Association of plasma soluble α-klotho with pro-endothelin-1 in patients with type 2 diabetes

Objectives

To study the relationship between plasma soluble klotho (sKlotho) and pro-endothelin-1 (proET-1) in patients with type 2 diabetes (T2DM).

Subjects and methods

In this cross-sectional study, we recruited 175 T2DM subjects and 56 non-diabetic controls. Plasma sKlotho, proET-1 and extracellular superoxide dismutase (SOD) were measured by ELISA and ILMA, respectively.

Results

Plasma sKlotho level in patients with T2DM was lower compared to that in non-diabetic controls (416.8 ± 148.1 vs. 494.6 ± 134.3 pg/ml, p = 0.001) and showed significant interaction with diabetes status in its association with proET-1. Plasma sKlotho was inversely correlated with proET-1 in T2DM (Rho = −0.410, p < 0.0001) but not in non-diabetic controls (Rho = 0.091, p = 0.505). Multivariable linear regression models revealed that sKlotho was independently associated with proET-1 after adjustment for renal filtration function, albuminuria, diabetes duration, HbA1c, systolic and diastolic blood pressure.

Conclusions

Plasma sKlotho was associated with proET-1 independent of renal function in patients with T2DM.     

High-risk plaque in the superficial femoral artery of people with peripheral artery disease: Prevalence and associated clinical characteristics

Objective

We used magnetic resonance imaging (MRI) to study the prevalence and associated clinical characteristics of high-risk plaque (defined as presence of lipid-rich necrotic core [LRNC] and intraplaque hemorrhage) in the superficial femoral arteries (SFA) among people with peripheral artery disease (PAD).

Background

The prevalence and clinical characteristics associated with high-risk plaque in the SFA are unknown.

Methods

Three-hundred-three participants with PAD underwent MRI of the proximal SFA using a 1.5 T S platform. Twelve contiguous 2.5 mm cross-sectional images were obtained.

Results

LRNC was present in 68 (22.4%) participants. Only one had intra-plaque hemorrhage. After adjusting for age and sex, smoking prevalence was higher among adults with LRNC than among those without LRNC (35.9% vs. 21.4%, p = 0.02). Among participants with vs. without LRNC there were no differences in mean percent lumen area (31% vs. 33%, p = 0.42), normalized mean wall area (0.71 vs. 0.70, p = 0.67) or maximum wall area (0.96 vs. 0.92, p = 0.54) in the SFA. Among participants with LRNC, cross-sectional images containing LRNC had a smaller percent lumen area (33% ± 1% vs. 39% ± 1%, p < 0.001), greater normalized mean wall thickness (0.25 ± 0.01 vs. 0.22 ± 0.01, p < 0.001), and greater normalized maximum wall thickness (0.41 ± 0.01 vs. 0.31 ± 0.01, p < 0.001), compared to cross-sectional images without LRNC.

Conclusions

Fewer than 25% of adults with PAD had high-risk plaque in the proximal SFA using MRI. Smoking was the only clinical characteristic associated with presence of LRNC. Further study is needed to determine the prognostic significance of LRNC in the SFA.

Clinical trial registration—URL

http://www.clinicaltrials.gov. Unique identifier: NCT00520312.     

Protective Effects of Tight Glucose Control During Cardiopulmonary Bypass on Myocardium in Adult Nondiabetic Patients Undergoing Valve Replacement

Background

In this study, we aimed to evaluate the protective effect of tight glucose control during cardiopulmonary bypass on myocardium in adult nondiabetic patients undergoing isolated aortic valve replacement in a prospective and randomized trial.

Methods

Sixty-five adult nondiabetic patients undergoing selective isolated aortic valve replacement were enrolled and randomly assigned to an insulin group (patients received a continuous insulin infusion during surgery; n = 33) or a control group (patients were not administered insulin unless their blood glucose level exceeded 200 mg/dL; n = 32). Cardiac troponin I was assayed preoperatively, and then at 2, 6, 12, 24, and 48 hours after aortic cross-declamping. The pre-, intra-, and postoperative relevant data of all selected patients were analyzed.

