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Statins may reduce cardiovascular (CV) morbidity in patients with mild-to-moderate elevations in liver enzyme levels. This post-hoc analysis of the IDEAL study compared intensive versus moderate statin therapy for the prevention of CV events in coronary heart disease patients with normal and elevated baseline levels of serum alanine aminotransferase (ALT). Cox regression analysis was used to investigate the effect of atorvastatin 80 mg/day versus simvastatin 20-40 mg/day on the risk of IDEAL study end points in patients with normal baseline ALT (defined as ALT < ULN [upper limit of normal]) versus elevated baseline ALT (ALT ≥ ULN). Of 8863 IDEAL patients with non-missing baseline ALT values, 7782 (87.8%) had an ALT < ULN and 1081 (12.2%) had an ALT ≥ ULN. In patients with elevated baseline ALT, major CV event rates were 11.5% for simvastatin and 6.5% for atorvastatin, indicating a significant risk reduction with intensive statin therapy (hazard ratio, 0.556; 95% confidence interval, 0.367-0.842; p = 0.0056). Significant heterogeneity of treatment effect was observed for major CV events, cerebrovascular events, and major coronary events, with a trend towards treatment difference for the other outcomes, indicating a greater benefit with atorvastatin in the elevated ALT group. The CV benefit of intensive lipid lowering with atorvastatin compared with a more moderate regimen with simvastatin was generally greater in patients with mildly-to-moderately elevated baseline ALT than patients with normal baseline ALT. Moderate elevations in liver enzyme levels should not present a barrier to prescribing statins, even at higher doses, in high-risk patients

The conference on “Healthy Agriculture, Healthy Nutrition, Healthy People” of the World Council on Genetics, Nutrition and Fitness for Health was held at Olympia, Greece, on October 5-8, 2010. The focus of the conference was on the evolutionary aspects of diet throughout the life cycle in terms of genetic predisposition, health, disease prevention and sedentary life styles; the dietary changes brought about my modern agriculture, agribusiness, food production systems, changes in climate and the need for urban agriculture and architecture, all of which are influenced by governments, national and international policies. Therefore, the role of governments and international organizations was extensively discussed during the last session of the conference by the participants from 20 countries representing six continents, Sağlık için Genetik, Beslenme ve Zindelikte Dünya Konseyi’nin Sağlıklı Tarım, Sağlıklı Beslenme ve Sağlıklı İnsan için Eylem Planı Açılış Konferansı 5-8 Ekim 2010 tarihinde Yunanistan’ın Olimpia şehrinde yapıldı. Konferansın odak noktası genetik yatkınlık, sağlık, hastalığın önlenmesi ve hareketsiz yaşam tarzına yaşam boyunca evrimsel bakış açısıydı. Bu evrimsel bakış, modern tarım, tarım ticareti, gıda üretim sistemleri, iklim değişiklikleri ve kentsel tarım yapılanmaları için hükümetlerce uygulanan ulusal ve uluslararası politikaların hepsini kapsamaktadır. Bundan dolayı, hükümetlerin ve uluslararası kurumların rolü, altı kıtadan 20 ülkeyi temsil eden katılımcılarla konferansın son oturumuna kadar kapsamlı olarak tartışılmıştır

Objectives This post-hoc analysis of the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial was designed to assess the comparative treatment efficacy of high-dose at ...

Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: Results from the IDEAL trial. J Intern Med 2010; 267:567-575. Objectiv ...

