World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide.</p

A systematic review of population-based studies on Lipid profiles in Latin America and the Caribbean

We aimed to study time trends and levels of mean total cholesterol and lipid fractions, and dyslipidaemias prevalence in Latin America and the Caribbean (LAC).Systematic-review and meta-analysis of population-based studies in which lipid (total cholesterol [TC; 86 studies;168,553 people], HDL-Cholesterol [HDL-C; 84 studies;121,282 people], LDL-Cholesterol [LDL-C; 61 studies;86,854 people], and triglycerides [TG;84 studies;121,009 people]) levels and prevalences were laboratory-based. We used Scopus, LILACS, Embase, Medline and Global Health; studies were from 1964-2016. Pooled means and prevalences were estimated for lipid biomarkers from ≥2005.The pooled means(mg/dl) were 193for TC, 120 for LDL-C, 47 for HDL-C, and 139 for TG; no strong trends. The pooled prevalence estimates were 21% for high TC, 20% for high LDL-C, 48% for low HDL-C, and 21% for high TG; no strong trends. These results may help strengthen programs fordyslipidaemias prevention/management in LAC

Pleiotropic actions of factor Xa inhibition in cardiovascular prevention: mechanistic insights and implications for anti-thrombotic treatment

Atherosclerosis is a chronic inflammatory disease in which atherothrombotic complications lead to cardiovascular morbidity and mortality. At advanced stages, myocardial infarction, ischemic stroke and peripheral artery disease (PAD), including major adverse limb events (MALE), are caused either by acute occlusive atherothrombosis, or by thromboembolism. Endothelial dysfunction, vascular smooth muscle cell activation and vascular inflammation are essential in the development of acute cardiovascular events. Effects of the coagulation system on vascular biology extend beyond thrombosis. Under physiological conditions, coagulation proteases in blood are pivotal in maintaining hemostasis and vascular integrity. Under pathological conditions, including atherosclerosis, the same coagulation proteases (including factor Xa, factor VIIa and thrombin) become drivers of atherothrombosis, working in concert with platelets and vessel wall components. While initially atherothrombosis was attributed primarily to platelets, recent advances indicate the critical role of fibrin clot and plasma coagulation factors. Mechanisms of atherothrombosis and hypercoagulability vary depending on plaque erosion or plaque rupture. In addition to contributing to thrombus formation, factor Xa and thrombin can affect endothelial dysfunction, oxidative stress, vascular smooth muscle cell function as well as immune cell activation and vascular inflammation. By these mechanisms they promote atherosclerosis and contribute to plaque instability. In this review, we first discuss the postulated vasoprotective mechanisms of protease activated receptor (PARs) signaling induced by coagulation enzymes under physiological conditions. Next, we discuss preclinical studies linking coagulation with endothelial cell dysfunction, thromboinflammation and atherogenesis. Understanding these mechanisms is pivotal for the introduction of novel strategies in cardiovascular prevention and therapy. We therefore translate these findings to clinical studies of direct oral anticoagulant (DOAC) drugs and discuss the potential relevance of dual pathway inhibition for atherothrombosis prevention and vascular protection