Results

Tight glucose control reduced postoperative peak release by 48% for cardiac troponin I compared with the control group (0.48 ± 0.12 vs 0.71 ± 0.17 ng/mL; P < 0.0001). Patients with continuous insulin infusion had lower peak inotropic score during the first postoperative 24 hours and peak level of blood glucose (5.8 ± 2.2 vs 8.2 ± 3.1 μg/kg/min; P < 0.0001; 131.9 ± 23.8 vs 191.1 ± 38.5 mg/dL; P < 0.001, respectively), shorter duration of mechanical ventilation and intensive care unit stay and hospital stay compared with the control group (11.6 ± 2.9 hours vs 14.8 ± 3.5 hours; P = 0.0002; 28.4 ± 7.2 hours vs 36.5 ± 7.8 hours; P < 0.0001; 9.4 ± 3.3 days vs 11.5 ± 4.2 days; P = 0.0283, respectively).

Conclusions

Tight glucose control during cardiopulmonary bypass might provide myocardial protection in adult nondiabetic patients undergoing isolated aortic valve replacement.     

Validation of a Portuguese version of the Information Needs in Cardiac Rehabilitation (INCR) scale in Brazil

Objectives

To translate, culturally adapt and psychometrically validate the Information Needs in Cardiac Rehabilitation (INCR) tool to Portuguese.

Background

The identification of information needs is considered the first step to improve knowledge that ultimately could improve health outcomes.

Methods

The Portuguese version generated was tested in 300 cardiac rehabilitation patients (CR) (34% women; mean age = 61.3 ± 2.1 years old). Test-retest reliability was assessed using intraclass correlation coefficient (ICC), the internal consistency using Cronbach's alpha, and the criterion validity was assessed with regard to patients' education and duration in CR.

Results

All 9 subscales were considered internally consistent (á > 0.7). Significant differences between mean total needs and educational level (p < 0.05) and duration in CR (p = 0.03) supported criterion validity. The overall mean (4.6 ± 0.4), as well as the means of the 9 subscales were high (emergency/safety was the greatest need).

Conclusion

The Portuguese INCR was demonstrated to have sufficient reliability, consistency and validity.     

Prognostic significance of six-minute walk test in non-group 1 pulmonary hypertension

Objective

To assess the value of the six-minute walk test (6MWT) to predict outcome in non-group 1 pulmonary hypertension (PH).

Background

Distance walked during 6MWT has been widely used as a prognostic test in pulmonary arterial hypertension (group 1 pulmonary hypertension); however, little is known regarding its prognostic value in other groups of PH.

Methods

This was a retrospective study of 60 patients diagnosed of PH, Dana Point classification groups 2–5. 6MWT and echocardiography were performed in all cases.

Results

Forty patients (66.6%) were females. Mean age was 70.8 ± 10.7 years (range: 32–85). Seven patients died after a mean follow-up of 23.2 ± 16.7 months. Distance <400 m during 6MWT was associated with a higher risk for death (RR: 4.39; 95% CI: 1.13-17.05; p = 0.03) and for clinical deterioration (death or need for hospitalization) (RR: 2.76; 95% CI: 1.18–6.42; p = 0.02).

Conclusions

6MWT is useful to predict outcome in non-group 1 PH.     

The MoCA and MMSE as screeners for cognitive impairment in a heart failure population: A study with comprehensive neuropsychological testing

Objective

To examine the ability of the Mini Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to detect cognitive impairment in persons with heart failure (HF).

Background

Although the MMSE and MoCA are commonly used screeners in HF, no research team has validated their performance against neuropsychological testing.

Methods

Participants were 106 patients with HF (49.1% male, 68.13 ± 9.82 years) who completed the MoCA, MMSE, and a full neuropsychological battery. Sensitivity and specificity were examined. Discriminant function analyses tested whether the screeners correctly detected cognitive impairment.

Results

A MoCA score <25 and MMSE score of <28 yielded optimal sensitivity/specificity (.64/.66 and .70/.66, respectively). The MoCA correctly classified 65% of patients, Wilk's lambda = .91, χ²(1) = 9.89, p < .01, and the MMSE correctly classified 68%, Wilk's lambda = .87, χ²(1) = 14.26, p < .001.

