Impact of a Partial Smoke-Free Legislation on Myocardial Infarction Incidence, Mortality and Case-Fatality in a Population-Based Registry: The REGICOR Study

<div><h3>Background and Objective</h3><p>Coronary heart disease (CHD) is the leading cause of death, and smoking its strongest modifiable risk factor. Our aim was to determine the impact of the Spanish 2006 partial smoke-free legislation on acute myocardial infarction (AMI) incidence, hospitalization and mortality rates, and 28-day case-fatality in Girona, Spain.</p> <h3>Methods</h3><p>Using a population-based registry (the REGICOR Study), we compared population incidence, hospitalization, and mortality rates, and 28-day case-fatality in the pre- and post-ban periods (2002–2005 and 2006–2008, respectively) by binomial regression analysis adjusted for confounding factors. We also analyzed the ban's impact on the outcomes of interest using the AMI definitions of the American Heart Association (AHA)/European Society of Cardiology (ESC) and the World Health Organization (WHO)-Monitoring trends and determinants in cardiovascular diseases (MONICA).</p> <h3>Results</h3><p>In the post-ban period, AMI incidence and mortality rates significantly decreased (relative risk [RR] = 0.89; 95% confidence interval [CI] = 0.81–0.97 and RR = 0.82; 95% CI = 0.71–0.94, respectively). Incidence and mortality rates decreased in both sexes, especially in women, and in people aged 65–74 years. Former and non-smokers (passive smokers) showed diminished incidence rates. Implementation of the ban was not associated with AMI case-fatality. Models tended to be more significant with the WHO-MONICA than with the AHA/ESC definition.</p> <h3>Conclusions</h3><p>The 2006 Spanish partial smoke-free legislation was associated with a decrease in population AMI incidence and mortality, particularly in women, in people aged 65–74 years, and in passive smokers. These results clarify the association between AMI mortality and the enactment of a partial smoke-free legislation and reinforce the effectiveness of smoking regulations in preventing CHD.</p> </div

Annual AMI incidence, hospitalization and mortality rates and 28-day case-fatality by age group or sex, in 2002–2008, according to the AHA/ESC AMI definition.

<p><i>AMI</i> acute myocardial infarction, <i>AHA</i> American Heart Association, <i>ESC</i> European Society of Cardiology.</p

Characteristics of patients with AMI in Girona Province (Spain), in 2002–2008, according to the AHA/ESC AMI definition.

<p><i>AMI</i> acute myocardial infarction, <i>AHA</i> American Heart Association, <i>ESC</i> European Society of Cardiology, <i>SD</i> Standard deviation.</p

RR and 95% CI for AMI mortality and 28-day case-fatality comparing the period after to the period before the 2006 partial smoke-free legislation enactment, according to the AHA/ESC AMI definition.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053722#s3" target="_blank">Results</a> from negative binomial regression analysis.</p>*<p>p-value<0.05.</p><p><i>RR</i> relative risk, <i>CI</i> confidence interval, <i>AMI</i> acute myocardial infarction, <i>AHA</i> American Heart Association, <i>ESC</i> European Society of Cardiology.</p

Annual AMI incidence and mortality crude rates by sex and age group.

<p>Time trend of the 2002–2008 AMI incidence and mortality crude rates according to the AHA/ESC AMI definition. Annual rates are plotted in the middle of each year. A vertical bar in 2006 indicates the start of the partial smoke-free legislation. Upper left panel: AMI incidence in women, upper right panel: AMI mortality in women, lower left panel: AMI incidence in men, lower right panel: AMI mortality in men. Abbreviations: <i>AMI</i> acute myocardial infarction, <i>AHA</i> American Heart Association, <i>ESC</i> European Society of Cardiology.</p

Baseline Characteristics of cases in the British Heart Foundation-Family Heart Study and the Myocardial Infarction Genetics studies.

<p>Data are means and standard deviations or counts and percentages, BHF-FHS: British Heart Foundation Family Heart Study; MIGen: Myocardial Infarction Genetics Consortium; MI: myocardial infarction; BMI: body mass index.</p><p>Baseline Characteristics of cases in the British Heart Foundation-Family Heart Study and the Myocardial Infarction Genetics studies.</p

Identification of a new locus and validation of previously reported loci showing differential methylation associated with smoking. The REGICOR study

<p>Smoking increases the risk of many diseases and could act through changes in DNA methylation patterns. The aims of this study were to determine the association between smoking and DNA methylation throughout the genome at cytosine-phosphate-guanine (CpG) site level and genomic regions. A discovery cross-sectional epigenome-wide association study nested in the follow-up of the REGICOR cohort was designed and included 645 individuals. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Smoking status was self-reported using a standardized questionnaire. We identified 66 differentially methylated CpG sites associated with smoking, located in 38 genes. In most of these CpG sites, we observed a trend among those quitting smoking to recover methylation levels typical of never smokers. A CpG site located in a novel smoking-associated gene (cg06394460 in <i>LNX2</i>) was hypomethylated in current smokers. Moreover, we validated two previously reported CpG sites (cg05886626 in <i>THBS1</i>, and cg24838345 in <i>MTSS1</i>) for their potential relation to atherosclerosis and cancer diseases, using several different approaches: CpG site methylation, gene expression, and plasma protein level determinations. Smoking was also associated with higher <i>THBS1</i> gene expression but with lower levels of thrombospondin-1 in plasma. Finally, we identified differential methylation regions in 13 genes and in four non-coding RNAs. In summary, this study replicated previous findings and identified and validated a new CpG site located in <i>LNX2</i> associated with smoking.</p

A schematic illustration of SNP selection process for the primary analysis.

<p>A schematic illustration of SNP selection process for the primary analysis.</p

SNP selection process for the secondary analysis.

<p>SNP selection process for the secondary analysis.</p

Suggestive SNP-SNP interactions—primary analysis.

<p>SNP: single nucleotide polymorphism, Chr: chromosome; MAF: minor allele frequency; BHF-FHS: British Heart Foundation Family Heart Study; MIGen: Myocardial Infarction Genetics Consortium; SNPA Pvalue: level of nominal statistical significance for single marker association with coronary artery disease for SNP A; SNPB Pvalue: level of nominal statistical significance for single marker association with coronary artery disease for SNP B; Int. Pvalue BHF-FHS: interaction P value in BHF-FHS; Int. Pvalue MIGen: interaction P value in MIGen; N/A: replication not available. PDE11A: phosphodiesterase 11A; SEC1P: secretory blood group 1, pseudogene; SERPINA12: serpin peptidase inhibitor, clade A; SRI: sorcin; ZHX2: zinc fingers and homeoboxes 2; NR5A2: nuclear receptor subfamily 5, group A, member 2; ANGPTL4: angiopoietin-like 4; NRG3: neuregulin 3; RPSAP15: ribosomal protein SA pseudogene 15; CSRP3: cysteine and glycine-rich protein 3; GSTM3: glutathione S-transferase mu 3; RYR2: ryanodine receptor 2; TBXAS1: thromboxane A synthase 1; TAC1: tachykinin, precursor 1; P2RX4: purinergic receptor P2X, ligand-gated ion channel, 4; SCARB2: scavenger receptor class B, member 2; NOD1: nucleotide-binding oligomerization domain containing 1; PDGFD: platelet derived growth factor D.</p><p>Suggestive SNP-SNP interactions—primary analysis.</p