Background Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). Aims To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL) study database to assess the association of on-treatment lipoprotein components with prediction of HF events and to compare their predictive value with that of established risk factors such as hypertension and diabetes. Methods We used Cox regression models to study the relationships between on-treatment levels of apolipoproteins A1 and B to subsequent HF. Chi square information value from the log likelihood was used to compare the predictive value of lipoprotein components with established risk factors of HF. Findings In the IDEAL study, on-treatment apolipoproteins proved to be associated with the occurrence of new-onset HF. Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information value than that of diabetes. Calculation of the net reclassification improvement index revealed that about 3.7% of the patients had to be reclassified into more correct categories of risk once apoB/apoA-1 was added to the adjustment factors. The reduction in risk by intensive lipid-lowering treatment as compared to usual-dose simvastatin was well predicted by the difference in apoB/apoA-1 on-treatment levels. Interpretation The on-treatment ratio of apoB/apoA-1 was the strongest predictor of HF in CHD patients of both IDEAL treatment arms combined, mostly driven by the strong association with apoA-1, whereas LDL-C and non-HDL-C were less able to predict HF outcome. The predictive information value contained within apoB/apoA-1 was about 2.2 times more than that of diabetes. Between-treatment group differences in HF were to a significant extent explained by on-treatment differences in apoB/apoA-1, mostly through the changes in apoB. We argue therefore, on-treatment lipoprotein components contribute to the overall future risk of HF in statin-treated patients with CHD.

The effect of long-term β-adrenergic blockade on plasma lipids and lipoproteins was studied in 68 consecutive patients enrolled in a double-blind controlled trial of alprenolol in myocardial infarction. Thirty-three patients were treated with 200 mg alprenolol twice daily for one year, and 35 patients received placebo. Neither plasma cholesterol, plasma triglycerides nor plasma lipoproteins were significantly influenced by alprenolol.

Objectives: This study was designed to assess the relationship of high-density-lipoprotein cholesterol (HDL-C), HDL particle size, and apolipoprotein A-I (apoA-I) with the occurrence of coronary ar ...

Background: Patients at high risk of cardiovascular disease frequently fail to reach recommended low-density lipoprotein cholesterol (LDL-C) goals, partly because statin doses are not titrated to optimal effect. The ECLIPSE study was designed to compare the efficacy and safety of force-titrated treatment with rosuvastatin (10–40 mg) with that of atorvastatin (10–80 mg) in high-risk patients with hypercholesterolemia. Methods: In this 24-week, open-label, randomized, multinational, parallel-group study, 1,036 patients were randomized to rosuvastatin (n = 522) or atorvastatin (n = 514). Results: At all time points, a significantly greater percentage of patients on rosuvastatin treatment achieved the NCEP ATP III LDL-C goal of Conclusion: Rosuvastatin titrated across its recommended dose range provides a more favorable effect on lipoprotein variables than atorvastatin, enabling more high-risk patients to achieve recommended LDL-C goals.

Background Estimates of incidence are crucial to the planning of public health measures, but most studies of incidence of, for example, acute myocardial infarction (MI) are troubled by methodological problems such as; (i) selection biases of the patients being included for study, (ii) lack of identification and control of the cohort under observation, (iii) inconsistencies in the use of diagnostic criteria, and (iv) missing data. We aimed to measure directly the incidence of the entire spectrum of the acute coronary syndrome (ACS), consisting of unstable angina pectoris, MI and sudden cardiac death (SCD), by use of the new criteria for MI as proposed in 2000. Design Cohort study. Methods From a cohort of 138 290 residents of the municipality of Aarhus, Denmark, aged 30-69 years, with a demographic structure known at the individual population member level, we prospectively identified all consecutive ACS patients from 1 April 2000 to 31 March 2002. The population was identified from Danish Population Registers. Results A total of 189 victims of SCD and 457 ACS patients who survived until admission to hospital were present. Consequently, crude incidence rate of ACS was 234 per 100000 person-years. Unstable angina pectoris constituted for 16.9%, MI for 53.8% and SCD for 29.3% of ACS patients. Conclusions Crude incidence rates of ACS were 137 and 331 per 100 000 person years for women and men, respectively. The incidence rate of ACS, as measured directly, was insignificantly 6% higher than expected from Danish administrative databases. Eur J Cardiovasc Prev Rehabil 14:608-614 © 2007 The European Society of Cardiology

Contains fulltext : 50695.pdf (Publisher’s version ) (Closed access) There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B

Background —The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides ≤2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P Methods and Results —The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P Conclusions —These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients.