Conclusions

In HF, both the MoCA and MMSE are useful in identifying the majority of patients with and without cognitive impairment. Both tests misclassified approximately one-third of patients, so continued monitoring and evaluation of patients is needed in conjunction with screening.     

The effect of cardiac genetic testing on psychological well-being and illness perceptions

Objective

To assess the effects of positive cardiac genetic diagnoses, ICD discharges, and arrhythmias on measures of psychological well-being.

Methods

Fifty-eight adults with prior cardiac genetic testing were enrolled. Patient well-being was determined using the SF-36 (QoL), HADS-A and HADS-D (anxiety/depression), and IPQ-R (patients' perceptions of illness). Patients with positive and negative cardiac genetic test results were compared using non-parametric statistics.

Results

Genetic testing yielded 76% with a positive diagnosis and 29% reported an ICD shock. QoL assessments (n = 33) were within normal ranges (mean of 50) with the exceptions of general health (44.1 ± 12.2, p < 0.01) and bodily pain (55.1 ± 9.1, p < 0.01) domains, but only the bodily pain domain showed differences between those with positive and negative cardiac genetic test results. Subjects with ICD discharges had higher scores than those without shocks in consequential and emotional IPQR subscales as well as greater perceived risks of experiencing a serious cardiac event, developing additional symptoms, or limitations in daily activities.

Conclusion

Positive genetic results did not negatively impact patient well-being with the exception of the bodily pain domain of the SF-36.     

Orosomucoid secretion levels by epicardial adipose tissue as possible indicator of endothelial dysfunction in diabetes mellitus or inflammation in coronary artery disease

Objective

Type 2 diabetes mellitus (T2DM) is associated with fat and autonomic system dysfunction. Epicardial adipose tissue (EAT) plays an endocrine role over the heart. Since orosomucoid (ORM) has local actions around the coronaries, our aim was to assess the relationship between its secretion profile by EAT and its catecholaminergic regulation in patients with T2DM and coronary artery disease (CAD).

Methods

We obtained EAT, subcutaneous adipose tissue (SAT) and plasma from 55 patients undergoing cardiac surgery. Fat explants were stimulated with isoproterenol (ISO) 1 μM for 6 h. After, the fat explants released-ORM and plasma levels were analyzed by ELISA. mRNA or protein expression was analyzed by real time PCR or western blot, respectively. The effects of ORM on endothelial cells were analyzed by impedance and wound healing assays.

Results

We observed that EAT-released ORM levels were higher than SAT (328 ± 185 vs 58 ± 45 ng/mL; p < 0.001). Interestingly, EAT secretion was lower in patients with than those without T2DM (260 ± 141 vs 370 ± 194 ng/mL; p < 0.05) and this difference was enhanced after ISO stimulation (p < 0.01). However, plasma levels (412 ± 119 vs 594 ± 207 μg/mL) and EAT-released ORM levels were higher in patients with than those without CAD (384 ± 195 vs 279 ± 159 ng/mL; p < 0.05). ISO stimulation, also reduced the EAT released-ORM levels in patients with CAD. On human endothelial cells, ORM induced an increase of healing and proliferation in a dose-dependent manner.

Conclusion

EAT-released ORM levels in patients with T2DM or CAD and its regulation by catecholamines might be the mirror of local endothelium dysfunction or inflammatory process in different cardiovascular disorders.     

Association of Lp-PLA2 with digital reactive hyperemia,coronary flow reserve,carotid atherosclerosis and arterial stiffness in coronary artery disease

Background

Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has a powerful inflammatory and atherogenic action in the vascular wall and is an independent marker of poor prognosis in coronary artery disease (CAD). We investigate the association of Lp-PLA2 with markers of vascular dysfunction and atherosclerosis with proven prognostic value in CAD.

Methods

In 111 patients with angiographically documented chronic CAD, we measured 1) carotid intima-media thickness (CIMT), 2) reactive hyperemia using fingertip peripheral arterial tonometry (RH-PAT), 3) coronary flow reserve (CFR), by Doppler echocardiography 4) pulse wave velocity (PWV) and 5) blood levels of Lp-PLA2.

