ORCID Profile
0000-0003-3139-1836
Current Organisation
University of Oxford
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Publisher: Elsevier BV
Date: 02-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-08-2020
DOI: 10.1161/CIRCULATIONAHA.120.046361
Abstract: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87–0.94), with an additional relative risk for CVD of 0.92 (0.87–0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75–0.93), 0.76 (0.67–0.85), 0.69 (0.59–0.79), or 0.63 (0.52–0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of in idual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Oxford University Press (OUP)
Date: 11-2018
DOI: 10.1373/CLINCHEM.2018.292086
Abstract: Few data compare cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in a general population. We sought to evaluate the distribution and association between cTnT, cTnI, and cardiovascular risk factors in a large general population cohort. High-sensitivity cTnT and cTnI were measured in serum from 19501 in iduals in the Generation Scotland Scottish Family Health Study. Associations with cardiovascular risk factors were compared using age- and sex-adjusted regression. Observed age- and sex-stratified 99th centiles were compared with 99th centiles for cTnT (men, 15.5 ng/L women, 9.0 ng/L) and cTnI (men, 34.2 ng/L women, 15.6 ng/L) used in clinical practice. cTnT and cTnI concentrations were detectable in 53.3% and 74.8% of participants, respectively, and were modestly correlated in unadjusted analyses (R2 = 21.3%) and only weakly correlated after adjusting for age and sex (R2 = 9.5%). Cardiovascular risk factors were associated with both troponins, but in age- and sex-adjusted analyses, cTnI was more strongly associated with age, male sex, body mass index, and systolic blood pressure (P & 0.0001 for all vs cTnT). cTnT was more strongly associated with diabetes (P & 0.0001 vs cTnI). The observed 99th centiles were broadly consistent with recommended 99th centiles in younger men and women. After the age of 60 years, observed 99th centiles increased substantially for cTnT, and beyond 70 years of age, the 99th centiles approximately doubled for both troponins. In the general population, cTnT and cTnI concentrations are weakly correlated and are differentially associated with cardiovascular risk factors. The 99th centiles currently in use are broadly appropriate for men and women up to but not beyond the age of 60 years.
Publisher: Elsevier BV
Date: 11-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-06-2019
DOI: 10.1161/CIRCULATIONAHA.118.038529
Abstract: There is great interest in widening the use of high-sensitivity cardiac troponins for population cardiovascular disease (CVD) and heart failure screening. However, it is not clear whether cardiac troponin T (cTnT) and troponin I (cTnI) are equivalent measures of risk in this setting. We aimed to compare and contrast (1) the association of cTnT and cTnI with CVD and non-CVD outcomes, and (2) their determinants in a genome-wide association study. High-sensitivity cTnT and cTnI were measured in serum from 19 501 in iduals in Generation Scotland Scottish Family Health Study. Median follow-up was 7.8 years (quartile 1 to quartile 3, 7.1–9.2). Associations of each troponin with a composite CVD outcome (1177 events), CVD death (n=266), non-CVD death (n=374), and heart failure (n=216) were determined by using Cox models. A genome-wide association study was conducted using a standard approach developed for the cohort. Both cTnI and cTnT were strongly associated with CVD risk in unadjusted models. After adjusting for classical risk factors, the hazard ratio for a 1 SD increase in log transformed troponin was 1.24 (95% CI, 1.17–1.32) and 1.11 (1.04–1.19) for cTnI and cTnT, respectively ratio of hazard ratios 1.12 (1.04–1.21). cTnI, but not cTnT, was associated with myocardial infarction and coronary heart disease. Both cTnI and cTnT had strong associations with CVD death and heart failure. By contrast, cTnT, but not cTnI, was associated with non-CVD death ratio of hazard ratios 0.77 (0.67–0.88). We identified 5 loci (53 in idual single-nucleotide polymorphisms) that had genome-wide significant associations with cTnI, and a different set of 4 loci (4 single-nucleotide polymorphisms) for cTnT. The upstream genetic causes of low-grade elevations in cTnI and cTnT appear distinct, and their associations with outcomes also differ. Elevations in cTnI are more strongly associated with some CVD outcomes, whereas cTnT is more strongly associated with the risk of non-CVD death. These findings help inform the selection of an optimal troponin assay for future clinical care and research in this setting.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2019
DOI: 10.1186/S12872-019-1187-Z
Abstract: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Published and in idual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57 1.22) for the GS, compared to 0.85 (95% CI 0.78 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11 1.50) for the GS, as compared to 1.00 (95% CI 0.96 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown although precision was moderate.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Preiss.