ObjectiveTo assess low-density lipoprotein cholesterol (LDL-C) response in patients after initiation of statins, and future risk of cardiovascular disease (CVD).MethodsProspective cohort study of 165 411 primary care patients, from the UK Clinical Practice Research Datalink, who were free of CVD before statin initiation, and had at least one pre-treatment LDL-C within 12 months before, and one post-treatment LDL-C within 24 months after, statin initiation. Based on current national guidelines, <40% reduction in baseline LDL-C within 24 months was classified as a sub-optimal statin response. Cox proportional regression and competing-risks survival regression models were used to determine adjusted hazard ratios (HRs) and sub-HRs for incident CVD outcomes for LDL-C response to statins.Results84 609 (51.2%) patients had a sub-optimal LDL-C response to initiated statin therapy within 24 months. During 1 077 299 person-years of follow-up (median follow-up 6.2 years), there were 22 798 CVD events (12 142 in sub-optimal responders and 10 656 in optimal responders). In sub-optimal responders, compared with optimal responders, the HR for incident CVD was 1.17 (95% CI 1.13 to 1.20) and 1.22 (95% CI 1.19 to 1.25) after adjusting for age and baseline untreated LDL-C. Considering competing risks resulted in lower but similar sub-HRs for both unadjusted (1.13, 95% CI 1.10 to 1.16) and adjusted (1.19, 95% CI 1.16 to 1.23) cumulative incidence function of CVD.ConclusionsOptimal lowering of LDL-C is not achieved within 2 years in over half of patients in the general population initiated on statin therapy, and these patients will experience significantly increased risk of future CVD.

Summary Background The vast majority of individuals with familial hypercholesterolaemia in the general population remain unidentified worldwide. Recognising patients most likely to have the condition, to enable targeted specialist assessment and treatment, could prevent major coronary morbidity and mortality. We aimed to evaluate a clinical case-finding algorithm, the familial hypercholesterolaemia case ascertainment tool (FAMCAT), and compare it with currently recommended methods for detection of familial hypercholesterolaemia in primary care. Methods In this external validation study, FAMCAT regression equations were applied to a retrospective cohort of patients aged 16 years or older with cholesterol assessed, who were randomly selected from 1500 primary care practices across the UK contributing to the QResearch database. In the main analysis, we assessed the ability of FAMCAT to detect familial hypercholesterolaemia (ie, its discrimination) and compared it with that of other established clinical case-finding approaches recommended internationally (Simon Broome, Dutch Lipid Clinic Network, Make Early Diagnosis to Prevent Early Deaths [MEDPED] and cholesterol concentrations higher than the 99th percentile of the general population in the UK). We assessed discrimination by area under the receiver operating curve (AUROC; ranging from 0·5, indicating pure chance, to 1, indicating perfect discrimination). Using a probability threshold of more than 1 in 500 (prevalence of familial hypercholesterolaemia), we also assessed sensitivity, specificity, positive predictive values, and negative predictive values in the main analysis. Findings A sample of 750 000 patients who registered in 1500 UK primary care practices that contribute anonymised data to the QResearch database between Jan 1, 1999, and Sept 1, 2017, was randomly selected, of which 747 000 patients were assessed. FAMCAT showed a high degree of discrimination (AUROC 0·832, 95% CI 0·820–0·845), which was higher than that of Simon Broome criteria (0·694, 0·681–0·703), Dutch Lipid Clinic Network criteria (0·724, 0·710–0·738), MEDPED criteria (0·624, 0·609–0·638), and screening cholesterol concentrations higher than the 99th percentile (0·581, 0·570–0·591). Using a 1 in 500 probability threshold, FAMCAT achieved a sensitivity of 84% (1028 predicted vs 1219 observed cases) and specificity of 60% (443 949 predicted vs 745 781 observed non-cases), with a corresponding positive predictive value of 0·84% and a negative predictive value of 99·2%. Interpretation FAMCAT identifies familial hypercholesterolaemia with greater accuracy than currently recommended approaches and could be considered for clinical case finding of patients with the highest likelihood of having hypercholesterolaemia in primary care. Funding UK National Institute for Health Research School for Primary Care...

