Particulate matter and atherosclerosis: a bibliometric analysis of original research articles published in 1973–2014

Background Epidemiological and experimental studies have suggested that exposure to particulate air pollution may promote progression of atherosclerosis. Methods In the present study, the characteristics and trends of the research field of particulate matter (PM) and atherosclerosis were analyzed using bibliometric indicators. Bibliometric analysis was based on original papers obtained from PubMed/MEDLINE search results (from 1973 to 2014) using Medical Subject Headings (MeSH) terms. A fully-detailed search strategy was employed, and articles were imported into the Thomson Data Analyzer (TDA) software. Results The visualizing network of the collaborative researchers was analyzed by Ucinet 6 software. Main research topics and future focuses were explored by co-word and cluster analysis. The characteristics of these research articles were summarized. The number of published articles has increased from five for the period 1973–1978 to 89 for the period 2009–2014. Tobacco smoke pollution, smoke and air PM were the most studied targets in this research field. Coronary disease was the top health outcome posed by PM exposure. The aorta and endothelium vascular were the principal locations of atherosclerotic lesions, which were enhanced by PM exposure. Oxidative stress and inflammation were of special concern in the current mechanistic research system. The top high-frequency MeSH terms were clustered, and four popular topics were further presented. Conclusion Based on the quantitative analysis of bibliographic information and MeSH terms, we were able to define the study characteristics and popular topics in the field of PM and atherosclerosis. Our analysis would provide a comprehensive background reference for researchers in this field of study.


Background
Exposure to air particulate matter (PM) may result in various diseases including cardiovascular diseases (CVD) such as atherosclerosis, myocardial infarction, stroke, myocardial ischemia, coronary diseases and cardiac arrhythmia. Its etiology and pathogenic mechanisms may be complex, which include pulmonary and systemic inflammation, accelerated atherosclerosis and altered cardiac autonomic functions [1,2]. PM contributes to increased cardiac risk by initiating and promoting atherosclerotic progression, which is the underlying cause of most cardiovascular diseases [3]. There is ample epidemiological, clinical and experimental evidence supporting the association of PM with atherogenesis [4][5][6][7]. Related research on PM exposure-enhanced atherosclerosis has attracted greater attention and is becoming an important, rapid-progressing field in the coming years. Therefore, it is necessary to survey bibliometric characteristics and portray the overall trend of these research fields.
Bibliometrics refers to a research methodology employed in library and information sciences, which utilizes quantitative analysis and statistics to describe the bibliographic information of articles (year publication, title, authors, publisher, affiliations, etc.) within a given topic, field, institution, and/or country [1,8]. Recently, bibliometrics has been used to explore trends in biomedical, medical and environmental research fields; such as the mapping of global drinking water from 1992 to 2011 [8], air PM on the cardiovascular system [1], urban health for the period 1978-2012 [1], stem cell research in Iran [9], cardiovascular research from Latin America from 1999 to 2008 [10], and ophthalmology research from 1997 to 2009 [11]. Bibliometrics applies quantitative and statistical methods to analyze a variety of phenomena across scientific literatures. Literature data are mainly derived from international literature databases such as PubMed/ MEDLINE [1], Springerlink [12], and Web of Science [13]. In the present study, we attempted to analyze the characteristics and trends within the research fields of PM and atherosclerosis using the bibliometric approach by conducting a search on the PubMed/MEDLINE database using Medical Subject Headings (MeSH) terms.

Data sources
The database used in the present study was PubMed/MED-LINE, which is provided by the National Library of Medicine (NLM) in America. The NLM covers the largest number of publications on life sciences and biomedical research.

Search strategy
MeSH, compiled by NLM for its bibliographies and cataloging [14], were used to perform the literature search and exploration of popular topics in these research fields. As illustrated in Table 1, these MeSH terms (2015 MeSH) were combined using the Boolean operator AND. The first group of MeSH terms included PM and the expanded versions of the MeSH term such as particle size, air pollution and air pollutants. The second group of MeSH terms included atherosclerosis and the expanded versions of the MeSH of arteriosclerosis, atherosclerotic plaque, carotid artery diseases and coronary diseases.

Data collection
Data was obtained through a comprehensive literature search of the PubMed/MEDLINE database on the 8th of January, 2015. The eligible records of 259 articles were downloaded. Bibliographic information included the title, abstract, name of authors, journal title, year of publication, and the corresponding authors' address.