Results

Patients with Lp-PLA2 concentration >234.5 ng/ml (50th percentile) had higher CIMT (1.44 ± 0.07 vs. 1.06 ± 0.06 mm), PWV (11.0 ± 2.36 vs. 9.7 ± 2.38 m/s) and lower RH-PAT(1.24 ± 0.25 vs. 1.51 ± 0.53) and CFR (2.39 ± 0.75 vs. 2.9 ± 0.86) compared to those with lower Lp-PLA (p < 0.05 for all comparisons). Lp-PLA2 was positively associated with CIMT (regression coefficient b: 0.30 per unit of Lp-PLA2, p = 0.02), PWV (b:0.201, p = 0.04) and inversely with RHI-PAT (b: −0.371, p < 0.001) and CFR (b:−0.32, p = 0.002). In multivariate analysis, Lp-PLA2 was an independent determinant of RHI-PAT, CFR, CIMT and PWV in a model including age, sex, smoking, diabetes, dyslipidemia and hypertension (p < 0.05 for all vascular markers). Lp-PLA2, RHI-PAT and CFR were independent predictors of cardiac events during a 3-year follow-up.

Conclusions

Elevated Lp-PLA2 concentration is related with endothelial dysfunction, carotid atherosclerosis, impaired coronary flow reserve and increased arterial stiffness and adverse outcome in CAD patients. These findings suggest that the prognostic role of Lp-PLA2 in chronic CAD may be explained by a generalized detrimental effect of this lipase on endothelial function and arterial wall properties.     

Laparoscopic gastric banding resolves the metabolic syndrome and improves lipid profile over five years in obese patients with body mass index 30–40 kg/m

Background

Obesity, metabolic syndrome (MS) and dyslipidemia are independent risk factors for cardiovascular disease. Bariatric surgery is increasingly recognized as an effective intervention for improving each of these risk factors. There are sparse data on the long-term durability of metabolic changes associated with bariatric surgery, in particular with laparoscopic gastric banding (LGB). Our objective was to evaluate the durability of metabolic changes associated with LGB in nonmorbid obesity.

Methods

Fifty obese patients (BMI 30–40) with ≥1 obesity-related comorbidity were prospectively followed for five years. At follow-up, subjects underwent fasting blood measures, including lipid NMR spectroscopy and standard lipid profile.

Results

Forty-seven patients (45 female, mean age 43.8 years) completed four years follow-up (46 completed five years). Baseline BMI was 35.1 ± 2.6. Subjects exhibited mean weight loss of 22.3 ± 7.9 kg (22.9 ± 7.4%) at year one and maintained this (19.8 ± 10.2%) over five years. At baseline, 43% (20/47) of subjects met criteria for MS. This was reduced to 15% (7/47) at year one and remained reduced over five years (13%, 6/46) (p < 0.001). There were reductions in triglycerides (p < 0.001) and increases in HDL cholesterol (HDL-C, p < 0.001) and HDL particle concentration (p = 0.02), with a trend toward increased HDL particle size (p = 0.06) at year five. Changes in triglycerides and HDL-C were more prominent in patients with MS at baseline, but unassociated with weight loss or waist circumference. Changes in HDL particle size and concentration were not associated with MS status, weight loss, waist circumference, or statin use.

Conclusions

LGB produces significant weight loss, resolution of MS and changes in lipid profile suggestive of beneficial HDL remodeling. These changes persist five years following LGB.     

Comparison of cardiopulmonary exercise testing variables in COPD patients with and without coronary artery disease

Background

Coronary artery disease (CAD) is a common concomitant condition and an important cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Since COPD and CAD can both independently cause reduced exercise capacity, it is reasonable to hypothesize that the combination of these diseases may compound the abnormalities observed during cardiopulmonary exercise testing (CPET). However, little is known about the impact of CAD on the CPET response in COPD patients. The aim of this study is to compare exercise capacity and gas exchange variables in COPD patients with and without CAD.

