AimsTo appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).Methods and resultsWe assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects.ConclusionConsistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.

Introduction Patients with coronary heart disease (CHD) are at high cardiovascular risk, and controlling risk factors in this population is especially important to prevent CHD morbidity and mortality. SURF CHD (Survey of Risk factors in Coronary Heart Disease) II is a clinical audit on secondary prevention of CHD. The goals are to simplify and assess the recording and management of cardiovascular risk factors in patients with CHD. Methods SURF CHD II consists in a brief online survey conducted during routine outpatient visits in patients with a previous acute coronary syndrome (ACS), stable angina, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Information is collected electronically on demographics, risk factor history (smoking history, physical activity), risk factor measurements (blood pressure, BMI, waist circumference), laboratory values and medication. Risk factor targets were defined as follows: no prior smoking or having stopped smoking, practice of at least 30 minutes of moderate physical activity 3–5 times per week, BMI <25 kg/m2, waist circumference <94 cm in men and <80 cm in women, blood pressure of <140/90 mmHg (<140/85 mmHg in diabetics), LDL <70 mg/dL, HDL >40 mg/dL in men and >45 mg/dl in women, triglycerides <150 mg/dL, and HbA1c <7% in diabetic participants. Results 12884 patients from 32 countries participated in SURF CHD in 5 regions: 10195 in Europe, 2048 in South-East Asia (SEA), 415 in the Americas, 210 in North Africa-Eastern Mediterranean (NAEM), and 13 in Western Pacific. All centres participating were located in urban areas and 81.6% were public Women represented 24.6% of the participants, mean age 64.1 years (sd 11.2 years). 57.7% of the patients had a previous PCI, 50% ACS, 29.5% stable angina and 16.1% CAGB. The percentage of risk factor recording and target attainment by region is presented in Table 1. Risk factor recording ranged from 26.8% (waist circumference) to 94.3% for blood pressure. Target attainment varied from 25.8% with a BMI <25 kg/m2, to 76.3% of participants that had never smoked or had stopped smoking. The South East Asian region presented the highest percentages of risk factor target attainment for smoking, physical activity, BMI, waist circumference and LDL. 92.% of participants used antiplatelet medication, 100% antihypertensive medication and 89.4% lipid-lowering medications. Conclusion Risk factor recording was reasonable, but poor for some risk factors such as waist circumference and Hba1c. In line with earlier clinical audits, there is still substantial room for improvement in risk factor control in this high cardiovascular risk population. There were regional variations, with the highest level of attainment for most risk factors targets in South East Asia. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): SURF II is conducted within the framework of the ESC Prevention of CVD Programme, led by the European Association of Preventive Cardiology (EAPC).