Conventional Risk Factors For Prediction Research Articles

Lifetime and 10-year risks of cardiovascular mortality in relation to risk factors in middle and old age: 50-year follow-up of the Whitehall study of London Civil Servants

BackgroundCardiovascular disease (CVD)-related mortality has declined substantially in the United Kingdom (UK) in recent decades, but the continued relevance of conventional risk factors for prediction of CVD mortality throughout the life-course is uncertain. We compared the 10-year risks and lifetime risks of CVD mortality associated with conventional risk factors recorded in middle and old age. MethodsThe Whitehall study was a prospective study of 19,019 male London civil servants (mean age 52 years) when enrolled in 1967–1970 and followed-up for 50 years for cause-specific mortality. In 1997, 7044 (83%) survivors (mean age 77 years) were re-surveyed. The 10-year and lifetime risks of CVD mortality were estimated by levels of CVD risk factors recorded in middle-age and old-age, respectively. ResultsBy July 2020, 97% had died (22%, 51% and 80% before age 70, 80 and 90 years, respectively) and 7944 of 17,673 deaths (45%) were from CVD. The 10-year and lifetime risks of CVD death increased linearly with higher levels of CVD risk factors recorded in middle-age and in old-age. Individuals in the top versus bottom 5% of CVD risk scores in middle age had a 10.3% (95% CI:7.2–13.4) vs 0.6% (0.1–1.2) 10-year risk of CVD mortality, a 61.4% (59.4–65.3) vs 31.3% (24.1–34.5) lifetime risk of CVD mortality and a 12-year difference in life expectancy from age 50 years. The corresponding differences using a CVD risk score in old-age were 11.0% (4.4–17.5) vs 0.8% (0.0–2.2) for 10-year risk and 42.1% (28.2–50.0) vs 30.3% (6.0–38.0) for lifetime risk of CVD mortality and a 6-year difference in life expectancy from age 70 years. ConclusionsConventional risk factors remained highly predictive of CVD mortality and life expectancy through the life-course. The findings highlight the relevance of estimation of both lifetime risks of CVD and 10-year risks of CVD for primary prevention of CVD.

Importance of NT-proBNP and conventional risk factors for prediction of death in older adults with and without diabetes mellitus– A report from the Atherosclerosis Risk in Communities (ARIC) study

In this community-based cohort of 5861 individuals followed for median 7.2 years, the discriminatory ability of NT-proBNP alone in predicting mortality was similar to that of multiple conventional markers of risk in people without diabetes. In people with diabetes, NT-proBNP alone discriminated risk of mortality better than conventional risk factors.

Early prediction of incident liver disease using conventional risk factors and gut-microbiome-augmented gradient boosting

SummaryThe gut microbiome has shown promise as a predictive biomarker for various diseases. However, the potential of gut microbiota for prospective risk prediction of liver disease has not been assessed. Here, we utilized shallow shotgun metagenomic sequencing of a large population-based cohort (N > 7,000) with ∼15 years of follow-up in combination with machine learning to investigate the predictive capacity of gut microbial predictors individually and in conjunction with conventional risk factors for incident liver disease. Separately, conventional and microbial factors showed comparable predictive capacity. However, microbiome augmentation of conventional risk factors using machine learning significantly improved the performance. Similarly, disease-free survival analysis showed significantly improved stratification using microbiome-augmented models. Investigation of predictive microbial signatures revealed previously unknown taxa for liver disease, as well as those previously associated with hepatic function and disease. This study supports the potential clinical validity of gut metagenomic sequencing to complement conventional risk factors for prediction of liver diseases.

Improving prediction of atrial fibrillation: the impact of polygenic risk scores over conventional risk factors amongst 270,000 individuals in UK Biobank