Data analysis
These records were imported into the Thomson Data Analyzer software version 3.0 (TDA; Thomson Reuters Co., New York, NY, USA), which could provide a global view of the technology area. In order to analyze characteristics and trends, the data analysis process consisted of five parts: data cleaning, bibliographic information analysis, MeSH terms analysis, co-occurrence of word (co-word) analysis, and cluster analysis. In order to ensure the accuracy of these results, reduplicates and conflicting data were cleaned using the TDA software, which offers an efficient and accurate automatic data cleansing tool. For subsequent analysis, a bibliographic information database with 259 articles and 683 MeSH terms used during the period 1973-2014 was established. TDA was used to process and analyze bibliographic information (year of publication, journal title, affiliation, author and country).
The visualized network of the collaborative researchers was analyzed by Ucinet 6 (Analytic Technologies Co., Lexington, KY, USA) software, which is considered the most popular social network analysis software and features a strong matrix analysis function. The 50 × 50 cooccurrence frequency matrix of the 50 most published authors was calculated to reflect the collaborative relationship between top researchers. The betweenness centrality for measures of structural centrality in social networks can reflect the degree of centralization of the research network [15]. MeSH terms were ranked according to frequency. The top 225 MeSH terms (with a cumulative frequency of 74.2 %) were defined as high-frequency terms for the subsequent research trend analysis.
Co-occurrence of word (co-word) analysis is a basic and important approach for themes exploration, which include three steps: measurement of the links between terms, organization of clusters, and concluding the topics [1]. The 225 × 225 co-occurrence frequency matrices of the top 225 MeSH terms were conducted using the TDA software. After conducting the cluster analysis with SPSS software version 17.0 (Chicago, IL, USA), the MeSH terms were combined to create 12 clusters according to the degree of similarity. Based on the cluster analysis of high-frequency MeSH terms, popular topics in the research fields of PM and atherosclerosis were concluded.

Characteristics of publications Publication outputs
Due to the large number of publications retrieved, more attention was given to the research area of PM and   bridge that connected the whole network (betweenness centrality = 31).

Characteristics of the high-frequency MeSH terms
As shown in Tables 2 and 3, the MeSH terms were ranked according to frequency and were classified into eight categories including PM, objects-human, objects-animals, objects-lesions, main outcomes, mechanisms, main methods and factors. Epidemiological studies, in which 'middle-aged' and 'aged' populations were the main focus, comprised of a significant proportion of the research field of PM exposure-related atherosclerosis; and were mostly cohort studies. Mice, gene knockout mice and disease model animals were the most frequently chosen subjects in vivo. Oxidative stress and inflammation were the most popular mechanisms hypothesized. The methods of cell culture in vitro were very important in toxicological and mechanistic studies, and endothelial cells were the major experimental model. Tobacco smoke pollution, smoke and air PM were the most studied targets in the research fields. The aorta and endothelium vascular were the principal atherosclerosis lesion locations, which were enhanced by PM exposure. Coronary disease was the top health outcome posed by PM exposure. Time, gender and diet were the top three risk factors that may influence the degree of atherosclerosis accelerated by PM exposure.

Research tendencies and hotspots
Cluster analysis of the top 225 high-frequency MeSH terms was classified into 10 clusters, which explained 99.05 % of total variations. According to the roles of MeSH terms in the studies and relying on professional judgment, the terms in every cluster were categorized into objects, exposure variables, main outcome variables, factors, lesions, designs/methods and contents/mechanisms. Cluster analysis can group separate data types into clusters, and help identify valuable clues of possible research issues. After the synthetic analysis of the ten clusters, four research hotspots related to PM and atherosclerosis were identified, which provide a reference for further research in these fields (Tables 4, 5, 6 and 7). Results of the cluster analyses reflected the research tendencies in these research fields. Topic 1 was formed by combining Clusters 1, 3, and 9; Cluster 2 was combined with Cluster 4 to form Topic 2; Clusters 5, 7, and 8 were converged to form Topic 3; and Cluster 6 was combined with Cluster 10 to form Topic 4 (Table 8).

