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Opportunistic cardiovascular risk assessment and management in specialist settings can have a major long‐term impact on patients’ health and quality of life. At its core the process is simple and feasible to deploy in all clinical settings, as the author explains.

ObjectiveEvidence on sex differences in outcomes after developing coronary heart disease (CHD) has focused on recurrent CHD, all-cause mortality or revascularisation. We assessed sex disparities in subsequent major adverse cardiovascular events (MACE) in adults surviving their first-time CHD.MethodsUsing a population-based cohort obtained from the Clinical Practice Research Datalink (CPRD GOLD) linked to hospitalisation and death records in the UK, we identified 143 702 adults (aged ≥18 years) between 1 January 1998 and 31 December 2017 with no prior history of MACE. MACE outcome was a composite of recurrent CHD, stroke, peripheral vascular disease, heart failure and cardiovascular-related mortality. Multivariable models (Cox and competing risks regressions) were used to assess differences between sexes.ResultsThere were 143 702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63 078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91 706 (63.8%). Women had a significantly lower risk of MACE (hazard ratio (HR), 0.68 (95% CI 0.67 to 0.69); sub-hazard ratio (HRsd), 0.71 (0.70 to 0.72), respectively) and recurrent CHD (n=66 543, 46.3%) (HR, 0.60 (0.59 to 0.61); HRsd, 0.62 (0.61 to 0.63)) when compared with men after incident CHD. However, women had a significantly higher risk of stroke (n=5740, 4.0%) (HR, 1.26 (1.19 to 1.33); HRsd, 1.32 (1.25 to 1.39)), heart failure (n=7905, 5.5%) (HR, 1.09 (1.04 to 1.15); HRsd, 1.13 (1.07 to 1.18)) and all-cause mortality (n=29 503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).ConclusionsAfter incident CHD, women have lower risk of composite MACE and recurrent CHD outcomes but higher risk of stroke, heart failure, and all-cause mortality compared with men.

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ObjectiveThe Familial Hypercholesterolaemia Case Ascertainment Tool (FAMCAT) has been proposed to enhance case finding in primary care. In this study, we test application of the FAMCAT algorithm to describe risks of familial hypercholesterolaemia (FH) in a large unselected and ethnically diverse primary care cohort.MethodWe studied patients aged 18–65 years from three contiguous areas in inner London. We retrospectively applied the FAMCAT algorithm to routine primary care data and estimated the numbers of possible cases of FH and the potential service implications of subsequent investigation and management.ResultsOf the 777 128 patients studied, the FAMCAT score estimated between 11 736 and 23 798 (1.5%–3.1%) individuals were likely to have FH, depending on an assumed FH prevalence of 1 in 250 or 1 in 500, respectively. There was over-representation of individuals of South Asian ethnicity among those likely to have FH, with this cohort making up 41.9%–45.1% of the total estimated cases, a proportion which significantly exceeded their 26% representation in the study population.ConclusionsWe have demonstrated feasibility of application of the FAMCAT as an aid to case finding for FH using routinely recorded primary care data. Further research is needed on validity of the tool in different ethnic groups and more refined consideration of family history should be explored. While FAMCAT may aid case finding, implementation requires information on the cost-effectiveness of additional health services to investigate, diagnose and manage case ascertainment in those identified as likely to have FH.

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IntroductionLung cancer screening (LCS) by low-dose computed tomography (LDCT) offers an opportunity to impact both lung cancer and coronary heart disease mortality through detection of coronary artery calcification (CAC). Here, we explore the value of CAC and cardiovascular disease (CVD) risk assessment in LCS participants in the Lung Screen Uptake Trial (LSUT).MethodsIn this cross-sectional study, current and ex-smokers aged 60–75 were invited to a ‘lung health check’. Data collection included a CVD risk assessment enabling estimation of 10 year CVD risk using the QRISK2 score. Participants meeting the required lung cancer risk underwent an ungated, non-contrast LDCT. Descriptive data, bivariate associations and a multivariate analysis of predictors of statin use are presented.ResultsOf 1005 individuals enrolled, 680 were included in the final analysis. 421 (61.9%) had CAC present and in 49 (7.2%), this was heavy. 668 (98%) of participants had a QRISK2≥10% and QRISK2 was positively associated with increasing CAC grade (OR 4.29 (CI 0.93 to 19.88) for QRISK2=10%–20% and 12.29 (CI 2.68 to 56.1) for QRISK2≥20% respectively). Of those who qualified for statin primary prevention (QRISK2≥10%), 56.8% did not report a history of statin use. In the multivariate analysis statin use was associated with age, body mass index and history of hypertension and diabetes.ConclusionsLCS offers an important opportunity for instituting CVD risk assessment in all LCS participants irrespective of the presence of LDCT-detected CAC. Further studies are needed to determine whether CAC could enhance uptake and adherence to primary preventative strategies.

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10−8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; ncases= 10,801) as well as a stricter definition without angina (HARD; ncases= 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.

Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPAgenetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.

Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.