Methods

Fifty-four COPD subjects without CAD (COPDnoCAD) were matched to 54 COPD subjects diagnosed with CAD (COPD/CAD) according to age, gender, body mass index and severity of COPD. All subjects underwent resting pulmonary function and symptom-limited CPET.

Results

Comparing COPDnoCAD patients with COPD/CAD patients revealed that exercise capacity, as measured by % peak oxygen consumption (42 ± 16% vs 53 ± 19%, p = 0.002) and % peak wattage (23 ± 13% vs 32 ± 16%, p = 0.001), was significantly lower in COPD/CAD. Ventilatory response, as measured by VE/VCO₂ nadir (36 ± 9 vs 32 ± 5, p = 0.001), was significantly higher in COPD/CAD, with % peak VO₂ and VE/VCO₂ nadir correlating to % FEV₁ and inversely correlating with %DLCO.

Conclusion

COPD patients with CAD have significantly impaired CPET responses with lower exercise capacity and impaired gas exchange compared to COPD patients without CAD. These findings may affect the clinical interpretation of CPET data in COPD patients who have concomitant CAD.     

Cardiocerebral resuscitation improves survival of patients with out-of-hospital cardiac arrest

Purpose

The guidelines for cardiopulmonary resuscitation (CPR) have been in place for decades; but despite their international scope and periodic updates, there has been little improvement in survival rates in out-of-hospital cardiac arrest for patients who did not receive early defibrillation. The Emergency Medical Service directors in 2 rural Wisconsin counties initiated a new protocol for the pre-hospital management of adult cardiac arrest victims in an attempt to improve survival rates. The results observed after implementation of this protocol are presented and compared with those observed during a three-year period that preceded initiation of the project.

Methods

The protocol, based upon the principles of cardiocerebral resuscitation, was significantly different from the standard CPR protocol. A major objective was to minimize interruptions of chest compressions. Each defibrillation, including the first, was preceded by 200 uninterrupted chest compressions. Single shocks, rather than stacked shocks, were utilized. Post shock rhythm and pulse checks were eliminated, and chest compressions were resumed immediately after a shock was delivered. Initial airway management was limited to an oral pharyngeal device and supplemental oxygen. If the arrest was witnessed, assisted ventilations and intubation were delayed until either a return of spontaneous circulation or until three series of “compressions + analysis ± shock” were completed.

Results

In the 3 years preceding the change in protocol, where standard CPR was utilized, there were 92 witnessed out-of-hospital adult cardiac arrests with an initially shockable rhythm. Eighteen patients survived, and 14 of 92 (15%) were neurologically intact. After implementing the new protocol in early 2004, there were 33 witnessed out-of-hospital adult cardiac arrests with an initially shockable rhythm. Nineteen survived, and 16 of 33 (48%) were neurologically normal. Differences in both total and neurologically normal survival are significant (chi-squared = 0.001).

Conclusion

Instituting the new cardiocerebral resuscitation protocol for managing prehospital cardiac arrest improved survival of adult patients with witnessed cardiac arrest and an initially shockable rhythm.     

Undercarboxylated osteocalcin relates to cardiovascular risk markers in offspring of families with metabolic syndrome

Background

The undercarboxylated form of osteocalcin (ucOC) is an emerging marker of cardiovascular disease. It is unknown if ucOC in related to common cardiovascular risk markers in children. In offspring of families with and without metabolic syndrome (MetS+ and MetS− families), we assessed whether ucOC was related to a continuous metabolic syndrome score (MetS score) and to carotid intima–media thickness (cIMT).

Methods

ucOC and total OC, MetS score and cIMT were assessed in 203 asymptomatic prepubertal children (age 7.6 ± 0.1 yr; 49% girls), of whom 99 were from MetS+ families.

Results

In children from MetS+ families, percent ucOC was higher than in children from MetS− families (p < 0.01). In offpring from MetS+ families, higher ucOC and especially higher percent ucOC was independently associated with both the MetS score and cIMT (both p ≤ 0.01).

Conclusions

The undercarboxylated form of OC is related to common cardiovascular risk markers in children at risk for cardiovascular disease.     

