Reversion of the Inflammatory Markers in Patients With Chronic Limb-Threatening Ischemia.

BACKGROUND: Peripheral artery disease is characterized by an intense inflammatory process that can be associated with a higher mortality rate, particularly in chronic limb-threatening ischemia (CLTI). This study aims to compare the evolution of inflammatory markers between patients with claudication with those with CLTI at 3, 6, and 12 months. METHODS AND RESULTS: An observational, single-center, and prospective study was conducted. A total of 119 patients with peripheral artery disease (65 with claudication and 54 with CLTI) were observed and inflammatory markers collected at admission and 3, 6, and 12 months. At admission, patients with CLTI, when compared with patients with claudication, had significantly higher serum levels of C-reactive protein and fibrinogen (positive acute-phase proteins) and lower serum level of albumin, total cholesterol, and high-density lipoprotein (negative acute-phase proteins): C-reactive protein (g/dL), 2.90 (25th-75th percentile, 2.90-4.90) versus 6.80 (25th-75th percentile, 2.90-53.26) (P=0.000); fibrinogen (mg/dL), 293.00 (25th-75th percentile, 269.25-349.00) versus 415.50 (25th-75th percentile, 312.00-615.75) (P=0.000); total cholesterol (mg/dL), 161.79±95% [152.74-170.85] versus 146.42%±95% [135.30-157.53] (P=0.034); high-density lipoprotein (mg/dL), 50.00 (25th-75th percentile, 41.00-60.00) versus 37.00 (25th-75th percentile, 30.00-45.50) (P=0.000); albumin (g/dL): 4.00 (25th-75th percentile, 3.70-4.20) versus 3.60 (25th-75th percentile, 3.10-4.00) (P=0.003). The association between CLTI and total cholesterol was lost after adjusting for confounders. Three months after the resolution of the CLTI, there was an increase in the levels of negative acute-phase proteins and a decrease in positive acute-phase proteins. These inflammatory proteins did not register an evolution in patients with claudication. The differences in the inflammatory proteins between groups disappeared at 6 months. CONCLUSIONS: CLTI has an inflammatory environment that can be partially reverted after resolution of the ischemic process, emphasizing the importance of timely intervention.

The Association of Metabolic Dysfunction and Mood Across Lifespan Interacts With the Default Mode Network Functional Connectivity.

Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study. Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied. Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmetabolism, lipids imbalance, and blood pressure. Using multiple linear regression models, this study observed that metabolic dysfunction, glucose dysmetabolism, and lipids imbalance were linearly associated with depressive mood, and the association with obesity was U-shaped. The association of metabolic dysfunction, obesity, and glucose dysmetabolism with depressive mood is positive for the younger individuals in our sample and vanishes with aging. The FC of the right superior temporal gyrus with the DMN correlated with both obesity and depressive mood. In participants with higher obesity scores, FC increased with higher GDS scores, while in those with lower GDS scores, FC decreased. Age and blood pressure were associated with a more complex pattern of association between FC of the right supramarginal gyrus and GDS score. Conclusion: The association of metabolic dysfunction with depressive mood is influenced by age and relates with differential patterns of DMN-FC. The combination of the effects of age, mood, and metabolic dysfunction is likely to explain the heterogeneity of DMN-FC, which deserves further investigation with larger and longitudinal studies.

Early Vascular Ageing (EVA): Definitions and Clinical Applicability.

Arterial stiffness has been accumulating evidence as an intermediate cardiovascular endpoint. It has been established as an independent risk marker for cardiovascular disease, and reflects the dissociation between chronologic and biologic age of large arteries-attributing earlier the risk that a normal vascular ageing process had installed to occur several years later. The concept of Early Vascular Ageing (EVA) is developed to establish primordial prevention, identifying individuals whose ageing path has been accelerated either by inherent features, interaction with the environment or arterial exposure to several types of insults that evolve to medial layer morphological changes. Understanding the pathophysiology of vascular ageing, its consequences and therapeutic opportunities is therefore an advantage that could be translated in time of prevention and survival free of cardiovascular disease. As the EVA construct is advancing, new features appear as interesting to better translate it into clinical practice.

Metabolic syndrome across Europe: different clusters of risk factors.