Abstract Background Previous studies have suggested only modest benefits of adding genetic information to conventional risk factors for prediction of atrial fibrillation (AF). However, these studies have been based on limited numbers of AF cases and pre-date recent AF genetic discoveries. Purpose To examine the independent relevance of common genetic risk factors over and above established non-genetic risk factors for predicting AF amongst 270,000 participants from UK Biobank, and to determine potential clinical utility. Methods UK Biobank (UKB) is a large prospective study of over 500,000 British individuals aged 40 to 69 years at recruitment. Incident AF was ascertained using hospital episode statistics and death registry data. The CHARGE-AF score, which combines the relevance of age, height, weight, blood pressure, use of antihypertensives, diabetes, heart failure, and myocardial infarction (MI) was used to estimate 5-year risk of AF at baseline. A polygenic risk score (PRS) was constructed based on 142 independent variants previously associated with AF in a genome-wide meta-analysis of 60,620 AF cases from the AFGen Consortium, weighted by their published effect sizes. A total of 270,254 individuals were analysed after exclusions for genetic QC, non-White British ancestry, and prevalent AF. Cox proportional hazard models were used to estimate associations between risk scores (based on standard deviation [SD] units) and incident AF. Standard methods were used to assess predictive value. Results During a median follow-up of 8.1 years, 12,407 incident AF cases were identified. The CHARGE-AF risk score strongly predicted incident AF in UK Biobank, and was associated with a ∼3-fold higher risk of AF per SD (Hazard ratio [HR]=2.88; 95% CI: 2.82–2.94). The PRS was associated with a 54% higher risk of AF per SD (HR=1.54; 95% CI: 1.51–1.57). The independent impact of the PRS, after adjusting for the CHARGE-AF score, was unchanged and remained strongly predictive (HR=1.57, 95% CI: 1.54–1.60), with participants in the upper tertile of the PRS having more than a 2.5-fold higher risk (HR=2.59, 95% CI: 2.47–2.71) when compared with those in the lower tertile. The addition of the PRS improved the C-statistic from 0.758 (CHARGE-AF alone) to 0.783 (Δ=0.025) and correctly reclassified 8.7% of cases and 2.6% of controls at 5 years. Both non-genetic and genetic risk scores were well-calibrated in the UK Biobank participants, and sensitivity of the results to alternative PRS selection approaches and age at risk were also examined. Conclusion In a large prospective cohort, genetic determinants of AF were independent of conventional risk factors and significantly improved prediction over a well-validated clinical risk algorithm. This illustrates the potential added benefit of genetic information to identify higher-risk individuals who may benefit from earlier monitoring and personalised risk management strategies. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Sex-Specific Metabolite Biomarkers of NAFLD in Youth: A Prospective Study in the EPOCH Cohort

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed nations. There are currently no accurate biomarkers of NAFLD risk in youth. Identify sex-specific metabolomics biomarkers of NAFLD in a healthy cohort of youth. This prospective study included 395 participants of the EPOCH cohort in Colorado, who were recruited 2006-2009 ("T1 visit") and followed for 5 years ("T2 visit"). We entered 767 metabolites measured at T1 into a reduced rank regression model to identify the strongest determinants of hepatic fat fraction (HFF) at T2, separately for boys and girls. We compared the capacity of metabolites versus conventional risk factors (overweight/obesity, insulin, alanine transaminase, aspartate transaminase) to predict NAFLD (HFF ≥5%) and high HFF (fourth vs first quartile) using area under the receiver operating characteristic curve (AUC). Prevalence of NAFLD was 7.9% (8.5% of boys, 7.1% of girls). Mean ± SD HFF was 2.5 ± 3.1%. We identified 13 metabolites in girls and 10 metabolites in boys. Metabolites were in lipid, amino acid, and carbohydrate metabolism pathways. At T1, the metabolites outperformed conventional risk factors in prediction of high HFF but not NAFLD. At T2, the metabolites were superior to conventional risk factors as predictors of high HFF (AUC for metabolites vs conventional risk factors for boys: 0.9565 vs 0.8851, P = 0.02; for girls: 0.9450 vs 0.8469, P = 0.02) with similar trends for NAFLD, although the differences were not significant. The metabolite profiles identified herein are superior predictors of high HFF when assessed 5 years prior and concurrently in a general-risk setting.

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium.

AimsOur aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.Methods and resultsBased on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals <6 ng/L of troponin I, whereas the relative risk reduction was similar.ConclusionIn individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

Serum NOX2 and urinary isoprostanes predict vascular events in patients with atrial fibrillation