The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) study is an investigator-initiated trial designed to determine whether additional clinical benefit might be gained through a strategy that decreases levels of low-density lipoprotein cholesterol levels better than those currently achieved with established statin therapy in patients who have coronary heart disease. IDEAL is a multicenter prospective, randomized, open-label, blinded, end point classification study. Patients who had myocardial infarction were randomized to prescription treatment with 80 mg/day of atorvastatin or 20 mg/day of simvastatin (the dose was increased to 40 mg/day at week 24 in those patients whose plasma total cholesterol remained >5.0 mmol/L, or 190 mg/dl, or whose low-density lipoprotein cholesterol remained >3.0 mmol/L, or 115 mg/dl). The primary clinical outcome variable is the time to initial occurrence of a major coronary event, which is defined as nonfatal acute myocardial infarction, coronary death, or resuscitated cardiac arrest. The study is designed to have a power of 90% to detect a relative decrease of 20% in the atorvastatin-group compared with the simvastatin-group in the number of major events caused by coronary heart disease over approximately 5.5 years. The 8,888 randomized patients had the following characteristics: mean age 61.7 +/- 9.5 years, 19.1% women (mean age 64.0 +/- 9.5 years), baseline total cholesterol 5.1 +/- 1.0 mmol/L (197 mg/dl), low-density lipoprotein cholesterol 3.2 +/- 0.9 mmol/L (124 mg/dl), and high-density lipoprotein cholesterol 1.2 +/- 0.3 mmol/L (46 mg/dl). Drug treatment before randomization consisted of statins in 77% of patients, aspirin in 78.9%, beta blockers in 75.1%, and angiotensin-converting enzyme inhibitors in 30%

Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organisations--European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific task force. The ESC Committee for practice guidelines (CPG) supervises and coordinates the preparation of new guidelines and expert consensus documents produced by task forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements.

Major clinical end-point trials of cholesterol lowering with statins have shown consistent benefits in prevention of cardiovascular disease. Lessons from these trials include the findings that cardiovascular risk reduction is: (1) dependent on baseline cardiovascular risk; (2) dependent on magnitude of low-density lipoprotein cholesterol (LDL-C) reduction achieved with treatment; and (3) independent of initial LDL-C level. Ongoing studies will help to identify new markers of higher risk/higher treatment benefit and to define the merits of more aggressive LDL-C lowering.

Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organizations-European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilization of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific Task Force. The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements. The rationale for an active approach to the prevention of cardiovascular diseases (CVD) is …

There is considerable evidence suggesting that the current low-density lipoprotein cholesterol (LDL-C) goals to prevent coronary heart disease could be lower. This evidence includes calculations of physiological LDL-cholesterol levels and data from observational and interventional epidemiologic studies, including the Heart Protection Study. However, Heart Protection Study data can also be taken to support a strategy based on percentage reductions in LDL-C rather than a strategy of attaining absolute values of LDL-C. More effective LDL-C lowering agents, as well as combination drug therapy, will reduce LDL-C more efficiently, but it remains to be documented that such therapy is accompanied by greater reduction in risk for coronary heart disease. Moreover, even very intensive therapy will not reduce LDL-C to physiological concentrations in many patients. These considerations justify increasing emphasis on reduction in overall, multifactorial risk in individual patients at the expense of a focus on individual risk factors.