Sequence variants affecting blood lipids and coronary artery disease (CAD) may enhance understanding of the atherogenicity of lipid fractions. Using a large resource of whole-genome sequence data, we examined rare and low-frequency variants for association with non-HDL cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides in up to 119,146 Icelanders. We discovered 13 variants with large effects (within ANGPTL3, APOB, ABCA1, NR1H3, APOA1, LIPC, CETP, LDLR, and APOC1) and replicated 14 variants. Five variants within PCSK9, APOA1, ANGPTL4, and LDLR associate with CAD (33,090 cases and 236,254 controls). We used genetic risk scores for the lipid fractions to examine their causal relationship with CAD. The non-HDL cholesterol genetic risk score associates most strongly with CAD (P = 2.7 × 10−28), and no other genetic risk score associates with CAD after accounting for non-HDL cholesterol. The genetic risk score for non-HDL cholesterol confers CAD risk beyond that of LDL cholesterol (P = 5.5 × 10−8), suggesting that targeting atherogenic remnant cholesterol may reduce cardiovascular risk.

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Context:The diagnosis of metabolic syndrome (MetS) identifies individuals at risk for developing diabetes and cardiovascular disease. African Americans (AAs) have high rates of cardiovascular disease and subclinical vascular disease including arterial stiffness and microvascular dysfunction but have relatively low rates of MetS.Objective:The objective of the study was to evaluate the relationship between MetS and vascular function in a biracial cohort with the hypothesis that the diagnosis of MetS underestimates subclinical vascular disease in AAs.Design:We measured components of MetS in a community-based cohort of 951 AAs and white subjects (aged 48.8 ± 11 y, 47% AA, 55% female).Main Outcome Measures:Using digital pulse amplitude tonometry, we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function. Using applanation tonometry (Sphygmocor), central augmentation index (CAIx) and pulse wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively.Results:MetS was present in 24.0% of subjects and was associated with increased PWV (P< .001) and CAIx (P< .001) and a trend to lower RHI (P= .068) in both races. However, in subjects without MetS, AAs had lower RHI (P< .001) and higher PWV (P= .003) and CAIx (P= .002) compared with white subjects. Addition of an extra MetS criterion point for AAs with hypertension eliminated the racial differences in PWV and CAIx but not RHI.Conclusion:Although MetS is associated with microvascular dysfunction and increased arterial stiffness in both racial groups, AAs without MetS have greater vascular dysfunction compared with whites. Additional weighting for hypertension in AAs attenuated the racial differences in subclinical disease associated with MetS.

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Studies in animal models have demonstrated that the protease ADAMTS7 plays a role in neointima formation after arterial mechanical injury, by facilitating vascular smooth muscle cell (VSMC) migration. Furthermore, recent human genetic studies have revealed an association between DNA polymorphisms at the ADAMTS7gene locus and risk of coronary artery disease (CAD). Functional studies have shown that a CAD-associated polymorphism in the coding region of the ADAMTS7gene affects ADAMTS7 maturation and VSMC migration. This editorial highlights these findings and discusses targeted ADAMTS7 inhibition as a possible novel approach to treat CAD.

Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established.

We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis.

Introduction:Excessive stiffening of the highly elastic aorta relative to the carotid artery may reduce impedance mismatch at their bifurcation and increase transmission of potentially-damaging pulsatile energy towards the fragile microcirculation of the brain.Hypothesis:Accelerated stiffening of the aorta relative to carotid artery stiffness will be associated with an increased rate of cognitive decline over long-term follow-up.Methods:Carotid stiffness, aortic stiffness, and cognitive function were available in 2248 individuals aged 58-74 years taking part in the Whitehall II Study. Carotid stiffness (pulse wave velocity [PWV] calculated using Bramwell-Hill equation) was assessed on a single occasion between 2002-2004 using duplex Doppler ultrasound, whereas rate of aortic stiffening (change in carotid-femoral PWV per year; ?PWV/year) was assessed on two occasions between 2007-2013 using applanation tonometry. Cognitive function - assessed using a global z-score incorporating multiple cognitive domains - was measured on up to four occasions between 2002-2016.Results:Mean (SD) 10-year change in standardized global cognitive score was -0.38(0.19). In multivariable models adjusting for a wide-range of potential confounders, accelerated aortic stiffening was associated with an increased rate of cognitive decline (change in 10 year cognitive score [95%CI] per 1SD increased ?PWV/year = -0.011 [-0.018,-0.003]; p=0.006). In contrast, individuals with a stiffer carotid artery at baseline showed some evidence of a slower rate of decline following adjustment for aortic stiffness (0.006 [-0.001,0.013]; p=0.114). As a result, individuals with higher rates of aortic stiffening demonstrated an increased risk of developing the most rapid cognitive decline (categorized as top 15% of cohort) during follow-up (Odds Ratio per 1SD increase = 1.12 [1.01,1.26]), whereas those with higher carotid stiffness had a reduced risk (Odds Ratio = 0.87 [0.77,0.99]).Conclusions:Accelerated aortic stiffening relative to carotid stiffness in mid- to late-life may be important in the pathogenesis and transmission of high intensity arterial waves towards the cerebral circulation, a potentially important risk factor for late-life cognitive decline.

ObjectiveTo determine the relation between age and troponin level and its prognostic implication.DesignRetrospective cohort study.SettingFive cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC).Participants257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017.Main outcome measureAll cause mortality.Results257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient’s hospital stay. Troponin levels were standardised as a multiple of each laboratory’s 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively.ConclusionsA positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks.Study registrationClinicalTrials.gov NCT03507309.

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