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Highlighted articles September

Volume 264 Issue September 2017

By Simona Negrini and Arnold von Eckardstein (Editor–in-Chief).

Peripheral artery disease (PAD) is a manifestation of atherosclerosis, which compromises quality of life and limits life expectancy both by itself and by its frequent confounding with coronary and cerebrovascular artery disease. PAD is increasingly targeted by research, first to improve its clinical management and second to exploit its accessibility for diagnostics already in the asymptomatic phase. This issue of Atherosclerosis contains several articles reporting on the validation of biomarkers of PAD, frequently towards clinical outcome either of PAD itself or associated diseases.

Issue highlights


    Highlighted articles

    Circulating soluble urokinase plasminogen activator receptor levels and peripheral arterial disease outcomes

    Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation associated with atherosclerosis. Tahhan et al. aimed at assessing whether suPAR levels are associated with prevalent peripheral arterial disease (PAD) and its adverse outcomes.

    SuPAR levels were measured in 5810 patients (77% with obstructive coronary artery disease [CAD]) undergoing cardiac catheterization. The presence of PAD was classified as carotid, lower/upper extremities, aortic and multisite disease. Multivariable logistic and Cox regression models were used to determine independent predictors of prevalent PAD and outcomes, including all-cause death, cardiovascular death and PAD-related events after adjustment for age, gender, race, body mass index, smoking, diabetes, hypertension, hyperlipidemia, renal function, heart failure history, and obstructive CAD.

    Plasma suPAR levels were 22.5% higher in patients with PAD compared to those without PAD. Plasma suPAR was higher in patients with more extensive PAD. After multivariable adjustment, suPAR was associated with prevalent PAD. In Cox survival analyses adjusted for clinical characteristics and medication regimen, suPAR remained an independent predictor of all-cause death, cardiovascular death and PAD-related events.

    Plasma suPAR level is predictive of prevalent PAD and of incident cardiovascular and PAD-related events. Whether SuPAR measurement can help screen, risk stratification, or monitoring of therapeutic responses in PAD requires further investigation.

    These results are discussed in depth in the editorial by Hoebaus et al.

    Differences in cardio-ankle vascular index in a general Mediterranean population depending on the presence or absence of metabolic cardiovascular risk factors

    Arterial stiffening is a marker of increased cardiovascular risk and a surrogate end-point for cardiovascular diseases. Results of meta-analyses have concluded that arterial stiffness, measured by means of aortic pulse wave velocity (PWV), is an independent predictive factor for cardiovascular events and mortality in different populations. Recently, a new arterial stiffness indicator has been proposed: the cardio-ankle vascular index (CAVI). CAVI integrates PWV and the stiffness parameter (β) in a single measurement.

    In this study, Martí-Lluch and colleagues analyzed 2613 subjects randomly selected in the Girona province (Catalonia, Spain) to assess differences in CAVI in individuals with metabolic cardiovascular risk factors or a previous history of vascular diseases compared to healthy individuals (free of risk factors and previous history of vascular diseases). Moreover, they described the proportion of CAVI≥9 depending on the cardiovascular risk category in both groups according to sex. This is the first time CAVI values are reported in a Mediterranean healthy population, as descriptive values of CAVI are mainly known for Eastern countries.

    The results show that CAVI mean differences between sexes and age categories in both groups follow the same pattern; healthy participants have lower CAVI than participants with metabolic risk factors. Moreover, high prevalence of abnormal CAVI is present in the low and moderate coronary risk categories.

    These results suggest that CAVI assessment to detect asymptomatic atherosclerosis could be a useful tool to improve cardiovascular risk stratification.

    Crural Index and extensive atherosclerosis of crural vessels are associated with long-term cardiovascular mortality in patients with symptomatic peripheral artery disease

    Limited data exist on the association of the anatomical distribution of atherosclerotic lesions and the extent of atherosclerosis at defined arterial segments with life expectancy. Wickström et al. recently presented a new classification of the extent of atherosclerosis in crural vessels and showed that Crural Index (CIx) was associated with mid-term survival of symptomatic peripheral artery disease (PAD) patients. In this study, the authors evaluate the significance of the extent of crural atherosclerosis on long-term cardiovascular mortality.