Epidemiological studies published since 1996 have established that hypertriglyceridemia can predict risk of cardiovascular disease in a manner statistically independent of HDL cholesterol. Nevertheless, the relationship of concentrations of plasma triglycerides to risk of cardiovascular disease remains less than straightforward, partly because triglycerides are carried in lipoproteins of different atherogenicity, partly because hypertriglyceridemia is associated with non-lipid atherogenic and thrombogenic processes. For example, the association of highest risk of cardiovascular disease to moderate rather than to severe hypertriglyceridemia can be understood in terms of the distribution of triglycerides between different classes of plasma lipoproteins. It is counter-intuitive to most clinicians, however, and hence it can result in the misdirection of clinical efforts including drug therapy. Fibrates lower plasma triglycerides, and raise HDL, efficiently and with few immediate side-effects. Central to their mode of action is activation of certain nuclear receptors in cells. There is no necessary connection, however, between that fascinating biochemistry and clinical benefit as defined by reductions in rates of death by coronary artery disease. A review of trials of cholesterol-lowering by diet and drugs, published between 1966 and 1996, included 12 trials of therapy with fibrates or placebo in more than 21000 patients. Overall, these trials indicated no benefit in terms of reduction in risk of coronary deaths. The period since 1996 has seen the publication of four additional trials of treatment of 6144 patients with fibrates or placebo. Two of them were major trials. The VA-HIT was very encouraging, because treatment with gemfibrozil produced a signficant reduction in the combined incidence of fatal and non-fatal coronary events. There was no significant reduction in coronary deaths, however. The results of BIP were frankly disappointing, because they demonstrated no significant effect of treatment with bezafibrate on either the primary end-point of the trial or on rates of coronary death. Clinical indications for the use of fibrates can obviously not be based on biochemical insights, however intriguing in their own right, but they have also not been satisfactorily defined by the randomized clinical trials published to date. Hope remains, however, that some clarification will result from ongoing trials of fibrate treatment of patients with type II diabetes.

The Scandinavian Simvastatin Survival Study (4S) and other randomized clinical trials have demonstrated that cholesterol-lowering treatment with statins improves prognosis in patients with coronary atherosclerosis compared with placebo. The effect of therapy with statins beyond the typical 5 to 6 years' duration of the trials, in particular regarding the risk of cancer, has not been investigated. This study examines the long-term effects of simvastatin for up to 8 years on cause-specific mortality in patients with coronary heart disease (CHD). We performed an observational, government registry-based study of mortality in the groups originally randomized to simvastatin or placebo in the 4S over an additional 2-year follow-up period, so that the median total follow-up period was 7.4 years (range 6.9 to 8.3 in surviving patients). Randomization took place at outpatient clinics at 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989. Of 4,444 patients with CHD, 2,223 and 2,221 were randomized to treatment with placebo or simvastatin therapy, respectively. Patients received treatment with simvastatin, starting at 20 mg/day, with titration to 40 mg/day at 12 or 24 weeks if total cholesterol was >5.2 mmol/L (200 mg/dl), or placebo. After the double-blind period, most patients in both treatment groups received simvastatin as open-label prescription. Of the 1,967 patients originally treated with placebo and surviving the double-blind period, 97 (4.9%) died during the following 2 years. In the group randomized to simvastatin the corresponding number was 74 of the 2, 039 survivors (3.6%). Adding these deaths to those occurring during the original trial, the total was 353 (15.9%) and 256 (11.5%) deaths in the groups originally randomized to placebo and simvastatin, respectively. The relative risk was 0.70 (95% confidence interval 0. 60 to 0.82, p = 0.00002). The total number of cancer deaths was 68 (3.1%) in the placebo group and 52 (2.3%) in the simvastatin group (relative risk 0.73, 95% confidence interval 0.51 to 0.05, p = 0. 087), and the numbers of noncardiovascular and other deaths were similar in both groups. We therefore conclude that treatment with simvastatin for up to 8 years in patients with CHD is safe and yields continued survival benefit.

Jensen JM, Gerdes LU, Jensen HK, Christiansen TM, Brorholt-Petersen JU, Faergeman O (Aarhus Amtssygehus University Hospital, Aarhus, Denmark). Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemia. J Intern Med 2000; 247: 479–484. Objectives. Existing algorithms of risk of coronary heart disease (CHD) do not pertain to patients with familial hypercholesterolaemia (FH), whose arteries have been exposed to hypercholesterolaemia since birth. We studied a cohort of FH patients to compare four diagnostic models of CHD: traditional risk factors of CHD (age, sex, cholesterol, hypertension, smoking and body mass index), cholesterol year score, and aortic as well as coronary calcium measured by spiral computed tomography (CT). Subjects. We invited 88 individuals with molecularly defined FH of whom 80 (91%) decided to participate. Results. Analysis of receiver operating characteristic curves showed that the age-adjusted coronary calcium score was more strongly associated with clinical manifestations of CHD than were traditional risk factors (P

