Biomarkers and Genetics in Peripheral Artery Disease

Hazarika, Surovi; Annex, Brian H.

doi:10.1373/clinchem.2016.263798

Cited by 40 publications

(31 citation statements)

References 95 publications

(104 reference statements)

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“…We replicated the statistical interaction of the two SNPs for CAD in two independent cohorts ( Table 7), both of which are other manifestations of atherosclerosis in coronary arteries in which Lp(a) plasma levels affect risk 25,26 .…”

Section: The Few Double Homozygote [T/t] -[A/a]mentioning

confidence: 75%

Cis-epistasis at the LPA locus and risk of coronary artery disease

Zeng

Mirza‐Schreiber

Lamina

et al. 2019

Preprint

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Identification of epistasis affecting complex human traits has been challenging. Focusing on known coronary artery disease (CAD) risk loci, we explore pairwise statistical interactions between 8,068 SNPs from ten CAD genome-wide association studies (n=30,180). We discovered rs1800769 and rs9458001 in the vicinity of the LPA locus to interact in modulating CAD risk (P=1.75×10−13). Specific genotypes (e.g., rs1800769 CT) displayed either significantly decreased or increased risk for CAD in the context of genotypes of the respective other SNP (e.g., rs9458001 GG vs. AA). In the UK Biobank (n=450,112) significant interaction of this SNP pair was replicated for CAD (P=3.09×10−22), and was also found for aortic valve stenosis (P=6.95×10−7) and peripheral arterial disease (P=2.32×10−4). Identical interaction patterns affected circulating lipoprotein(a) (n=5,953; P=8.7×10−32) and hepatic apolipoprotein(a) (apo(a)) expression (n=522, P=2.6×10−11). We further interrogated potential biological implications of the variants and propose a mechanism explaining epistasis that ultimately may translate to substantial cardiovascular risks.

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Section: The Few Double Homozygote [T/t] -[A/a]mentioning

confidence: 75%

Cis-epistasis at the LPA locus and risk of coronary artery disease

Zeng

Mirza‐Schreiber

Lamina

et al. 2019

Preprint

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“…T2DM patients with PAD have a higher risk of cardiovascular complications than T2DM patients without peripheral vascular involvement [2]. Despite multiple therapeutic approaches and multidisciplinary management, de nite biomarkers, useful to stratify the risk for T2DM patients with PAD and CLTI are not available [24,25]. Regarding follow-up after revascularization, even less clear evidence is available [26].…”

Section: Discussionmentioning

confidence: 99%

Association between Omentin-1 and Major Cardiovascular Events After Lower Extremity Endovascular Revascularization in Diabetic Patients: A Prospective Cohort Study

Biscetti

Nardella

Rando

et al. 2020

Preprint

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Background: Cardiovascular complications represent the major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM) patients. In particular, peripheral artery disease (PAD) represents a frequent T2DM vascular complication and a risk factor for the development of major adverse cardiovascular events (MACE). Among adipokines, Omentin-1 serum levels are reduced in T2DM patients with PAD and are inversely related to disease severity.Objective: To study the relationship between Omentin-1 levels, at baseline, with outcomes after endovascular procedures in T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We enrolled for our prospective non-randomized study, 207 T2DM patients with PAD and CLTI, requiring revascularization. Omentin-1 serum levels were collected before revascularization and patients incidence outcomes were evaluated at 1, 3, 6 and 12 months.Results: Omentin-1 was reduced in patients with more severe disease (27.24 ± 4.83 ng/mL vs 30.82 ± 5.48 ng/mL, p < 0.001). Overall, 84 MACE and 96 major adverse limb events (MALE) occurred during the 12-month follow-up. We observed that Omentin-1 levels were lower in patients with MACE (26.02 ± 4.05 ng/mL vs 31.33 ± 5.29 ng/mL, p < 0.001) and MALE (26.67 ± 4.21 ng/mL vs 31.34 ± 5.54 ng/mL, p < 0.001). The association between Omentin-1, MACE and MALE remained significant after adjusting for major risk factors in a multivariate analysis. Receiver operating characteristics (ROC) curve using Omentin-1 levels predicted incidence events (area under the curve = 0.80).Conclusions: We demonstrated that reduced Omentin-1 levels, at baseline, are related with worse vascular outcomes in T2DM patients with PAD and CLTI undergoing an endovascular procedure.