Discussion
Topic 1 (Clusters 1, 3, and 9) included epidemiological studies on the associations between tobacco exposure and atherosclerosis. It is well-known that smoking is an important source of indoor air PM pollution [16] and  levels of PM 2.5 is a marker for secondhand tobacco smoke (SHS) [17]. Both active smoking and exposure to environmental tobacco smoke (ETS) were associated with the progression of atherosclerosis [18,19]. Cigarette smoking is a powerful risk factor for atherosclerotic diseases in middle-aged and aged populations [20][21][22]. Moreover, smoking is associated with lipoprotein abnormalities, which promote arterial lipid accumulation and atherogenesis [23][24][25][26]. SHS exposure or the inhalation of ETS is an independent risk factor for subclinical coronary atherosclerosis, coronary heart disease (CHD) and peripheral arterial disease (PAD). In addition, longterm exposure to SHS creates an imbalance in the lipid profile. This imbalance leads to lipid accumulation in the blood vessels of the heart and aorta in experimental     [27]. In this topic, the association between familial and fetal tobacco smoke exposures and vascular damage also received close attention, because young adults/children/infants are at high risk of SHS exposure (Cluster 9). These studies show that thicker common carotid artery intima-media thickness (CIMT) in young adulthood is associated with fetal tobacco smoke exposure [28][29][30]. Exposure to ETS is independently associated with decreased brachial artery flow-mediated dilation, decreased aortic elastic properties and increased ApoB levels among adolescents with increased cotinine level (a sensitive and specific biomarker of ETS exposure) [29,31,32]. Moreover, smokefree legislation is associated with lower risk of smokingrelated cardiac and cerebrovascular diseases [33][34][35]. Topic 2 (Clusters 2 and 4) covered epidemiological studies on the associations between environmental PM exposures and atherosclerosis. Epidemiological findings show a clear association between long-term exposure to PM 2.5 /PM 10 and atherosclerosis. The studies reviewed on this topic focused on the effects of PM air pollution on subclinical atherosclerosis by means of noninvasive imaging (a predictor of cardiovascular events). Longterm PM concentrations are associated with increased CIMT progression [36][37][38][39], but does not appear to be associated with greater arterial stiffness [40]. CIMT, a marker of subclinical atherosclerosis, is associated with atherosclerosis development and progression in middleaged populations [41]. The investigation of links between PM exposures and subclinical atherosclerosis mostly adopts the cohort and cross-sectional studies. The most studied cohort is the Multi-Ethnic Study of Atherosclerosis (MESA) conducted across six study sites in the USA [36,38,40,42]. In addition, exposure to traffic is also associated with atherosclerosis [43].
Topic 3 (Clusters 6 and 10) included studies on the different roles of PM components/sources in health effects. On this topic, the source that has the most concern is vehicle emissions (Cluster 10), which is linked with heart rate variability (HRV) [44], cardiac repolarization [45] and endothelial gene regulation [46]. The sources of PM from fire/combustion emission are also issues of concern. Exposure to ultrafine particles during fire suppression is considered a potential contributing factor for CHD [47].
Combustion emissions cause pro-atherosclerotic responses in ApoE −/− mice [48]. Moreover, these components (carbon black, metals, etc.) deserve closer attention. Nano-sized carbon black particles are associated with modest vasomotor impairment [49]. The zinc metal component of PM drives cardiovascular health effects, as well as the possible susceptibility induced by hyperlipidemia [50]. In addition, other air pollutants (nitrogen dioxide, sulfur dioxide, carbon monoxide, etc.) may also induce cardiovascular risk on their own, or combined with PM exposure. Elevated concentrations of PM and nitrogen dioxide increase the risk of supraventricular runs, as well as the number of ventricular runs [51].
Topic 4 (Clusters 5, 7, and 8) included toxicological studies on PM-induced arteriosclerosis. Mice, miceknockout and disease model animals were chosen as study subjects for animal experiments (Cluster 8). ApoE −/− mice, which is probably of more concern, lacks apolipoprotein E, a high-affinity ligand for lipoprotein receptors, and develops atherosclerotic plaques in a fashion similar to humans [52]. In ApoE −/− mice, exposure to both ambient PM and tobacco smoke increased the plaque area in the pathological analysis of the aorta [6,[53][54][55][56]. Vascular endothelial cells were chosen as study subjects to explore molecular biology mechanisms (Cluster 5). On this topic, the induction of oxidative stress [57,58] and mitochondrial DNA (mtDNA) damage [53,59,60] play a key role in the progression of atherosclerosis (Cluster 7).

Conclusions
Increasing attention has been given to the research field of PM and atherosclerosis. The number of published articles has increased from five for the period 1973-1978 to 89 for the period 2009-2014. The characteristics of the research literature in the fields of PM and atherosclerosis can be obtained through the quantitative analysis of bibliographic information and MeSH terms. Bibliographic information includes annual publications, authors, journals, institutions and countries; which can support a deeper understanding of research directions in the future. Cluster analysis by MeSH terms can provide clues that suggest popular topics in these fields, and help determine research emphases and priorities. Based on the quantitative analysis of bibliographic information and MeSH terms, we found that "tobacco smoke pollution" and "smoke and air particulate matter" were the most studied targets in the research field of PM and atherosclerosis.
It should be pointed out that the overall characteristics of these studies might be affected to a certain extent by the interest and funding of the researchers. In conclusion, the bibliometric analysis method is an effective approach for providing the characterization of a given research field, and can be adopted by other research fields as well.