Familial hypercholesterolemia (FH) is an autosomal inherited disorder caused by different mutations in the low density lipoprotein (LDL) receptor gene. It has been demonstrated that there is an increased risk of coronary heart disease (CHD) in heterozygous FH subjects, although this excess CHD is not only explained by the LDL-cholesterol concentration or the class of the LDL-receptor mutation. To investigate if a common polymorphism at the platelet glycoprotein (GP) IIIa gene locus could be related to CHD phenotypic variation in heterozygous FH, we have carried out a case-control study. We have studied 40 cases and 40 controls matched for age, sex and genetic defect in the LDL-receptor gene. Allele frequency of Pl A2 polymorphism for cases and controls was 20 and 22.5%, respectively, and the difference was not significant. In conclusion, our data do not support any association between the GP IIIa polymorphism and the increased prevalence of acute coronary syndromes in the heterozygous FH subjects.

This summary is taken from the Second Joint Task Force of European and other Societies Recommendations on Prevention of Coronary Heart Disease in Clinical Practice. The second Task Force was convened by the European Society of Cardiology (ESC), the European Atherosclerosis Society (EAS) and the European Society of Hypertension (ESH), the societies responsible for the original 1994 Task Force recommendations on coronary prevention (Chairman Professor K Pyorala) and consisted of a writing group, other invited members and specialists, together with representatives of other European societies and organisations as listed in the appendix. The full Task Force first met in November 1997 to review the original recommendations and agree on the principles for revision. The Writing Group then prepared a new draft of the recommendations and the specialist contributions of Professor Daan Kromhout (diet), Professor Kristina Orth-Gomer (socioeconomic, psychosocial factors and behavioural change), Professor Francois Cambi...

Aim To assess differences in treatment of ischaemic heart disease in the Scandinavian countries. Methods and Results The Scandinavian Simvastatin Survival Study (4S) lasted 5·4 years and showed that death rates in 4444 patients with coronary heart disease were 30% lower in those treated with simvastatin to lower serum cholesterol than in those given placebo. Apart from this main result, the 4S provided detailed information on rates of death and other manifestations of coronary heart disease, as well as on use of non-lipid forms of therapy. There were substantial differences in 4S placebo group rates of mortality, coronary deaths and major coronary events between countries. Surgical and medical therapy varied importantly between countries. Conclusions Major inter-country differences in rates of death and myocardial infarction in patients with coronary heart disease were likely to be due to a composite of differences in baseline characteristics including smoking. They occurred in a setting of very uneven exploitation of the potential for improving survival of patients with ischaemic heart disease.

(1998). Prevention of Coronary Heart Disease in Clinical Practice. Summary of Recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Blood Pressure: Vol. 7, No. 5-6, pp. 262-269.

Coronary heart disease (CHD) emerged in North America and Europe as a leading cause of disease and death in the mid 20th century, and is now rapidly increasing in developing nations. By the mid 1980s, American and European academic institutions had issued several sets of guidelines indicating ways to prevent CHD. Continually revised and broadly disseminated since then, CHD guidelines have become increasingly based on evidence derived from several fields of medical science including prospective clinical trials. All CHD guidelines emphasise a healthy lifestyle and the judicious use of drugs, and the focus now is on the cost of, and barriers to, the implementation of internationally adopted CHD guidelines, and on methods by which to make them acceptable and useful at national and local levels. Such methods include the development of national guidelines and the organisation of shared care programmes and healthcare teams.

