Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.

Background: Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods And Results: Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models.

Proteomic profiling identifies novel independent relationships between inflammatory proteins and myocardial infarction.

Background: Inflammation has been implicated in the pathogenesis of coronary heart disease, but the relevance and independence of individual inflammatory proteins is uncertain.

Objective: To examine the relationships between a spectrum of inflammatory proteins and myocardial infarction (MI).

Methods And Results: A panel of 92 inflammatory proteins was assessed using an OLINK multiplex immunoassay among 432 MI cases (diagnosed < 66 years) and 323 controls.

Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease.

Background: Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls).

Methods: The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use.

Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci.

Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.

Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.

Background: It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods: 311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci.

Oxidized phospholipids on apolipoprotein B-100 versus plasminogen and risk of coronary heart disease in the PROCARDIS study.

Background And Aims: Oxidized phospholipids carried on the apolipoprotein B-100 (OxPL-apoB) component of Lp(a) are predictive of coronary heart disease (CHD), but the role of oxidized phospholipids carried on plasminogen (OxPL-PLG) is unknown. We examined the independent effects of OxPL-apoB and OxPL-PLG for risk of CHD before and after adjustment for Lp(a).

Methods: Plasma levels of OxPL-apoB, OxPL-PLG, plasminogen and Lp(a) were measured in the PROCARDIS study of early-onset CHD (906 cases/858 controls).

Genetic associations of adult height with risk of cardioembolic and other subtypes of ischemic stroke: A mendelian randomization study in multiple ancestries.

Background: Taller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke.

Methods And Findings: Height-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations.

Are polygenic risk scores for systolic blood pressure and LDL-cholesterol associated with treatment effectiveness, and clinical outcomes among those on treatment?

Aims: Many studies have investigated associations between polygenic risk scores (PRS) and the incidence of cardiovascular disease (CVD); few have examined whether risk factor-related PRS predict CVD outcomes among adults treated with risk-modifying therapies. We assessed whether PRS for systolic blood pressure (PRSSBP) and for low-density lipoprotein cholesterol (PRSLDL-C) were associated with achieving SBP and LDL-C-related targets, and with major adverse cardiovascular events (MACE: non-fatal stroke or myocardial infarction, CVD death, and revascularization procedures).

Methods And Results: Using observational data from the UK Biobank (UKB), we calculated PRSSBP and PRSLDL-C and constructed two sub-cohorts of unrelated adults of White British ancestry aged 40-69 years and with no history of CVD, who reported taking medications used in the treatment of hypertension or hypercholesterolaemia.

The impact of atrial fibrillation and stroke risk factors on left atrial blood flow characteristics.

Aims: Altered left atrial (LA) blood flow characteristics account for an increase in cardioembolic stroke risk in atrial fibrillation (AF). Here, we aimed to assess whether exposure to stroke risk factors is sufficient to alter LA blood flow even in the presence of sinus rhythm (SR).

Methods And Results: We investigated 95 individuals: 37 patients with persistent AF, who were studied before and after cardioversion [Group 1; median CHA2DS2-VASc = 2.

Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes.

Type 2 diabetes (T2D) is an important heritable risk factor for coronary artery disease (CAD), the risk of both diseases being increased by metabolic syndrome (MS). With the availability of large-scale genome-wide association data, we aimed to elucidate the genetic burden of CAD risk in T2D predisposed individuals within the context of MS and their shared genetic architecture. Mendelian randomization (MR) analyses supported a causal relationship between T2D and CAD [odds ratio (OR) = 1.

Genome-Wide Association Study of Peripheral Artery Disease.

Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status.

Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings.

Smoking and COVID-19 outcomes: an observational and Mendelian randomisation study using the UK Biobank cohort.

Background: Conflicting evidence has emerged regarding the relevance of smoking on risk of COVID-19 and its severity.

Methods: We undertook large-scale observational and Mendelian randomisation (MR) analyses using UK Biobank. Most recent smoking status was determined from primary care records (70.

Independent effects of adiposity measures on risk of atrial fibrillation in men and women: a study of 0.5 million individuals.

Background: Atrial fibrillation (AF) has a higher prevalence in men than in women and is associated with measures of adiposity and lean mass (LM). However, it remains uncertain whether the risks of AF associated with these measures vary by sex.

Methods: Among 477 904 UK Biobank participants aged 40-69 without prior AF, 23 134 incident AF cases were identified (14 400 men, 8734 women; median follow-up 11.

Assessment of the causal relevance of ECG parameters for risk of atrial fibrillation: A mendelian randomisation study.

Background: Atrial electrical and structural remodelling in older individuals with cardiovascular risk factors has been associated with changes in surface electrocardiographic (ECG) parameters (e.g., prolongation of the PR interval) and higher risks of atrial fibrillation (AF).

The Use of Primary Care Big Data in Understanding the Pharmacoepidemiology of COVID-19: A Consensus Statement From the COVID-19 Primary Care Database Consortium.

The use of big data containing millions of primary care medical records provides an opportunity for rapid research to help inform patient care and policy decisions during the first and subsequent waves of the coronavirus disease 2019 (COVID-19) pandemic. Routinely collected primary care data have previously been used for national pandemic surveillance, quantifying associations between exposures and outcomes, identifying high risk populations, and examining the effects of interventions at scale, but there is no consensus on how to effectively conduct or report these data for COVID-19 research. A COVID-19 primary care database consortium was established in April 2020 and its researchers have ongoing COVID-19 projects in overlapping data sets with over 40 million primary care records in the United Kingdom that are variously linked to public health, secondary care, and vital status records.

Independent risk factors for simvastatin-related myopathy and relevance to different types of muscle symptom.

Aims: Statins are widely used to prevent cardiovascular events, but little is known about the impact of different risk factors for statin-related myopathy or their relevance to reports of other types of muscle symptom.

Methods And Results: An observational analysis was undertaken of 171 clinically adjudicated cases of myopathy (defined as unexplained muscle pain or weakness with creatine kinase >10× upper limit of normal) and, separately, of 15 208 cases of other muscle symptoms among 58 390 individuals with vascular disease treated with simvastatin for a mean of 3.4 years.

Identification of patients with atrial fibrillation: a big data exploratory analysis of the UK Biobank.

Objective: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence of around 1.6% in the adult population. The analysis of the electrocardiogram (ECG) data acquired in the UK Biobank represents an opportunity to screen for AF in a large sub-population in the UK.

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol.

Blood lipids are causally involved in the pathogenesis of atherosclerosis, but their role in cerebral small vessel disease remains largely elusive. Here, we explored associations of genetic determinants of blood lipid levels, lipoprotein particle components, and targets for lipid-modifying drugs with small vessel disease phenotypes. We selected genetic instruments for blood levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, for cholesterol and triglycerides components of size-defined lipoprotein particles, and for lipid-modifying drug targets based on published genome-wide association studies (up to 617 303 individuals).

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.

Methods: Published and individual 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.

Cardiovascular care of patients with stroke and high risk of stroke: The need for interdisciplinary action: A consensus report from the European Society of Cardiology Cardiovascular Round Table.

Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention.