Genetic Loci Associated With C-Reactive Protein Levels and Risk of Coronary Heart Disease

Elliott, Paul; Chambers, John C.; Zhang, Weihua; Clarke, Robert; Hopewell, Jemma C.; Peden, John F.; Erdmann, Jeanette; Braund, Peter S.; Engert, James C.; Bennett, Derrick; Coin, Lachlan; Ashby, Deborah; Tzoulaki, Ioanna; Brown, Ian J.; Mt‐Isa, Shahrul; McCarthy, Mark I.; Peltonen, Leena; Freimer, Nelson B.; Farrall, Martin; Ruokonen, Aimo; Hamsten, Anders; Lim, Noha; Froguel, Philippe; Waterworth, Dawn; Vollenweider, Péter; Waeber, Gérard; Järvelin, Marjo‐Riitta; Mooser, Vincent; Scott, James G.; Hall, Alistair S.; Schunkert, Heribert; Anand, Sonia S.; Collins, Rory; Samani, Nilesh J.; Watkins, Hugh; Kooner, Jaspal S.

doi:10.1001/jama.2009.954

Cited by 571 publications

(444 citation statements)

References 73 publications

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“…Recent epidemiological work has failed to find associations between functional genetic variants associated with elevated CRP levels and coronary heart disease. 69 Furthermore, adjustment for other metabolic factors attenuated this association, which is in agreement with another study, 70 suggesting that either these factors may mediate the association or they both share a common antecedent.…”

Section: Potential Risk Factors For Amdsupporting

confidence: 88%

The prevalence and analysis of risk factors for age-related macular degeneration: 18-year follow-up data from the Speedwell eye study, United Kingdom

Ngai

Stocks

Sparrow

et al. 2011

Eye

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Aims/Purpose To determine the prevalence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in men aged 65-83 years living in the Speedwell region of Bristol, United Kingdom and identify modifiable risk factors. Methods A total of 2348 men recruited to the Speedwell prospective cohort study in 1979 were followed up in 1997 with an eye questionnaire and had retinal photographs that were assessed using the International Classification System for ARM. Results In all, 934 men (66.8% response rate) attended with a mean of 17.9 years (15.3-20.6 years) follow-up. Early ARM (grades 2-3) was found in 9.2% (95% confidence interval (CI) 7.4%, 11.4%) and late age-related maculopathy (grade 4, AMD) in 0.5% (95% CI 0.2%, 1.2%). The risk of ARM (grades 2-4) was increased with raised C-reactive protein and consumption of lard and solid fats, whereas triglyceride levels were associated with a lower risk. The latter were confirmed in multivariable analyses and in addition, haemodynamic measures also predicted risk (eg mean arterial pressure odds ratio (OR) per z-score 1.37, 95% CI 1.04, 1.79). Conclusions In a representative cohort of men aged 65-83 from Bristol, United Kingdom, many had macular changes that put them at higher risk of developing AMD. Various modifiable exposures were associated with an increased risk ARM/AMD. Opportunities for screening and undertaking secondary prevention interventions need to be explored to prevent progression of the disease and blindness.

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Section: Potential Risk Factors For Amdsupporting

confidence: 88%

The prevalence and analysis of risk factors for age-related macular degeneration: 18-year follow-up data from the Speedwell eye study, United Kingdom

Ngai

Stocks

Sparrow

et al. 2011

Eye

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“…8,39,40 Whether CRP also has a causal relationship to cardiovascular diseases, is under debate. 8,41,42 In contrast to CRP, SAA is more often discussed as causal factor for cardiovascular disease. 15,16,43 Furthermore, SAA exhibits pro-inflammatory characteristics such as the attraction of phagocytes, the induction of proinflammatory cytokines and the delay of neutrophil apoptosis, 11,12 which may contribute to the pathogenesis of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes

