Prospective Studies of the Association of Serum Uric Acid and CHD, Grouped by Various Characteristics

<p>Conventions are the same as in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020076#pmed-0020076-g001" target="_blank">Figure 1</a>. *, each sex-specific estimate was treated as a “study”; †, two studies (6 and 13) were drawn from general practice registers; §, risk factors adjusted for included: smoking, blood pressure, total cholesterol, triglycerides, alcohol consumption, obesity, use of cardiovascular medication, history of hypertension, and history of diabetes. PTA, phosphotungstic acid.</p

Meta-Analysis of Prospective Observational Studies of Serum Uric Acid and CHD in Essentially General Populations, Subdivided by Sex

<p>Conventions are the same as in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020076#pmed-0020076-g001" target="_blank">Figure 1</a>. Combined odds ratios and their CIs are indicated by unshaded diamonds for subtotals and shaded diamonds for grand totals. +, adjustment reported only for age and sex; ++, adjustment for these plus smoking; +++, adjustment for these plus some additional established risk factors; ++++, adjustment for these plus existing cardiovascular disease. Study abbreviations: ARIC, Atherosclerosis Risk in Communities; BIRNH, Belgium Interuniversity Research on Nutrition and Health; BRHS, British Regional Heart Study; CHA, Chicago Heart Association Detection Project in Industry; GRIPS, Göttingen Risk Incidence and Prevalence Study; IIHDS, Israeli Ischemic Heart Disease Study; MONICA, World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease; NHANES, National Health and Nutrition Examination Survey; NHEFS, NHANES I Epidemiologic Follow-Up Study; PROCAM, Prospective Cardiovascular Munster Study.</p

Associations between Serum Uric Acid and CHD in 2,456 cases and 3,962 Controls in the Reykjavik Study at Different Levels of Established Risk Factors

<p>Squares indicate odds ratios, with the size of the square proportional to the effective sample size.</p

Baseline characteristics of coronary heart disease cases and matched controls in the Reykjavik Study, and correlations with t-PA antigen, D-dimer and VWF.

<p>Abbreviations: ESR, erythrocyte sedimentation rate; IQR, inter-quartile range.</p>*<p>Means (SDs) of log_e transformed values in cases and controls were 0.2 (0.5) and 0.0 (0.4) for triglycerides; 4.4 (1.6) and 4.0 (1.7) for lipoprotein (a); 0.8 (0.8) and 0.7 (0.8) for interleukin 6; 0.5 (1.1) and 0.2 (1.1) for C-reactive protein; 2.0 (1.0) and 1.9 (1.0) for erythrocyte sedimentation rate; 2.6 (0.5) and 2.5 (0.5) for t-PA antigen; 4.8 (1.0) and 4.8 (1.0) for D-dimer; and 4.7 (0.4) and 4.6 (0.4) for VWF.</p>†<p>Percentage differences and 95% CIs were calculated per 1 SD higher level or compared to the reference category of variables shown in the left column (adjusted for age, sex and period of recruitment).</p

Associations of baseline t-PA antigen, D-dimer and VWF with coronary heart disease risk (Reykjavik Study).

<p>Odds ratios (95% CI) for coronary heart disease are shown by fifths of baseline t-PA antigen, D-dimer and VWF, plotted against the geometric mean level in each category on a log-doubling scale. *Adjusted for age, sex, period of recruitment, smoking status, body mass index, systolic blood pressure, history of diabetes, total cholesterol and log_e triglycerides.</p

Characteristics of 21 published prospective studies of t-PA antigen, D-dimer and VWF.

