Abstract
Aims
The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged ...over 70 years in four geographical risk regions.
Methods and results
Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations {338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 95% confidence interval (CI) 0.61–0.65 and 0.67 (0.64–0.69)}. Regional calibration of expected-vs.-observed risks was satisfactory. For given risk factor profiles, there was substantial variation across the four risk regions in the estimated 10-year CVD event risk.
Conclusions
The competing risk-adjusted SCORE2-OP model was derived, recalibrated, and externally validated to estimate 5- and 10-year CVD risk in older adults (aged 70 years or older) in four geographical risk regions. These models can be used for communicating the risk of CVD and potential benefit from risk factor treatment and may facilitate shared decision-making between clinicians and patients in CVD risk management in older persons.
Graphical Abstract
Development process, risk regions and illustrative example for the SCORE2-OP algorithm.
Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk ...factors in the primary prevention of CVD.
Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age SD: 56.0 8.0 years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703-0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009-0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40-75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation.
Our results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.
To provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with ...age- and sex- specific risk thresholds.
eHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40-69 years in a population in England for invitation to a formal CVD risk assessment.
Formal CVD risk assessment on all adults would identify 76% and 49% of future CVD events amongst men and women respectively, and 93 (95% CI: 90, 95) men and 279 (95% CI: 259, 297) women would need to be screened (NNS) to prevent one CVD event. In contrast, if eHEART was first used to prioritise individuals for formal CVD risk assessment, we would identify 73% and 47% of future events amongst men and women respectively, and a NNS of 75 (95% CI: 72, 77) men and 162 (95% CI: 150, 172) women. Replacing the age- and sex-specific prioritisation thresholds with a 10% threshold identify around 10% less events.
The use of prioritisation tools with age- and sex-specific thresholds could lead to more efficient CVD assessment programmes with only small reductions in effectiveness at preventing new CVD events.
Metabolic biomarker data quantified by nuclear magnetic resonance (NMR) spectroscopy in approximately 121,000 UK Biobank participants has recently been released as a community resource, comprising ...absolute concentrations and ratios of 249 circulating metabolites, lipids, and lipoprotein sub-fractions. Here we identify and characterise additional sources of unwanted technical variation influencing individual biomarkers in the data available to download from UK Biobank. These included sample preparation time, shipping plate well, spectrometer batch effects, drift over time within spectrometer, and outlier shipping plates. We developed a procedure for removing this unwanted technical variation, and demonstrate that it increases signal for genetic and epidemiological studies of the NMR metabolic biomarker data in UK Biobank. We subsequently developed an R package, ukbnmr, which we make available to the wider research community to enhance the utility of the UK Biobank NMR metabolic biomarker data and to facilitate rapid analysis.
Surprisingly few attempts have been made to quantify the simultaneous contribution of well-established risk factors to CVD mortality differences between countries. We aimed to develop and critically ...appraise an approach to doing so, applying it to the substantial CVD mortality gap between Russia and Norway using survey data in three cities and mortality risks from the Emerging Risk Factor Collaboration. We estimated the absolute and relative differences in CVD mortality at ages 40-69 years between countries attributable to the risk factors, under the counterfactual that the age- and sex-specific risk factor profile in Russia was as in Norway, and vice-versa. Under the counterfactual that Russia had the Norwegian risk factor profile, the absolute age-standardized CVD mortality gap would decline by 33.3% (95% CI 25.1-40.1) among men and 22.1% (10.4-31.3) among women. In relative terms, the mortality rate ratio (Russia/Norway) would decline from 9-10 to 7-8. Under the counterfactual that Norway had the Russian risk factor profile, the mortality gap reduced less. Well-established CVD risk factors account for a third of the male and around a quarter of the female CVD mortality gap between Russia and Norway. However, these estimates are based on widely held epidemiological assumptions that deserve further scrutiny.
Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular ...disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.
This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a ...multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 95%CI 1.22-2.12 and 1.46 95%CI 1.09-1.97, respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 95%CI 1.15-6.55), right-bundle branch block (HR 2.09 95%CI 1.02-4.29), and second-degree heart block (HR 2.45 95%CI 0.59-10.16). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.
During recent decades, Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases. Coronary heart disease (CHD), with myocardial infarction (MI) as ...its main manifestation, is a major cause of death in the country. However, there is limited reliable evidence about its determinants in this population. The Bangladesh Risk of Acute Vascular Events (BRAVE) study is an epidemiological bioresource established to examine environmental, genetic, lifestyle and biochemical determinants of CHD among the Bangladeshi population. By early 2015, the ongoing BRAVE study had recruited over 5000 confirmed first-ever MI cases, and over 5000 controls "frequency-matched" by age and sex. For each participant, information has been recorded on demographic factors, lifestyle, socioeconomic, clinical, and anthropométrie characteristics. A 12-lead electrocardiogram has been recorded. Biological samples have been collected and stored, including extracted DNA, plasma, serum and whole blood. Additionally, for the 3000 cases and 3000 controls initially recruited, genotyping has been done using the CardioMetabochip+ and the Exome-h arrays. The mean age (standard deviation) of MI cases is 53 (10) years, with 88 % of cases being male and 46 % aged 50 years or younger. The median interval between reported onset of symptoms and hospital admission is 5 h. Initial analyses indicate that Bangladeshis are genetically distinct from major non-South Asian ethnicities, as well as distinct from other South Asian ethnicities. The BRAVE study is well-placed to serve as a powerful resource to investigate current and future hypotheses relating to environmental, biochemical and genetic causes of CHD in an important but under-studied South Asian population.
It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVDs).
To characterize the association between depressive symptoms and CVD ...incidence across the spectrum of lower mood.
A pooled analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 162 036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and the UK Biobank (401 219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline.
Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Center for Epidemiological Studies Depression (CES-D) scale (range, 0-60; ≥16 indicates possible depressive disorder). The UK Biobank recorded the 2-item Patient Health Questionnaire 2 (PHQ-2; range, 0-6; ≥3 indicates possible depressive disorder).
Primary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the 2). Hazard ratios (HRs) per 1-SD higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported.
Among 162 036 participants from the ERFC (73%, women; mean age at baseline, 63 years SD, 9 years), 5078 CHD and 3932 stroke events were recorded (median follow-up, 9.5 years). Associations with CHD, stroke, and CVD were log linear. The HR per 1-SD higher depression score for CHD was 1.07 (95% CI, 1.03-1.11); stroke, 1.05 (95% CI, 1.01-1.10); and CVD, 1.06 (95% CI, 1.04-1.08). The corresponding incidence rates per 10 000 person-years of follow-up in the highest vs the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs 1) were 36.3 vs 29.0 for CHD events, 28.0 vs 24.7 for stroke events, and 62.8 vs 53.5 for CVD events. Among 401 219 participants from the UK Biobank (55% were women, mean age at baseline, 56 years SD, 8 years), 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1 years). The HR per 1-SD higher depression score for CHD was 1.11 (95% CI, 1.08-1.14); stroke, 1.10 (95% CI, 1.06-1.14); and CVD, 1.10 (95% CI, 1.08-1.13). The corresponding incidence rates per 10 000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher vs 0 were 20.9 vs 14.2 for CHD events, 15.3 vs 10.2 for stroke events, and 36.2 vs 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors.
In a pooled analysis of 563 255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.
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