    Eight hundred eighty-seven consecutive patients with PAD, admitted for digital subtraction angiography at Turku University Hospital Department of Vascular Surgery (Turku, Finland) between January 1, 2009 and July 30, 2011, were retrospectively analysed. Each crural angiographic image was graded according to CIx criteria. Aorto-iliac and femoro-popliteal arterial segments were similarly graded according to modified TASC II criteria. CIx was used as the categorical variable for the extent of atherosclerosis in crural vessels for survival analysis. Survival was also evaluated with respect to which arterial segment was most severely affected. Causes of death were provided by the Cause of Death Registry of Statistics Finland.

    Altogether, 408 patients died during follow-up. The majority of deaths were due to cardiovascular causes. Cardiovascular mortality was strongly associated with a high CIx. In patients having the crural segment as the most severely affected arterial segment, cardiovascular mortality and overall mortality were significantly increased.

    High Crural Index and extensive crural vessel atherosclerosis are associated with long-term cardiovascular mortality, and both may serve as useful indicators of survival among patients with symptomatic PAD.

    Noninvasive assessment of subclinical atherosclerosis in persons with symptoms of depression

    Depression, a mood disorder characterized by persistent feelings of loss of interest along with a cluster of clinical symptoms, is a significant public health concern, affecting 350 million people worldwide, associated with an increased risk of cardiovascular disease (CVD). The World Health Organization estimates both depression and coronary artery disease to be the two major causes of disability-adjusted life years by year 2020. An early screening of patients with depression for subclinical atherosclerosis can provide assessment of CVD burden.

    In this review, Ali et al. performed an electronic search of MEDLINE database using PubMed and OvidSP. Subclinical atherosclerosis was identified by coronary artery calcium (CAC). A total of 24 studies were included in the analysis.

    Twelve of the 24 studies identified a positive association between depression and subclinical atherosclerosis. Ten studies found no significant association between depressive symptoms and coronary calcification, whereas two studies showed negative association.

    These results show that there is mixed evidence of the relationship between depression and CAC. CAC provides a non-invasive method for the assessment of CVD burden and can be used for risk stratification of patients. Subjects with higher CVD burden can be offered preventive treatment to halt progression of atherosclerosis.

    Circulating soluble receptor for advanced glycation end product: Cross-sectional associations with cardiac markers and subclinical vascular disease in older men with and without diabetes

    The soluble receptor for advanced glycation end products (sRAGE) has been implicated in diabetic vascular complications. Wannamethee et al. examined the association between sRAGE and cardiac markers [NT-proBNP and cardiac troponin T (cTnT)] and subclinical vascular markers in older men with and without diabetes.

    They performed a cross-sectional study of 1159 men aged 71–92 years with no history of cardiovascular disease (myocardial infarction, stroke, heart failure, coronary artery bypass graft operation or angioplasty). Prevalent diabetes included men with a doctor diagnosis of diabetes, men with fasting glucose ≥7 mmol/L or HbA1c ≥6.5%. Subclinical vascular measurements included carotid intima media thickness (cIMT), arterial stiffness [pulse wave velocity (PWV)], central aortic blood pressure and arterial wave reflections [central augmentation pressure (AP) and augmentation index (AIx)].

    sRAGE was strongly and positively associated with renal dysfunction in men with and without diabetes. sRAGE was significantly and positively associated with NT-proBNP (but not cTnT) and AP and AIx in both groups of men after adjustment for CVD risk and metabolic risk markers, renal function and inflammation. However, no association was seen between sRAGE and central aortic blood pressure, cIMT or arterial stiffness as determined by PWV in either group.

    Higher plasma sRAGE was associated with increased NT-proBNP and markers of arterial wave reflections in men both with and without diabetes. Whether sRAGE predicts worsening cardiac dysfunction and heart failure needs to be tested.

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