Alterations in plasma lecithin:cholesterol acyltransferase and myeloperoxidase in acute myocardial infarction: Implications for cardiac outcome

Background

The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), plays a key role in HDL maturation and remodeling. Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the extent to which plasma LCAT activity is altered in acute myocardial infarction (MI) in conjunction with abnormal MPO levels. We also assessed the impact of LCAT and MPO on newly developed major adverse cardiovascular events (MACE).

Methods

Two-hundred one consecutive patients referred for acute chest pain of whom 134 had MI (95 with ST-elevation) participated. Forty-five new MACE were ascertained during 1203 (range 13–1745) days of follow-up among 185 patients. Plasma LCAT activity was measured using an exogenous substrate assay. MPO mass was assayed by chemiluminescent microparticle immunoassay.

Results

Plasma LCAT activity was decreased by 15%, coinciding with 7-fold increased MPO levels in acute MI patients vs. patients with non-cardiac chest pain (p < 0.001 for both; correlation: r = −0.343, p < 0.001). MI at admission was associated independently with both lower plasma LCAT activity and higher MPO (age- and sex-adjusted odds ratio per 1 SD increment: 0.46 (95% CI, 0.31–0.68), p < 0.001 and 7.58 (95% CI, 3.34–17.11), p < 0.001, respectively). In an analysis with LCAT and MPO together these associations were modestly attenuated. MPO mass (hazard ratio: 1.59 (95% CI, 1.15–2.19), p = 0.004), but not LCAT activity (hazard ratio: 0.87 (95% CI, 0.65–1.19), p = 0.39), predicted newly manifest MACE.

Conclusion

In acute MI patients, plasma LCAT activity is decreased coinciding with increased MPO levels. Higher MPO but not lower LCAT activity prospectively predicts adverse cardiac outcome.     

Relationship between plasma apelin level and coronary collateral circulation

Objective

Coronary collaterals play a crucial role during an acute ischemic attack. Angiogenesis has an important role in the formation of coronary collateral vessels. Previously, it was shown that apelin is a potential angiogenetic factor. Thus, we aimed to investigate relationship between plasma apelin levels and coronary collateral circulation in patients with stable coronary artery disease.

Methods

Among patients who underwent coronary angiography with stable angina pectoris, patients with a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrop–Cohen classification. Patients with grade 2 or 3 collateral degree were included in good collateral group and patients with grade 0 or 1 collateral degree were included in poor collateral group.

Results

Plasma apelin level was significantly higher in good collateral group (0.69 ± 0.2 vs 0.59 ± 0.2 ng/dl, p < 0.001). Serum nitric oxide levels were similar between two groups. In multivariate regression analysis apelin [6.95 (1.46–33.15), p = 0.015] and presence of total occlusion [4.40 (1.04–18.62), p = 0.044] remained as independent predictors for good coronary collateral development.

Conclusions

Higher plasma apelin level was related to better coronary collateral development. Demonstration of favorable affects of apelin on good collateral development may lead to consider apelin in antiischemic treatment strategies in order to increase collateral development.     

Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia

Objectives

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused mainly by LDLR mutations. This study assessed the influence of the presence and type of LDLR mutation on lipid profile and the response to lipid-lowering therapy in Brazilian patients with heterozygous FH.

Methods

For 14 ± 3 months, 156 patients with heterozygous FH receiving atorvastatin were followed. Coding sequences of the LDLR gene were bidirectionally sequenced, and the type of LDLR mutations were classified according to their probable functional class.

Results

The frequencies of the types of LDLR mutations were: null-mutation (n = 40, 25.6%), defective-mutation (n = 59, 37.8%), and without an identified mutation (n = 57, 36.6%). Baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were higher in patients carrying a null mutation (9.9 ± 1.9 mmol/L, 7.9 ± 1.7 mmol/L), compared to those with a defective (8.9 ± 2.2 mmol/L, 7.0 ± 2.0 mmol/L), or no mutation (7.9 ± 1.9 mmol/L, 5.8 ± 1.9 mmol/L) (p < 0.001). After treatment, the proportion of patients attaining an LDL-C<3.4 mmol/L was significantly different among groups: null (22.5%), defective (27.1%), and without mutations (47.4%) (p = 0.02). The presence of LDLR mutations was independently associated with higher odds of not achieving the LDL-C cut-off (OR 9.07, 95% CI 1.41–58.16, p = 0.02).