Baumann

Gube

Markert

et al. 2017

J Expo Sci Environ Epidemiol

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Zinc-and copper-containing welding fumes increase systemic C-reactive protein (CRP). The aim of this study was to investigate the performance of the biomarkers serum amyloid A (SAA) and soluble vascular cell adhesion molecule-1 (VCAM-1) in this regard. Fifteen male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc for 6 h. Plasma samples were collected before, 6 and 24 h after start of exposure and biomarkers therein were measured by electrochemiluminescent assay. For each exposure, systemic concentrations of systemic SAA, but not VCAM-1, increased significantly at 24 h after exposure start compared with baseline ("copper only": P = 0.0005, "zinc only": P = 0.027, "copper and zinc": P = 0.001). SAA showed a wider range of concentrations than did CRP and its levels increased up to 19-fold after welding fume exposure. The recognition of copper as a potential harmful component in welding fumes, also independent from zinc, deserves further consideration. SAA might represent a new sensitive biomarker for potential subclinical sterile inflammation after inhalation of copper-and/or zinc-containing welding fumes. As elevations of CRP and SAA protein have both been linked to a higher risk for cardiovascular disease, these findings might particularly be important for long-term welders. Journal of Exposure Science and Environmental Epidemiology INTRODUCTIONA large number of workers are exposed to welding fumes containing various types of gases and metal particles in occupational settings. Depending on the constitution of the welding fumes and the respective exposure conditions, epidemiological studies have shown that welding fume exposure is associated with the risk of health impairment through respiratory illness, inflammation and cardiovascular disease. [1][2][3][4] Zinc and copper play an increasing role in modern joining technology, especially in the automotive industry, and hence exposures from workers become more frequent. In a recent study, a distinct increase of systemic C-reactive protein (CRP) has been shown after inhalation of welding fume from a metal inert gas brazing process of zinc-coated steel using a copper-containing welding wire at an average fume concentration of 2.5 mg/m 3 . 5 A further study tested the effect of elevated systemic CRP levels after exposure with three different doses of this welding fume and found increases of CRP after exposure with 2.0 and 2.5 mg/m 3 average fume concentration, but not at 1.4 mg/m 3 . Hence, it was concluded that the no-observed-effect level for systemic inflammation after such exposures was 1.4 mg/m 3 and the lowest observed effect level was 2.0 mg/m 3 . 6 This corresponds to zinc concentrations of 0.84 mg/m 3 and 1.2 mg/m 3 , respectively, and copper concentrations of 0.24 mg/m 3 and 0.34 mg/m 3 , respectively. 6 A subsequent third study showed that the observed effects were due to the zinc as well as copper present in the welding fume, as the welding fumes which contained either zinc and no cop...

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“…In line, a pathway analysis of the CARDIoGRAMplusC4D meta‐analysis has also shown a major role for variants in inflammatory genes (CARDIoGRAMplusC4D Consortium, 2013). By contrast, C‐reactive protein (CRP) appears to be rather a marker than a causal factor, as its genetic variation does not translate to CAD risk (Schunkert & Samani, 2008; Zacho et al , 2008; Elliott et al , 2009; C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC) (2011)).…”

Section: Inflammationmentioning

confidence: 99%

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

2016

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Cardiovascular diseases are leading causes for death worldwide. Genetic disposition jointly with traditional risk factors precipitates their manifestation. Whereas the implications of a positive family history for individual risk have been known for a long time, only in the past few years have genome‐wide association studies (GWAS) shed light on the underlying genetic variations. Here, we review these studies designed to increase our understanding of the pathophysiology of cardiovascular diseases, particularly coronary artery disease and myocardial infarction. We focus on the newly established pathways to exemplify the translation from the identification of risk‐related genetic variants to new preventive and therapeutic strategies for cardiovascular disease.

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Genetic Loci Associated With C-Reactive Protein Levels and Risk of Coronary Heart Disease

Cited by 571 publications

References 73 publications

The prevalence and analysis of risk factors for age-related macular degeneration: 18-year follow-up data from the Speedwell eye study, United Kingdom

The prevalence and analysis of risk factors for age-related macular degeneration: 18-year follow-up data from the Speedwell eye study, United Kingdom

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

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