<p><b>Abbreviations:</b><b>AmB</b>, American Bioproducts; <b>AmD</b>, American Diagnostica; <b>AP</b>, angina pectoris; <b>ARIC</b>, Atherosclerosis Risk in Communities Study; <b>BRHS</b>, British Regional Heart Study; <b>BWHHS</b>, British Women’s Heart and Health Study; <b>Caerphilly</b>, Caerphilly Prospective Study; <b>CHD</b>, coronary heart disease endpoint (composed of nonfatal myocardial infarction and coronary death); <b>CHS</b>, Cardiovascular Health Study; <b>CS</b>, coronary surgery; <b>DStago</b>, Diagnostica Stago; <b>EAS</b>, Edinburgh Artery Study; <b>ELISA</b>, enzyme-linked immunosorbent assay; <b>FHS</b>, Framingham Heart Study; <b>Fletcher</b>, Fletcher Challenge Study; <b>Glostrup</b>, Glostrup population studies; <b>IRE</b>, Ireland; <b>IT</b>, immunoturbidometry; <b>MESA</b>, Multi-Ethnic Study of Atherosclerosis; <b>MI</b>, myocardial infarction; <b>NPHS-I</b>, Northwick Park Heart Study I; <b>NSHDS</b>, Northern Sweden Health and Diseases Study cohort; <b>PHS</b>, Physicians’ Health Study; <b>PRIME</b>, Prospective Epidemiological Study of Myocardial Infarction; <b>PROSPER</b>, Prospective Study of Pravastatin in the Elderly at Risk; <b>NI</b>, Northern Ireland; <b>NL</b>, Netherlands; <b>NR</b>, not reported; <b>NZ</b>, New Zealand; <b>R&D Sys</b>, R&S Systems; <b>RE</b>, rocket electrophoresis; <b>Rotterdam</b>, Rotterdam Study; <b>SCO</b>, Scotland; <b>Speedwell</b>, Speedwell Study; <b>Three-City</b>, Three-City cohort study; <b>WHI</b>, Women’s Health Initiative; <b>WOSCOPS</b>, The West of Scotland Coronary Prevention Study.</p>*<p>Reports with two different study baselines and non-overlapping follow-up periods are available.</p>†<p>Median.</p>‡<p>Maximum.</p>§<p>Range.</p>||<p>Geometric mean.</p

Head-to-head comparison of associations of various baseline variables with coronary heart disease risk (Reykjavik Study).

<p>*Values were log_e transformed for analysis. †Adjusted for age, sex, period of recruitment, smoking status, body mass index, systolic blood pressure, history of diabetes, total cholesterol and log_e triglycerides.</p

Study flow diagram of the updated meta-analyses.

<p>The figure was designed based on the 2009 PRISMA flow diagram template (available from <a href="http://www.prisma-statement.org/statement.htm" target="_blank">http://www.prisma-statement.org/statement.htm</a>).</p

Association of baseline levels of t-PA antigen, D-dimer and VWF with coronary heart disease in the Reykjavik Study (1925 cases, 3616 controls).

*<p>Smoking status, body mass index, systolic blood pressure and any history of diabetes mellitus at baseline.</p>†<p>Total cholesterol and log_e triglycerides.</p><p>When analyses were restricted to participants with complete information on C-reactive protein (1906 cases, 3573 controls), the odds ratios (95% CI) per 1 SD higher value of t-PA antigen were 1.26 (1.18, 1.33) when adjusting for age, sex and period of recruitment, 1.15 (1.07, 1.22) when additionally adjusting for non-lipid risk factors, 1.07 (0.99, 1.14) when additionally adjusting for lipid risk factors and 1.04 (0.97, 1.11) when additionally adjusting for C-reactive protein. Corresponding odds ratios were 1.01 (0.95, 1.07), 1.04 (0.98, 1.11), 1.07 (1.00, 1.14) and 1.05 (0.99, 1.12) for D-dimer and 1.12 (1.05, 1.18), 1.09 (1.02, 1.15), 1.09 (1.03, 1.16) and 1.06 (1.00, 1.13) for VWF.</p

Meta-analyses of reported associations of t-PA antigen, D-dimer and VWF with coronary heart disease risk in prospective population-based studies.

<p>Study acronyms are explained in the legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055175#pone-0055175-t003" target="_blank"><b>Table 3</b></a>. Summary estimates were calculated using random effects models. *Degree of adjustment:+minimally adjusted (typically adjusted for age and sex only);++plus adjustment for at least one non-lipid marker;+++plus adjustment for at least one lipid marker;++++plus adjustment for at least one inflammatory marker. Where studies reported relative risks with more than one level of statistical adjustment, the most adjusted estimate was used (least adjusted estimates are reported in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055175#pone.0055175.s008" target="_blank">Figure S8</a></b>).</p