Conclusions

Our findings indicate that the presence and type of LDLR mutations influence lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous FH. Thus, more intensive care with pharmacological therapeutics should be performed in patients who have a molecular analysis indicating the presence of a LDLR mutation.     

Non-invasive assessment of pulse wave velocity in mice by means of ultrasound images

Objective

Pulse wave velocity (PWV) is considered as a surrogate marker of arterial stiffness and could be useful for characterizing cardiovascular disease progression even in mouse models. Aim of this study was to develop an image process algorithm for assessing arterial PWV in mice using ultrasound images only and test it on the evaluation of age-associated differences in abdominal aorta PWV.

Methods

Ultrasound scans were obtained from ten adult (mean age: 5.5 months) and nine old (mean age: 15.5 months) wild type male mice (strain C57BL6) under gaseous anesthesia. For each mouse, instantaneous values of diameter and flow velocity were obtained from abdominal aorta B-mode and PW-Doppler, respectively. Single-beat mean diameter and velocity were calculated providing the velocity-diameter (lnD-V) loop. PWV values for both the early systolic phase (aaPWV) and the late systolic one (aaPWV_ls) were obtained from the slope of the corresponding linear parts of the loop. Relative distension (relD) was calculated from the mean diameter signal.

Results

aaPWV values for adult mice (1.91 ± 0.44 m/s) were significantly lower (p < 0.01) than those obtained for older ones (2.71 ± 0.63 m/s) and the same result was found for aaPWV_ls (2.68 ± 0.68 vs 3.67 ± 0.95 m/s; p < 0.05). relD measurements were significantly higher (p < 0.01) in adult (22.7% ± 5.2%) compared with older animal evaluations (15.8% ± 3.9%).

Conclusions

The proposed system discriminates well between age groups and supplies a non-invasive evaluation of anatomical and functional parameters of the mouse abdominal aorta. Since it provides a non-invasive PWV assessment from ultrasound (US) images only, it may offer a simple and useful system for evaluation of local vascular stiffness at other arterial site in the mouse, such as the carotid artery.     

Combination of plaque burden,wall shear stress,and plaque phenotype has incremental value for prediction of coronary atherosclerotic plaque progression and vulnerability

Aims

Large plaque burden, certain phenotypes, and low wall shear stress (WSS) are associated with adverse outcomes and high WSS with development of plaque vulnerability. We aimed to investigate the incremental value of the combination of plaque burden, WSS and plaque phenotype for prediction of coronary atherosclerotic plaque progression and vulnerability.

Methods

Twenty patients with CAD underwent baseline and 6-month follow-up coronary virtual histology-intravascular ultrasound (VH-IVUS) and computational fluid dynamics modeling for calculation of WSS. Low WSS was defined as <10 dynes/cm² and high WSS as ≥25 dynes/cm². Baseline plaque characteristics and WSS were related to plaque progression and vulnerability.

Results

In 2249 VH-IVUS frames analyzed, coronary segments with both plaque burden >40% and low WSS had significantly greater change in plaque area at follow-up (+0.68 ± 1.05 mm²), compared to segments with plaque burden >40% without low WSS (−0.28 ± 1.32 mm²) or segments with low WSS and plaque burden ≤40% (+0.05 ± 0.71 mm²) (p = 0.047). Among plaque phenotypes, pathologic intimal thickening (PIT) had the greatest increase in necrotic core (NC) area (p = 0.06) and greatest decrease in fibro-fatty (FF) area (p < 0.0001). At follow-up, compared to segments with either plaque burden >60%, PIT, or high WSS, those with a combination of plaque burden >60%, PIT, and high WSS developed greater increase in NC area (p = 0.002), greater decrease in FF (p = 0.004) and fibrous areas (p < 0.0001), and higher frequency of expansive remodeling (p = 0.019).

Conclusion

Combination of plaque burden, WSS, and plaque phenotype has incremental value for prediction of coronary plaque progression and increased plaque vulnerability in patients with non-obstructive CAD.