Marginal role for 53 common genetic variants in cardiovascular disease prediction.

OBJECTIVE: We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype-based risk score was assessed. METHODS: Data were from seven prospective studies including 11 851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10 years' follow-up. We calculated a score from 53 CVD-related single nucleotide polymorphisms and an established CVD risk equation 'QRISK-2' comprising phenotypic measures. The area under the receiver operating characteristic curve (AUROC), detection rate for given false-positive rate (FPR) and net reclassification improvement (NRI) index were estimated for gene scores alone and in addition to the QRISK-2 CVD risk score. We also evaluated use of genetic information only for those at intermediate risk according to QRISK-2. RESULTS: The AUROC was 0.635 for QRISK-2 alone and 0.623 with addition of the gene score. The detection rate for 5% FPR improved from 11.9% to 12.0% when the gene score was added. For a 10-year CVD risk cut-off point of 10%, the NRI was 0.25% when the gene score was added to QRISK-2. Applying the genetic risk score only to those with QRISK-2 risk of 10%-<20% and prescribing statins where risk exceeded 20% suggested that genetic information could prevent one additional event for every 462 people screened. CONCLUSION: The gene score produced minimal incremental population-wide utility over phenotypic risk prediction of CVD. Tailored prediction using genetic information for those at intermediate risk may have clinical utility

A study in high-risk, maximally pretreated patients to determine the potential use of PCSK9 inhibitors at various thresholds of total and LDL cholesterol levels

PURPOSE OF THE STUDY: Statins and ezetimibe reduce low-density lipoprotein cholesterol (LDL-c) and cardiovascular disease (CVD) risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-c by 50%-70% and might be useful in refractory patients. The National Institute for Health and Care Excellence (NICE) technology appraisal guidance (TAG) recommends use of these drugs in secondary prevention and familial hypercholesterolaemia (FH) at differing LDL-c thresholds. We have estimated the proportion of patients in whom this third-line drug might be useful. STUDY DESIGN: We used data from a lipid-lowering audit programme to study 72 with FH and/or CVD of 271 patients referred over 12 months who failed to achieve target total cholesterol (TC) and LDL-c levels. All 72 patients were treated with ezetimibe, and 69 cases also received statins. We used LDL-c thresholds 1.5-5.5 mmol/L to estimate how many of these refractory patients could benefit from PCSK9 inhibitors. RESULTS: In 72 patients, TC and LDL-c targets were not met by 64 and 53 patients, respectively. We judged using the NICE TAG that only one patient (1.4% ezetimibe requiring and 0.4% total referrals) required a PCSK9 inhibitor. CONCLUSIONS: We determined that the proportion of patients eligible for a PCSK9 inhibitor at various TC and LDL-c levels is modest. This may reflect the use of all available statins in UK lipid clinics often at non-daily frequency. We suggest that cost-effective use of PCSK9 inhibitors requires prescribing being restricted to clinicians working in specialised lipid clinics

Lifestyle advice and interventions for cardiovascular risk reduction: A systematic review of guidelines.

BACKGROUND: Lifestyle factors are important in preventing cardiovascular disease (CVD) development. We aimed to systematically review guidelines on primary prevention of CVD and their recommendations on lifestyle advice or intervention, in order to guide primary prevention programs. METHODS: Publications in MEDLINE, CINAHL over 7 years since May 3, 2009 were identified. G-I-N International Guideline Library, National Guidelines Clearinghouse, National Library for Health Guideline finder, Canadian Medical Association InfoBase were searched. On the February 8, 2017, we updated the search from Websites of organizations responsible for guidelines development. STUDY SELECTION: 2 reviewers screened the titles and abstracts to identify Guidelines from Western countries containing recommendations for lifestyle advice and interventions in primary prevention of CVD. DATA EXTRACTION: 2 reviewers independently assessed rigor of guideline development using the AGREEII instrument, and one extracted recommendations. RESULTS: Of the 7 guidelines identified, 6 showed good rigor of development (range 45-86%). The guidelines were consistent in recommendations for smoking cessation, limiting saturated fat and salt intake, avoiding transaturated-fat and sugar, with particular emphasis on sugar-sweetened beverages. Guidelines generally agreed on recommendations for physical activity levels and diets rich in fruit, vegetables, fish and wholegrains. Guidelines differed on recommendations for specific dietary patterns and alcohol consumption. Recommendations on psychological factors and sleep are currently limited. CONCLUSIONS: Current guidelines agree on the importance of lifestyle in the prevention of CVD with consensus on most factors including physical activity, smoking cessation and diet, which should be actively integrated in cardiovascular risk reduction programs aiming to improve clinical outcomes.Barts Charity for the HAPPY (Heart Attack Prevention Programme for You) London study (grant number 437/1412)

Obesity

Obesity is a risk factor for hypertension, high blood lipids, type 2 diabetes, myocardial infarction and stroke. Adipocytes expand in a state of energy excess which can lead to inflammation, insulin resistance and increasing cardiovascular risk. As even modest weight loss occurs, adipose cell size reduces reversing the adverse cardiometabolic changes seen in obesity. Weight loss can be induced through low calorie diets and bariatric surgery, resulting in improvements in cardiovascular risk factors such as blood pressure, lipids and inflammatory markers and reducing the need for current and future cardiovascular medications