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“…В проведенном нами исследовании пациенты с СД2 отличались статистически значимо меньшими значениями ИЛ-1β и ИЛ-6, а также большей тяжестью атеросклероза периферических артерий. При этом были выявлены прямые корреляционные взаимосвязи уровней провоспалительных цитокинов и ультрасонографических маркеров тяжести атеросклероза, что находится в соответствии с ранее опубликованными работами [14,15].…”

Section: резюме основного результата исследованияunclassified

“…В ряде исследований установлены взаимосвязи таких цитокинов, как ИЛ-1, ИЛ-6, ИЛ-8, вчСРБ и различных клинических особенностей артерий нижних конечностей [14]. Известна прогностическая ценность ИЛ-6 в отношении снижения лодыжечно-плечевого индекса (ЛПИ) в течение 5 и 12 лет наблюдения, а также ИЛ-6 и вчСРБ -в отношении снижения функционального статуса пациентов [15].…”

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Peripheral arterial disease and indicators of low-grade inflammation in patients with coronary artery disease and type 2 diabetes mellitus

et al. 2018

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BACKGROUND: The study of low-grade inflammation in patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular diseases is a pressing problem. A deeper understanding of the cascade of inflammatory reactions, possibly mediating the severe atherosclerotic lesions of various vascular pools in patients with diabetes, has the potential to introduce more sophisticated diagnostic and therapeutic approaches into practice. AIM: To study the interrelation of low-grade inflammation and atherosclerosis of peripheral arteries in patients with coronary artery disease (CAD) and T2DM. MATERIALS AND METHODS: The study included 137 patients (77 men and 60 women) with CAD. The average age of patients was 62.0 (57.066.0) years. The first group included 67 patients with CAD and T2DM, and the second group included 70 patients with CAD. Low-grade inflammation was assessed by the levels of high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10 and TNF-. All patients underwent duplex scanning of carotid arteries and lower extremity arteries (LEAs). RESULTS: Patients with CAD and T2DM showed significantly greater values of stenosis of carotid arteries and LEAs. Direct correlation was revealed between markers of inflammation and the degree of stenosis of the femoral and tibial arteries, as well as the intima-media thickness of the carotid and femoral arteries. In the group of patients with T2DM, the value of IL-1 was 2.04 (0.982.52) pg/mL, which was significantly less than 2.43 (1.843.19) pg/mL for patients in the second group (p = 0.010). The values of IL-6 were also significantly lower in the first group of patients, at 1.84 (0.734.41) pg/mL vs. 3.73 (2.2710.2) pg/mL in the first and second groups, respectively (p = 0.008). The dose of metformin was inversely correlated with the level of IL-6 (r = 0.314, p = 0.003). CONCLUSIONS: Patients with CAD and T2DM compared with patients without diabetes had significantly greater values of stenosis of peripheral arteries. The levels of IL-1 and IL-6 in the group of patients with CAD and T2DM were significantly lower in comparison with patients without diabetes. The dose of metformin was inversely correlated with the level of IL-6.

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Biomarkers and Genetics in Peripheral Artery Disease

Cited by 40 publications

References 95 publications

Cis-epistasis at the LPA locus and risk of coronary artery disease

Cis-epistasis at the LPA locus and risk of coronary artery disease

Association between Omentin-1 and Major Cardiovascular Events After Lower Extremity Endovascular Revascularization in Diabetic Patients: A Prospective Cohort Study

Peripheral arterial disease and indicators of low-grade inflammation in patients with coronary artery disease and type 2 diabetes mellitus

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