Background and Purpose: Data about variations in stroke incidence and subsequent major adverse outcomes are essential to inform secondary prevention and prioritizing resources to those at the greatest risk of major adverse end points. We aimed to describe the age, sex, and socioeconomic differences in the rates of first nonfatal stroke and subsequent major adverse outcomes. Methods: The cohort study used linked Clinical Practice Research Datalink and Hospital Episode Statistics data from the United Kingdom. The incidence rate (IR) ratio of first nonfatal stroke and subsequent major adverse outcomes (composite major adverse cardiovascular events, recurrent stroke, cardiovascular disease-related, and all-cause mortality) were calculated and presented by year, sex, age group, and socioeconomic status based on an individual’s location of residence, in adults with incident nonfatal stroke diagnosis between 1998 and 2017. Results: A total of 82 774 first nonfatal stroke events were recorded in either primary care or hospital data—an IR of 109.20 per 100 000 person-years (95% CI, 108.46–109.95). Incidence was significantly higher in women compared with men (IR ratio, 1.13 [95% CI, 1.12–1.15]; P <0.001). Rates adjusted for age and sex were higher in the lowest compared with the highest socioeconomic status group (IR ratio, 1.10 [95% CI, 1.08–1.13]; P <0.001). For subsequent major adverse outcomes, the overall incidence for major adverse cardiovascular event was 38.05 per 100 person-years (95% CI, 37.71–38.39) with a slightly higher incidence in women compared with men (38.42 versus 37.62; IR ratio, 1.02 [95% CI, 1.00–1.04]; P =0.0229). Age and socioeconomic status largely accounted for the observed higher incidence of adverse outcomes in women. Conclusions: In the United Kingdom, incidence of initial stroke and subsequent major adverse outcomes are higher in women, older populations, and people living in socially deprived areas.

Background Although obesity is a well-recognised risk factor for cardiovascular disease (CVD), the impact of long-term body mass index (BMI) changes in overweight or obese adults, on the risk of heart failure, CVD and mortality has not been quantified. Methods This population-based cohort study used routine UK primary care electronic health data linked to secondary care and death-registry records. We identified adults who were overweight or obese, free from CVD and who had repeated BMI measures. Using group-based trajectory modelling, we examined the BMI trajectories of these individuals and then determined incidence rates of CVD, heart failure and mortality associated with the different trajectories. Cox-proportional hazards regression determined hazards ratios for incident outcomes. Results 264,230 individuals (mean age 49.5 years (SD 12.7) and mean BMI 33.8 kg/m2 (SD 6.1)) were followed-up for a median duration of 10.9 years. Four BMI trajectories were identified, corresponding at baseline, with World Health Organisation BMI classifications for overweight, class-1, class-2 and class-3 obesity respectively. In all four groups, there was a small, stable upwards trajectory in BMI (mean BMI increase of 1.06 kg/m2 (± 3.8)). Compared with overweight individuals, class-3 obese individuals had hazards ratios (HR) of 3.26 (95% CI 2.98–3.57) for heart failure, HR of 2.72 (2.58–2.87) for all-cause mortality and HR of 3.31 (2.84–3.86) for CVD-related mortality, after adjusting for baseline demographic and cardiovascular risk factors. Conclusion The majority of adults who are overweight or obese retain their degree of overweight or obesity over the long term. Individuals with stable severe obesity experience the worst heart failure, CVD and mortality outcomes. These findings highlight the high cardiovascular toll exacted by continuing failure to tackle obesity.

ObjectiveTo assess the incidence of hip fracture and all major osteoporotic fractures (MOF) in patients with chronic obstructive pulmonary disease (COPD) compared with non-COPD patients and to evaluate the use and performance of fracture risk prediction tools in patients with COPD. To assess the prevalence and incidence of osteoporosis.DesignPopulation-based cohort study.SettingUK General Practice health records from The Health Improvement Network database.ParticipantsPatients with an incident COPD diagnosis from 2004 to 2015 and non-COPD patients matched by age, sex and general practice were studied.OutcomesIncidence of fracture (hip alone and all MOF); accuracy of fracture risk prediction tools in COPD; and prevalence and incidence of coded osteoporosis.MethodsCox proportional hazards models were used to assess the incidence rates of osteoporosis, hip fracture and MOF (hip, proximal humerus, forearm and clinical vertebral fractures). The discriminatory accuracies (area under the receiver operating characteristic [ROC] curve) of fracture risk prediction tools (FRAX and QFracture) in COPD were assessed.ResultsPatients with COPD (n=80 874) were at an increased risk of fracture (both hip alone and all MOF) compared with non-COPD patients (n=308 999), but this was largely mediated through oral corticosteroid use, body mass index and smoking. Retrospectively calculated ROC values for MOF in COPD were as follows: FRAX: 71.4% (95% CI 70.6% to 72.2%), QFracture: 61.4% (95% CI 60.5% to 62.3%) and for hip fracture alone, both 76.1% (95% CI 74.9% to 77.2%). Prevalence of coded osteoporosis was greater for patients (5.7%) compared with non-COPD patients (3.9%), p<0.001. The incidence of osteoporosis was increased in patients with COPD (n=73 084) compared with non-COPD patients (n=264 544) (adjusted hazard ratio, 1.13, 95% CI 1.05 to 1.22).ConclusionPatients with COPD are at an increased risk of fractures and osteoporosis. Despite this, there is no systematic assessment of fracture risk in clinical practice. Fracture risk tools identify those at high risk of fracture in patients with COPD.