Associations between Various Inflammatory Markers and Carotid Findings in a Voluntary Asymptomatic Population Sample.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5-67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms.

Short-Term Blood Pressure Variability among Young Adults at High or Low Risk for Depression.

Background: Depression has been shown to have adverse effects on blood pressure (BP) and is associated with high blood pressure variability (BPV). In turn, high short-term BPV has been related to eventual cardiovascular risk. But it is not clear how early in adulthood the detrimental effects of depression on BPV may be discerned, if being at high risk for depression also compromises BPV, and whether the clinical features of depression moderate its adverse effects. We investigated these three issues among young adults using an office-like setting. Methods: In total, 218 subjects with a history of childhood-onset major depressive episodes (probands), 206 never-depressed full biological siblings of the probands (high-risk siblings), and 166 emotionally healthy unrelated controls received a psychiatric evaluation and three standardized-sitting BP measurements 5 min apart. Short-term BPV was defined as the maximum difference between measures (range) for each case. The statistical methods included analyses of variance/covariance, chi-square tests, and multiple regression. Results: Systolic and diastolic BP decreased over consecutive measurements (p < 0.001). After controlling for age, the probands, siblings, and controls did not differ significantly in terms of BPV. However, the number of lifetime depressive episodes did predict the diastolic BP range (p = 0.005): probands with the highest number of depressive episodes had the largest short-term diastolic BPV. Conclusions: On a group level, the adverse effects on BPV of having experienced or being at high risk for depression are not yet evident during young adulthood. However, the number of major depressive episodes, which is an index of lifetime depression burden, predicts higher BPV. Thus, BPV monitoring for young adults with clinical depression histories could be part of an early intervention program to reduce the risk of eventual cardiovascular disease.

Growth and differentiation factor-15: A link between inflammaging and cardiovascular disease.

Age-related disorders are closely linked to the accumulation of senescent cells. The senescence-associated secretory phenotype (SASP) sustains and progresses chronic inflammation, which is involved in cellular and tissue dysfunction. SASP-related growth and differentiation factor-15 (GDF-15) is an immunoregulatory cytokine that is coupled to aging and thus may have a regulatory role in the development and maintenance of atherosclerosis, a major cause of cardiovascular disease (CVD). Although the effects of GDF-15 are tissue-specific and dependent on microenvironmental changes such as inflammation, available data suggest that GDF-15 has a significant role in CVD. Thus, GDF-15 is a promising biomarker and potential therapeutic target for atherosclerotic CVD.

Effect of Sex, Age, and Cardiovascular Risk Factors on Aortoiliac Segment Geometry.

Background: To investigate the geometry of the aortoiliac (AI) segment and its correlation with sex, age, and cardiovascular (CV) risk factors. Methods: Abdominal and pelvic CTA/MRA scans of 204 subjects (120 males; median age: 53 [IQR, 27-75] years) without AI steno-occlusive disease or scoliosis were retrospectively analyzed. The participants were enrolled consecutively, ensuring the representation of each age decade. An in-house written software was developed to assess AI elongation using the tortuosity index (TI) and absolute average curvature (AAC). Aortic bifurcation angle, common iliac artery (CIA) take-off and planarity angles, bifurcation asymmetry, and deviation from optimal bifurcation were calculated and evaluated. Demographic data, CV risk factors, and medical history were collected from electronic health records. Results: The elongation of the iliac arteries was more pronounced in males (TI: left CIA, p = 0.011; left EIA, p < 0.001; right CIA, p = 0.023; right EIA, p < 0.001; AAC: left EIA, p < 0.001; right EIA, p = 0.001). Age significantly influenced TI and AAC in all AI segments (all p < 0.001), but was also positively associated with the aortic bifurcation angle (p < 0.001), both CIA planarities (left, p < 0.001; right, p = 0.002), aortic bifurcation asymmetry (p = 0.001), and radius discrepancy (p < 0.001). Significant positive correlations were found between infrarenal aortic TI/AAC and chronic kidney disease (CKD) (p = 0.027 and p = 0.016), AAC of both CIAs and hypertension (left, p = 0.027; right, p = 0.012), right CIA take-off angle and CKD (p = 0.031), and left CIA planarity and hyperlipidemia (p = 0.006). Conclusion: Sex, age, and CV risk factors have a significant effect on the geometry of the AI segment.

Association of growth and differentiation factor-15 with coronary artery calcium score and ankle-brachial index in a middle-aged and elderly Caucasian population sample free of manifest cardiovascular disease.

