Association of genetic variants rs7759938 (upper panel) and rs314279 (lower panel) with adult metabolic profiles.

<p>All phenotypes were standardized prior to analyses. Two regression models were used: Model A including age as a covariate, and Model B including both the alternative SNP and age as covariates. Subjects using lipid lowering drugs or with lipid levels +/−5 standard deviations (SD) from the mean were excluded from the lipid/lipoprotein analysis. Only subjects with normal glucose tolerance not receiving treatment for diabetes were included in the regression analyses of glucose and serum insulin. The effect allele for both rs7759938 and rs314279 is C. ApoA1 =  Apolipoprotein A1, ApoB  =  Apolipoprotein B, FP  =  Fasting plasma. FS  =  Fasting serum, 2H glucose  =  Plasma glucose concentrations at 2 h after a 75 g oral glucose load. Participants of the oral glucose test were instructed to fast for 10 hours. ^# The variable was logarithm-transformed prior to the analysis.</p

Kaplan-Meier Curves According to Troponin Categories as Measured by Contemporary-Sensitivity, High-Sensitivity and Super-Sensitivity Assays for MACE and HF after Adjustment for Age and Gender.

<p>Dotted lines indicate the 95% confidence intervals. MACE = major adverse cardiac events, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = highly sensitive troponin I measured by high-sensitivity assay, ss-cTnI = troponin I measured by super-sensitivity assay. Please see the footnote to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090063#pone-0090063-t002" target="_blank">Table 2</a> for the cut points of the troponin categories.</p

Net Reclassification Improvement (NRI) and Clinical NRI for Various Endpoints for Baseline Troponin Assessed by Contemporary-Sensitivity, High-Sensitivity and Super-Sensitivity Assays in Addition to the Standard Framingham Risk Score.

<p>NRI = net reclassification improvement, clinical NRI = NRI for individuals with an intermediate 10-year risk (5–20%) according to the Framingham Risk Score, MACE = major adverse cardiac events, CVD = cardiovascular disease, MI = myocardial infarction, HF = heart failure, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = troponin I measured by high-sensitivity assay, ss-cTnI = troponin I measured by super-sensitivity assay, ns = not significant.</p

Absolute and Relative Distributions of Troponin I Concentrations in the Study Population.

<p>The categories were defined as follows. For the contemporary-sensitivity assay, troponin category 1 is 0–1 pg/mL (lowest observed non-zero value), category 2 is 1–10 pg/mL (LOD), and category 3 is >10 pg/mL. For the high-sensitivity assay, troponin category 1 is 0–1.9 pg/mL (LOD), category 2 1.9–5.1 pg/mL (same percentile as 10 pg/mL for contemporary troponin), and category 3 is >5.1 pg/mL. For the super-sensitivity assay, troponin category 1 is 0–1.0 pg/mL (median limit of detection), category 2 1.0–5.1 pg/mL (according to the percentiles of contemporary troponin), and category 3 is >5.1 mg/mL.</p><p>cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = troponin I measured by high-sensitivity assay, ss-cTnI = troponin I measured by super-sensitivity assay, LOD = limit of detection.</p

Baseline Characteristics of the Study Population by Gender.

<p>Persons with prevalent MACE and pregnant women have been excluded. Binary variables are shown in absolute counts and percentages. For continuous variables the median and the IQR are shown.</p><p>MI = Myocardial infarction, MACE = major adverse cardiac events, BP = blood pressure, HDL = high-density-lipoprotein, CRP = c-reactive protein, NT-proBNP = N-terminal pro-brain natriuretic peptide, IQR = interquartile range, CVD = cardiovascular disease, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = troponin I measured by high-sensitivity assay, ss-cTnI = troponin measured by super-sensitivity assay</p

Hazard Ratios from Cox Regression Models for Baseline Troponin Assessed by Contemporary-Sensitivity, High-Sensitivity and Super-Sensitivity Assays for Various Endpoints after Adjustment for the Framingham Risk Score.

<p>Shown are the hazard ratios for continuous troponin concentration per 1-SD increment and for categorical troponin concentration, comparing the highest with the lowest defined category. Please see the footnote to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090063#pone-0090063-t002" target="_blank">Table 2</a> for cut points of the categories.</p><p>Abbreviations: MACE = major adverse cardiac events, CVD = cardiovascular disease, MI = myocardial infarction, HF = heart failure, HR = hazard ratio, CI = confidence interval, cs-cTnI = troponin I measured by contemporary-sensitivity assay, hs-cTnI = highly sensitive troponin, ss-cTnI = supersensitive troponin, ns = not significant.</p

Clinical characteristics of the study samples.

<p>HSDS  =  The Helsinki Sudden Death Study, SCD  =  sudden cardiac death, SD  =  standard deviation, TASTY  =  The Tampere Autopsy Study.</p>*<p>Helsinki/Vantaa, Turku/Loimaa, North Karelia, and North Savo.</p>†<p>Helsinki/Vantaa, Turku/Loimaa, North Karelia, North Savo, and Oulu province.</p>‡<p>Helsinki/Vantaa, Turku/Loimaa, North Karelia, North Savo, Oulu province, and Lapland.</p

Forest plot of SCD risk ratios for rs41312391 and rs2200733.

<p>The figure shows point estimates for relative SCD risk (squares, area proportional to the inverse-variance weight) and 95% confidence intervals (horizontal lines) in all six cohorts, adjusting for sex and geographic region. The lateral tips of the diamonds indicate the 95% confidence intervals for the relative risk and the widest point of the diamond the relative risk estimate in the meta-analysis. HSDS  =  The Helsinki Sudden Death Study, SCD  =  sudden cardiac death, TASTY  =  The Tampere Autopsy Study.</p

Cardiovascular risk factors associated with SCD in a multivariate model in four population-based cohorts.

<p>BMI  =  body mass index, BP  =  blood pressure, CHD  =  coronary heart disease, CI  =  confidence interval, HDL  =  high-density lipoprotein cholesterol, HR  =  hazard ratio (in Cox regression), I²  =  measure of heterogeneity between studies, SCD  =  sudden cardiac death, TC  =  total cholesterol.</p>*<p>Random-effects meta-analysis was used because of significant heterogeneity between studies.</p>†<p>Leisure-time physical activity (moderate/high vs. low).</p