the preferred initial option for most claudicants.