Growth and differentiation factor-15 (GDF-15) is a stress-associated cytokine of the transforming growth factor-ß superfamily. The inflammatory and angiogenic effects of GDF-15 in atherosclerosis are controversial, and its correlation with the long asymptomatic phase of the disease is not well understood. Coronary artery calcium score (CACS) and ankle-brachial index (ABI) are sensitive markers of subclinical atherosclerosis. To date, only a few studies have examined the impact of GDF-15 on coronary artery calcification, and the association between GDF-15 and ABI has not been evaluated. Therefore, we aimed to investigate the possible relationship between serum GDF-15 concentrations and CACS and ABI in a Caucasian population sample of middle-aged (35-65 years) and elderly (> 65 years) people. In addition to recording demographic and anthropometric characteristics, atherosclerotic risk factors, and laboratory tests including serum HDL-cholesterol, LDL-cholesterol, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP); GDF-15 level, cardiac computed tomography, and ABI measurements were also performed. A total of 269 asymptomatic individuals (men, n = 125; median age, 61.5 [IQR, 12.7] years) formed the basis of this study. Participants were divided into two groups according to their age (middle-aged, n = 175 and elderly, n = 94). Hypertension and diabetes mellitus were significantly more prevalent and CACS values and HbA1c, NT-proBNP, and GDF-15 levels were significantly higher (all p < 0.001) in the elderly group compared to the middle-aged group. Multivariate ridge regression analysis revealed a significant positive association between GDF-15 and CACS (middle-aged group: ß = 0.072, p = 0.333; elderly group: ß = 0.148, p = 0.003), and between GDF-15 and ABI (middle-aged group: ß = 0.062, p = 0.393; elderly group: ß = 0.088, p = 0.041) only in the elderly group. Our results show that GDF-15 is not only a useful biomarker of inflammation but can also predict early signs of asymptomatic atherosclerosis, especially in elderly people with chronic systemic inflammation associated with aging (inflammaging).

Metabolic syndrome among young adults at high and low familial risk for depression.

BACKGROUND: Our study examined whether the early-onset depression phenotype among young adults (probands) is associated with the metabolic syndrome (MetS) and its components, and if MetS characterizes unaffected but high-risk siblings of probands. METHODS: We studied three groups of young adults (Mage = 25 years, s.d. = 3.84 years): probands with histories of childhood onset depression - i.e. early-onset phenotype - (n = 293), their unaffected siblings (high-risk siblings, n = 273), and healthy controls (n = 171). Participants completed a full psychiatric interview, physical and laboratory assessments, and self-rating scales. MetS was defined using the criteria of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (). RESULTS: Early-onset depression phenotype and being a high-risk sibling were associated with higher MetS composite scores relative to that of controls, but did not differ from one another. With regard to MetS components: Probands and siblings had similarly larger waist circumference and lower HDL than did controls, while siblings and controls had lower triglyceride levels than did probands but did not differ from one another. Groups did not differ on glucose levels and SBP. CONCLUSIONS: Our study extends the literature on the association between MetS and depression and underscores the importance of depression phenotypes: failure to account for the clinical heterogeneity of depression may partly underlie the inconsistent findings regarding its relation to MetS. The results also suggest that, in depression-prone populations, MetS may predate and possibly function as a risk factor for eventual depression.

Long-term prognostic value of left atrial longitudinal strain in an elderly community-based cohort.

Despite the well-known importance of left atrial (LA) mechanics in diastolic function, data are scarce regarding the prognostic power of LA longitudinal strain and its potential added value in the risk stratification of an elderly population. Accordingly, our aim was to determine the long-term prognostic importance of 2D speckle-tracking echocardiography-derived peak atrial longitudinal strain (PALS) in a community-based screening sample. Three hundred and fourteen volunteers were retrospectively identified from a population-based screening program (mean age 62 ± 11 years; 58% female) with a median follow-up of 9.5 years. All subjects who participated in the screening program underwent 2D echocardiography to measure left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and PALS, as well as low-dose cardiac CT to determine the Agatston score. The primary endpoint was all-cause mortality. Thirty-nine subjects (12.4%) met the primary endpoint. Subjects with adverse outcomes had significantly lower LV GLS (dead vs. alive; - 19.2 ± 4.3 vs. - 20.6 ± 3.5%, p < 0.05) and PALS (32.3 ± 12.0 vs. 41.8 ± 14.2%, p < 0.001), whereas LV EF did not show a difference between the two groups (51.1 ± 7.0 vs. 52.1 ± 6.2, %, p = NS). By multivariable Cox regression analysis, PALS was found to be a significant predictor of adverse outcomes independent of LV GLS, and Agatston and Framingham scores. In subjects with PALS values below the standard cut-off of 39%, the risk of all-cause mortality was almost 2.5 times higher (hazard ratio: 2.499 [95% confidence interval: 1.334-4.682], p < 0.05). Beyond the assessment of LV EF and LV GLS, PALS offers incremental value in cardiovascular risk stratification in a community-based elderly cohort. PALS was found to be a significant and independent predictor of long-term mortality among other classical cardiovascular risk estimators.

