[Chronic obstructive pulmonary disease and cardiovascular disease].
ABSTRACT In the last decade, various studies have suggested that chronic obstructive pulmonary disease (COPD) could favor the development of ischemic heart disease. Several observational and case-control studies have confirmed that patients with COPD have a higher risk of cardiovascular disorders. However, this increased risk could be largely explained by a greater prevalence of classical risk factors. Currently, there are no data to indicate a causal relation between COPD and cardiovascular disease and the concept of systemic inflammation as a common pathogenic mechanism has not been demonstrated. Equally, there is insufficient evidence to conclude that some drugs, such as statins or inhaled corticoids, could decrease cardiovascular risk in patients with COPD by reducing systemic inflammation. Currently, these drugs should only be recommended if patients show specific indications for their use.
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Article: Comorbidities and Polypharmacy[Show abstract] [Hide abstract]
ABSTRACT: Heart failure (HF) is predominantly a disease that affects the elderly population, a cohort in which comorbidities are common. The majority of comorbidities and the degree of their severity have prognostic implications in HF. Polypharmacy in HF is common, has increased throughout the past 2 decades, and may pose a risk for adverse drug interactions, accidental overdosing, or medication nonadherence. Polypharmacy, in particular in the elderly, is rarely assessed in traditional clinical trials, highlighting a need for entirely novel HF research strategies.Heart Failure Clinics 04/2014; 10(2):367–372. · 1.41 Impact Factor
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ABSTRACT: Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5×10-4, per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD.PLoS ONE 08/2014; 9(8):e104082. · 3.53 Impact Factor
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ABSTRACT: Cigarette smoking is an important risk factor for chronic obstructive pulmonary disease (COPD), yet its pathogenic mechanisms are not yet fully understood. Endothelial dysfunction is known to be involved in the pathogenesis of COPD. A detailed understanding of the mechanism involved in its progression would have a substantial impact on the optimization and development of treatment strategies. Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cells (HPMECs). Overexpression of SIRT4 significantly inhibits CSE-induced mononuclear cell adhesion to HPMECs. Consistently, we found that overexpression of SIRT4 attenuates the induction of vascular cell adhesion molecule 1 (VCAM-1) and E-selectin. Importantly, SIRT4 was found to negatively regulate CSE-induced NF-κB activation via inhibiting the degradation of IκBα. Moreover, we also found that proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6, the downstream target genes of NF-κB, are also inhibited by overexpression of SIRT4. These results suggest that SIRT4 protects HPMECs exposed to CSE stress via a mechanism that may involve the NF-κB pathway. Strategies based on the enhancement of SIRT4 may prove to be beneficial in the treatment of cigarette smoking caused COPD.Toxicology Letters 03/2014; · 3.36 Impact Factor