Risk Factors for Subclinical Carotid Atherosclerosis Among Current Smokers

University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Preventive Cardiology 09/2010; 13(4):166-71. DOI: 10.1111/j.1751-7141.2010.00068.x
Source: PubMed


This study characterized the determinants of carotid atherosclerosis in a large contemporary sample of current smokers. Associations between risk factors, carotid intima-media thickness (CIMT), and carotid plaque presence were determined by multivariable regression. Participants included 1504 current smokers (58% female) who were a median (interquartile range) of 44.7 (38-53) years old and smoked 25 (15-40) pack-years; 55% had plaque. Pack-years, age, male sex, nonwhite race, body mass index, systolic blood pressure, small low-density lipoproteins (LDLs), and total high-density lipoproteins were independently associated with CIMT (model R(2) =0.434, P<.001). Pack-years (odds ratio [OR], 1.14 per 10 pack-years; P=.001), age (OR, 1.75 per 10 years; P<.001), body mass index (OR, 0.91 per 5 kg/m(2) ; P=.035), and small LDLs (OR, 1.11 per 100 nmol/L; P<.001) were independently associated with carotid plaque presence (model χ(2) =210.7, P<.001). The association between pack-years and carotid plaque was stronger in women (OR, 1.09 per 10 pack-years, P(interaction) =.018).

Download full-text


Available from: Megan E Piper, Oct 06, 2015
16 Reads
  • Source
    • "Moreover, in clinical cardiology, smokers often present (at a younger age) myocardial infarction without extensive visible coronary atherosclerosis [2,15]. Although epidemiological studies have consistently shown that cigarette smoking is associated with higher CIMT [16,17], the mechanisms are likely multifaceted and not yet fully understood. It has been previously suggested that cigarette smoking has a specific fibrogenic effect which causes intimal thickening [3,4]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although cigarette smoking has been associated with carotid intima-media thickness (CIMT) the mechanisms are yet not completely known. Lysophosphatidylcholine (lysoPC), a main product of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, appears to be a major determinant of the pro-atherogenic properties of oxidized LDL (oxLDL) and to induce proteoglycan synthesis, a main player in intimal thickening. In this study we assessed whether cigarette smoking-induced oxidative stress may influence plasma Lp-PLA2 and lysoPC and Lp-PLA2 expression in peripheral blood mononuclear cells (PBMC), as well as the relationship between lysoPC and CIMT. 45 healthy smokers and 45 age and sex-matched subjects participated in this study. Smokers, compared to non-smokers, showed increased plasma concentrations of oxLDL, Lp-PLA2 and lysoPC together with up-regulation of Lp-PLA2 (mRNA and protein) expression in PBMC (P<0.001). Plasma Lp-PLA2 positively correlated with both lysoPC (r=0.639, P<0.001) and PBMC mRNA Lp-PLA2 (r=0.484, P<0.001) in all subjects. Moreover CIMT that was higher in smokers (P<0.001), positively correlated with lysoPC (r=0.55, P<0.001). Then in in vitro study we demonstrated that both oxLDL (at concentrations similar to those found in smoker's serum) and oxidized phospholipids contained in oxLDL, were able to up-regulate mRNA Lp-PLA2 in PBMC. This effect was likely due, at least in part, to the enrichment in oxidized phospholipids found in PBMC after exposure to oxLDL. Our results also showed that in human aortic smooth muscle cells lysoPC, at concentrations similar to those found in smokers, increased the expression of biglycan and versican, two main proteoglycans. In smokers a further effect of raised oxidative stress is the up-regulation of Lp-PLA2 expression in PBMC with subsequent increase of plasma Lp-PLA2 and lysoPC. Moreover the correlation between lysoPC and CIMT together with the finding that lysoPC up-regulates proteoglycan synthesis suggests that lysoPC may be a link between smoking and intimal thickening.
    PLoS ONE 12/2013; 8(12):e83092. DOI:10.1371/journal.pone.0083092 · 3.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tumor embolism occurs in 30 to 50% of all cases of cardiac myxoma, but the causes are still uncertain. Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the extracellular matrix (ECM) and play a crucial role in plaque instability and aortic aneurysm development, in addition to cancer and heart failure. To determine whether MMP activity contributes to tumor embolism, we examined 27 left atrium-sided myxomas, 10 of which showed clinical signs of peripheral embolism. Immunohistochemistry (in all cases) and Western blotting, and in situ and in-gel zymography (in four embolic and six nonembolic consecutive tumors) demonstrated higher expression and activity of MT1-MMP, pro-MMP-2, and pro-MMP-9 in embolic myxomas, whereas pro-MMP-1, MMP-3, and TIMP-1 levels were similar to those of nonembolic tumors. Reverse transcriptase-polymerase chain reaction demonstrated that increased MMP activity was due, at least in part, to increased transcription and that TIMP-2 transcripts increased in embolic myxomas. In vitro, embolic tumor cells retained higher MT1-MMP and pro-MMP-2 levels in basal conditions and after stimulation with interleukin-1beta and interleukin-6. Increased MMP synthesis and release correlated with enhanced ECM degradation products containing glycosaminoglycan chains in embolic myxoma tissue. Our results strongly suggest that MMP overexpression may contribute to an excessive degradation of tumor ECM and increase the risk of embolism in cardiac myxomas.
    American Journal Of Pathology 07/2005; 166(6):1619-28. DOI:10.1016/S0002-9440(10)62472-8 · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: the effects of smoking and smoking cessation on lipoproteins have not been studied in a large contemporary group of smokers. This study was designed to determine the effects of smoking cessation on lipoproteins. this was a 1-year, prospective, double-blind, randomized, placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies. Fasting nuclear magnetic resonance spectroscopy lipoprotein profiles were obtained before and 1 year after the target smoking cessation date. The effects of smoking cessation and predictors of changes in lipoproteins after 1 year were identified by multivariable regression. the 1,504 current smokers were (mean [SD]) 45.4 (11.3) years old and smoked 21.4 (8.9) cigarettes per day at baseline. Of the 923 adult smokers who returned at 1 year, 334 (36.2%) had quit smoking. Despite gaining more weight (4.6 kg [5.7] vs 0.7 kg [5.1], P < .001], abstainers had increases in high-density lipoprotein cholesterol (HDL-C) (2.4 [8.3] vs 0.1 [8.8] mg/dL, P < .001), total HDL (1.0 [4.6] vs -0.3 micromol/L [5.0], P < .001), and large HDL (0.6 [2.2] vs 0.1 [2.1] micromol/L, P = .003) particles compared with continuing smokers. Significant changes in low-density lipoprotein (LDL) cholesterol and particles were not observed. After adjustment, abstinence from smoking (P < .001) was independently associated with increases in HDL-C and total HDL particles. These effects were stronger in women. despite weight gain, smoking cessation improved HDL-C, total HDL, and large HDL particles, especially in women. Smoking cessation did not affect LDL or LDL size. Increases in HDL may mediate part of the reduced cardiovascular disease risk observed after smoking cessation.
    American heart journal 01/2011; 161(1):145-51. DOI:10.1016/j.ahj.2010.09.023 · 4.46 Impact Factor
Show more