Amputation and mortality rates of patients undergoing upper or lower limb surgical embolectomy and their predictors.

PURPOSE: To provide information on the outcomes of upper and lower limb surgical embolectomies and the factors influencing amputation and mortality. METHODS: A retrospective, single-center analysis of 347 patients (female, N = 207; male, N = 140; median age, 76 years [interquartile range {IQR}, 63.2-82.6 years]) with acute upper or lower limb ischemia due to thromboembolism who underwent surgery between 2005 and 2019 was carried out. Patient demographics, comorbidities, medical history, the severity of acute limb ischemia (ALI), preoperative medication regimen, embolus/thrombus localization, procedural data, in-hospital complications/adverse events and their related interventions, and 30-day mortality were reviewed in electronic medical records. Statistical analysis was performed using the Mann-Whitney U test and Fisher's exact test; in addition, univariate and multivariate logistic regression was conducted. RESULTS: The embolus/thrombus was localized to the upper limb in 134 patients (38.6%) and the lower limb in 213 patients (61.4%). The median length of hospital stay was 3.8 days (IQR, 2.1-6.6 days). The in-hospital major amputation rates for the upper limb, lower limb, and total patient population were 2.2%, 14.1%, and 9.5%, respectively, and the in-hospital plus 30-day mortality rates were 4.5%, 9.4%, and 7.5%, respectively. In patients with lower limb embolectomy, the predictor of in-hospital major amputation was the time between the onset of symptoms and embolectomy (OR, 1.78), while the predictor of in-hospital plus 30-day mortality was previous stroke (OR, 7.16). In the overall patient cohort, there were two predictors of in-hospital major amputation: 1) the time between the onset of symptoms and embolectomy (OR, 1.92) and 2) compartment syndrome (OR, 3.51). CONCLUSION: Amputation and mortality rates after surgical embolectomies in patients with ALI are high. Patients with prolonged admission time, compartment syndrome, and history of stroke are at increased risk of limb loss or death. To avoid amputation and death, patients with ALI should undergo surgical intervention as soon as possible and receive close monitoring in the peri- and postprocedural periods.

Short- and Mid-Term Outcomes of Stenting in Patients with Isolated Distal Internal Carotid Artery Stenosis or Post-Surgical Restenosis.

The aim was to evaluate the outcome of stenting in patients with isolated distal internal carotid artery (ICA) stenosis or post-surgical restenosis, as no data are currently available in the literature. Sixty-six patients (men, N = 53; median age: 66 [IQR, 61-73] years) with ≥50% distal ICA (re)stenosis were included in this single-center retrospective study. The narrowest part of the (re)stenosis was at least 20 mm from the bifurcation in all patients. Patients were divided into two etiological groups, atherosclerotic (AS, N = 40) and post-surgical restenotic (RES, N = 26). Postprocedural neurological events were observed in two patients (5%) in the AS group and in two patients (7.7%) in the RES group. The median follow-up time was 40 (IQR, 18-86) months. Three patients (7.5%) in the AS group had an in-stent restenosis (ISR) ≥ 50%, but none in the RES group. Three patients (7.5%) in the AS group and seven patients (26.9%) in the RES group died. None of the deaths in the RES group were directly related to stenting itself. The early neurological complication rate of stenting due to distal ICA (re)stenoses is acceptable. However, the mid-term mortality rate of stenting for distal ICA post-surgical restenoses is high, indicating the vulnerability of this subgroup.

3D culturing of human pluripotent stem cells-derived endothelial cells for vascular regeneration.

Rationale: Human induced pluripotent stem cell-derived endothelial cells can be candidates for engineering therapeutic vascular grafts. Methods: Here, we studied the role of three-dimensional culture on their characteristics and function both in vitro and in vivo. Results: We found that differentiated hPSC-EC can re-populate decellularized biomatrices; they remain viable, undergo maturation and arterial/venous specification. Human PSC-EC develop antifibrotic, vasoactive and anti-inflammatory properties during recellularization. In vivo, a robust increase in perfusion was detected at the engraftment sites after subcutaneous implantation of an hPSC-EC-laden hydrogel in rats. Histology confirmed survival and formation of capillary-like structures, suggesting the incorporation of hPSC-EC into host microvasculature. In a canine model, hiPSC-EC-seeded onto decellularised vascular segments were functional as aortic grafts. Similarly, we showed the retention and maturation of hiPSC-EC and dynamic remodelling of the vessel wall with good maintenance of vascular patency. Conclusions: A combination of hPSC-EC and biomatrices may be a promising approach to repair ischemic tissues.