There are limited prospective data evaluating the role of urinary F2-IsoP and NOX2 as predictive markers in atrial fibrillation (AF). The aim of this study was to analyse the role of urinary prostaglandin PGF2alpha (8-iso-PGF2α) and NOX2, markers of systemic oxidative stress, in predicting cardiovascular (CV) events and mortality in anticoagulated non-valvular AF patients. This was a prospective study including 1,002 anticoagulated AF patients, followed for a median time of 25.7 months (interquartile range: 14.8-50.9). All major CV events, CV deaths and all-cause deaths were considered as primary outcomes of the study. CV events included fatal/nonfatal ischaemic stroke, fatal/nonfatal myocardial infarction (MI), cardiac revascularisation and transient ischaemic attack (TIA). Oxidative stress biomarkers, such as urinary 8-iso-PGF2α and serum sNOX2-dp, a marker of NOX2 activation, were measured. A CV event occurred in 125 patients (12.5 %); 78 CV deaths and 31 non-CV deaths were registered. 8-iso-PGF2α and sNOX2-dp were correlated (Rs=0.765 p< 0.001). A significant increased cumulative incidence of CV events and CV deaths was observed across tertiles for 8-iso-PGF2α and sNOX2-dp. An increased rate of all-cause death was observed across tertiles of urinary 8-iso-PGF2α. In Cox or Fine and Gray models, 8-iso-PGF2α predicted CV events and CV and non-CV deaths. The addition of tertiles of 8-iso-PGF2α to CHA2DS2-VASc score improved ROC curves for each outcome and NRI for CV events (0.24 [0.06-0.53] p=0.0067). The study shows that in AF patients 8-iso-PGF2α and NOX2 levels are predictive of CV events and total mortality. F2-IsoP may complement conventional risk factors in prediction of CV events.

Improvement in prediction of coronary heart disease risk over conventional risk factors using SNPs identified in genome-wide association studies.

ObjectiveWe examined whether a panel of SNPs, systematically selected from genome-wide association studies (GWAS), could improve risk prediction of coronary heart disease (CHD), over-and-above conventional risk factors. These SNPs have already demonstrated reproducible associations with CHD; here we examined their use in long-term risk prediction.Study Design and SettingSNPs identified from meta-analyses of GWAS of CHD were tested in 840 men and women aged 55–75 from the Edinburgh Artery Study, a prospective, population-based study with 15 years of follow-up. Cox proportional hazards models were used to evaluate the addition of SNPs to conventional risk factors in prediction of CHD risk. CHD was classified as myocardial infarction (MI), coronary intervention (angioplasty, or coronary artery bypass surgery), angina and/or unspecified ischaemic heart disease as a cause of death; additional analyses were limited to MI or coronary intervention. Model performance was assessed by changes in discrimination and net reclassification improvement (NRI).ResultsThere were significant improvements with addition of 27 SNPs to conventional risk factors for prediction of CHD (NRI of 54%, P<0.001; C-index 0.671 to 0.740, P = 0.001), as well as MI or coronary intervention, (NRI of 44%, P<0.001; C-index 0.717 to 0.750, P = 0.256). ROC curves showed that addition of SNPs better improved discrimination when the sensitivity of conventional risk factors was low for prediction of MI or coronary intervention.ConclusionThere was significant improvement in risk prediction of CHD over 15 years when SNPs identified from GWAS were added to conventional risk factors. This effect may be particularly useful for identifying individuals with a low prognostic index who are in fact at increased risk of disease than indicated by conventional risk factors alone.

Coagulation factors, activation markers and risk of coronary heart disease: the Northwick Park Heart Studies.

Coagulation factors, activation markers and risk of coronary heart disease: the Northwick Park Heart Studies.

Arterial compliance adds to conventional risk factors for prediction of angiographic coronary artery disease

Background Arterial compliance is related to left ventricular hypertrophy and risk for cardiovascular disease events; however, its association with coronary artery stenosis remains uncertain. We sought to assess the relation between lower extremity arterial compliance and presence of angiographically defined coronary artery disease. Methods Lower extremity arterial compliance was measured with the use of a noninvasive air plethysmography technique in 376 subjects undergoing routine diagnostic coronary angiography. Results Measures of calf arterial compliance were significantly associated with the presence of one or more stenoses ≥50% compared with no stenoses, even after adjustment for age, sex, smoking, diabetes, hypertension, hypercholesterolemia, and obesity ( P = .03). Measures of thigh arterial compliance were also lower in subjects with disease, although this association did not reach statistical significance ( P = .07). Receiver operator curves illustrate the incremental predictive ability of calf arterial compliance over and above age, sex, and conventional risk factors. Conclusions Lower extremity arterial compliance is associated with presence of significant coronary stenoses in a cardiac catheterization laboratory referral population. This observation lends support for additional efforts to determine the utility of vascular stiffness measures in both clinical and pre-clinical populations to guide treatment and prevention efforts.