BACKGROUND: Metabolic syndrome (MetS) remains a controversial entity. Specific clusters of MetS components - rather than MetS per se - are associated with accelerated arterial ageing and with cardiovascular (CV) events. To investigate whether the distribution of clusters of MetS components differed cross-culturally, we studied 34,821 subjects from 12 cohorts from 10 European countries and one cohort from the USA in the MARE (Metabolic syndrome and Arteries REsearch) Consortium. METHODS: In accordance with the ATP III criteria, MetS was defined as an alteration three or more of the following five components: elevated glucose (G), fasting glucose ≥110 mg/dl; low HDL cholesterol, < 40mg/dl for men or <50 mg/dl for women; high triglycerides (T), ≥150 mg/dl; elevated blood pressure (B), ≥130/≥85 mmHg; abdominal obesity (W), waist circumference >102 cm for men or >88 cm for women. RESULTS: MetS had a 24.3% prevalence (8468 subjects: 23.9% in men vs. 24.6% in women, p < 0.001) with an age-associated increase in its prevalence in all the cohorts. The age-adjusted prevalence of the clusters of MetS components previously associated with greater arterial and CV burden differed across countries (p < 0.0001) and in men and women (p < 0.0001). In details, the cluster TBW was observed in 12% of the subjects with MetS, but was far more common in the cohorts from the UK (32.3%), Sardinia in Italy (19.6%), and Germany (18.5%) and less prevalent in the cohorts from Sweden (1.2%), Spain (2.6%), and the USA (2.5%). The cluster GBW accounted for 12.7% of subjects with MetS with higher occurrence in Southern Europe (Italy, Spain, and Portugal: 31.4, 18.4, and 17.1% respectively) and in Belgium (20.4%), than in Northern Europe (Germany, Sweden, and Lithuania: 7.6, 9.4, and 9.6% respectively). CONCLUSIONS: The analysis of the distribution of MetS suggested that what follows under the common definition of MetS is not a unique entity rather a constellation of cluster of MetS components, likely selectively risky for CV disease, whose occurrence differs across countries.

The rationale/design of the Guimarães/Vizela study: a multimodal population-based cohort study to determine global cardiovascular risk and disease.

BACKGROUND: Cardiovascular disease and dementia are growing medical and social problems in aging societies. Appropriate knowledge of cardiovascular disease and cognitive decline risk factors (RFs) are critical for global CVR health preventive intervention. Many epidemiological studies use case definition based on data collected/measured in a single visit, a fact that can overestimate prevalence rates and distant from clinical practice demanding criteria. Portugal displays an elevated stroke mortality rate. However, population's global CV risk characterization is limited, namely, considering traditional/nontraditional RF and new intermediate phenotypes of CV and renal disease. Association of hemodynamic variables (pulse wave velocity and central blood pressure) with global CVR stratification, cognitive performance, and kidney disease are practically inexistent at a dwelling population level. STUDY DESIGN AND METHODS: After reviewing published data, we designed a population-based cohort study to analyze the prevalence of these cardiovascular RFs and intermediate phenotypes, using random sampling of adult dwellers living in 2 adjacent cities. Strict definition of phenotypes was planned: subjects were observed twice, and several hemodynamic and other biological variables measured at least 3 months apart. RESULTS: Three thousand thirty-eight subjects were enrolled, and extensive data collection (including central and peripheral blood pressure, pulse wave velocity), sample processing, and biobank edification were carried out. One thousand forty-seven cognitive evaluations were performed. CONCLUSIONS: Seeking for CV risk reclassification, early identification of subjects at risk, and evidence of early vascular aging and cognitive and renal function decline, using the strict daily clinical practice criteria, will lead to better resource allocation in preventive measures at a population level.

Decreasing arterial aging by controlling blood pressure levels and hypertension: a step forward.

Arterial aging, characterized by arterial stiffening that is clinically evaluable as aortic pulse wave velocity, is risky for CV events, disability, and loss of cognitive function. Today the only adopted strategy to decrease arterial aging/ arterial stiffness is represented by decreasing BP. Selective antihypertensive drug classes (calcium channel blockers, converting enzyme inhibitors, angiotensin type 1 receptor antagonists) showed a beneficial effect on the arterial wall and on both large and small arteries over and above the reduction in BP levels. Still, the lower the better paradigm seems only to expose older subjects to higher rate of side effects, that via hypotension result in even transient organ hypoperfusion. This vicious circle may be particularly detrimental for cerebral district and, thus, for cognitive impairment onset and progression until dementia.