Prevalent peripheral arterial disease and inflammatory burden

Abstract

BackgroundStrong evidence implicates inflammation in the development of atherosclerotic heart disease but less is known about peripheral arterial disease (PAD). Our objective was to test the hypothesis that a composite index of inflammatory burden is associated with PAD.MethodsCross-sectional analysis of a randomly-selected group of 903 community-dwelling men in the MrOS cohort recruited between 2000 and 2002. Using blood samples, we measured seven cytokines and related these levels to prevalent PAD (ankle-brachial index (ABI) <0.9) both individually and as part of an “inflammatory burden score” (a composite sum of the number of pro-inflammatory cytokines in the highest quartile).ResultsOverall, 6.75% of men had ABI <0.9. The odds of prevalent PAD were higher in men with the highest quartile (Q4) levels of interleukin-6 multivariable (MV) adjusted (odds ratio (OR) =3.95 (95% CI, 1.4–11.3), tumor necrosis factor alpha OR = 4.44 (95% confidence interval (CI), 1.5–12.8), and C-reactive protein OR = 3.63 (95% CI, 1.4–9.4) compared to men in Q1. The magnitude of the association of these cytokines with PAD was similar to the effect of being 10 years older, OR = 2.41 (95% CI, 1.16–3.7). These significant effects persisted after additional MV adjustment for smoking except for CRP. Men with the highest inflammatory burden score (≥3) had 3.6 (95% CI, 1.5–8.7) increased odds of PAD, p trend = 0.03. After smoking adjustment the linear trend was borderline statistically significant (p trend = 0.10).ConclusionInflammatory burden is associated with prevalent PAD, an association similar to aging 10 years. The inflammatory effects of smoking contributes to the underlying association between inflammation and PAD.

Oxidative Stress and Arterial Dysfunction in Peripheral Artery Disease

“…It has also been shown that NOX2-derived ROS production in the extracellular space is in fact increased in vascular disease [ 23 ]. Atherogenic molecules such as tumor necrosis factor α (TNF-α), cholesterol, and homocysteine, which have all been shown to be significantly elevated in PAD [ 102 , 103 ], increase endothelial NOX2 expression [ 23 ]. Furthermore, these molecules lead to clustering of lipid raft domains, which causes NOX2 aggregates to form in the plasma membrane [ 23 ].…”

Differences in coronary plaque characteristics between patients with and those without peripheral arterial disease

“…Macrophages are key inflammatory cells that are involved at every phase of atherosclerosis, from its genesis to plaque rupture or erosion. Recent studies found that PAD was associated with increased levels of local proinflammatory cytokines, some of which were known to be linked to CAD progression [20][21][22]. A previous study showed that the severity of coronary atherosclerosis was related to the degree of inflammatory response in the affected PAD limb [23].…”

Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option

“…It is rapidly emerging as a significant global socio-economic burden and currently affects over 202 million people ( 2 ). PAD is associated with significant cardiovascular morbidity and mortality ( 3 ), plus a severely diminished quality of life ( 4 ). PAD is most commonly a result of atherosclerosis and, as such, risk factors for the development of the disease include smoking, diabetes mellitus (DM), hypertension ( 5 ), and advanced age ( 6 ).…”