Background The Scandinavian Simvastatin Survival Study (4S) demonstrated pronounced reductions in mortality and major coronary events in a cohort of patients with established coronary heart disease (CHD). The present study provides a detailed, post hoc assessment of the efficacy and safety of simvastatin therapy in the following subgroups of 4S patients: those ≥65 years of age, those Methods and Results The 4S cohort of 4444 CHD patients included 827 women and 1021 patients ≥65 years of age. Total cholesterol at baseline was 5.5 to 8.0 mmol/L with triglycerides ≤2.5 mmol/L. Patients were randomized to therapy with simvastatin 20 to 40 mg daily or placebo for a median follow-up period of 5.4 years. End points consisted of all-cause and CHD mortality, major coronary events (primarily CHD death and nonfatal myocardial infarction), other acute CHD and atherosclerotic events, hospitalizations for CHD and cardiovascular events, and coronary revascularization procedures. Mean changes in serum lipids were similar in the different subgroups. In patients ≥65 years of age in the simvastatin group, relative risks (95% confidence intervals) for clinical events were as follows: all-cause mortality, 0.66 (0.48 to 0.90); CHD mortality, 0.57 (0.39 to 0.83); major coronary events, 0.66 (0.52 to 0.84); any atherosclerosis-related event, 0.67 (0.56 to 0.81); and revascularization procedures, 0.59 (0.41 to 0.84). In women, the corresponding figures were 1.16 (0.68 to 1.99); 0.86 (0.42 to 1.74), 0.66 (0.48 to 0.91), 0.71 (0.56 to 0.91), and 0.51 (0.30 to 0.86), respectively. Conclusions Cholesterol lowering with simvastatin produced similar reductions in relative risk for major coronary events in women compared with men and in elderly (≥65 years of age) compared with younger patients. There were too few female deaths to assess the effects on mortality in women. Because mortality rates increased substantially with age, the absolute risk reduction for both all-cause and CHD mortality in simvastatin-treated subjects was approximately twice as great in the older patients.

Background: Although treatment of myocardial overload effectively reduces death from progression of heart failure, it is not known whether the retardation of progressive coronary artery disease obtained with lipid lowering treatment will prevent the onset and consequences of heart failure in patients without previous symptoms of heart failure. Methods and Results: In the Scandinavian Simvastatin Survival Study, 4444 patients with coronary heart disease without evidence of heart failure were randomized to placebo (n = 2223) or simvastatin 20–40 mg (n = 2221) and followed for more than 5 years. Among the patients who received placebo, 228 (10.3%) were diagnosed with heart failure during follow-up evaluation compared with 184 (8.3%) of patients who received simvastatin (P < .015). Mortality was 31.9% in the placebo group and 25.5% in the simvastatin group among patients who developed heart failure. These compare with 9.2 and 6.6%, respectively, among non-heart failure patients. There were 45 hospitalizations because of acute heart failure in the placebo group and 23 in the simvastatin group (NS). Patients who developed heart failure were more likely to have suffered a recurrent myocardial infarction and have a history of diabetes, peripheral artery disease, and hypertension than patients who did not develop congestive heart failure. Conclusion: Long-term prevention with simvastatin reduces the occurrence of heart failure in a cohort of patients with coronary heart disease without previous evidence of congestive heart failure.

The objective of the present study was to examine the possible associations between low molecular weight (LMW) apolipoprotein(a) (apo(a)) isoforms (F,B,S1,S2) and coronary heart disease (CHD). We conducted a nested case-control (prospective) study of five cohorts of white men: The 1936 cohort (baseline 1976, n 548) and four cohorts from MONICA I born in 1923 (n463), 1933 (n491), 1943 (n504) and 1953 (n 448) studied at baseline in 1983. At follow up in 1991, 52 subjects had developed a first myocardial infarction and 22 had been hospitalized with angina pectoris. Plasma samples obtained at baseline were stored frozen until 1993‐94, when case samples (n 74) were analyzed together with samples from matched (disease free) controls (n190). In a statistical model (conditional logistic regression) including all age groups, cholesterol (or apo B) level (PB0.01), systolic blood pressure (P0.05) and smoking (P 0.02) predicted CHD. In the statistical model Lp(a) interacted significantly with age (OR5.7; 95% CI: 1.4‐23.6; P0.016), and high Lp(a) (over 45 mg:dl) was associated with significantly increased risk in subjects under 60 years (OR3.82; 95% CI: 1.47‐9.96), but not in older men (OR 0.67; 95% CI: 0.235‐1.89). Therefore, we studied the impact of Lp(a):apo(a) and other variables in subjects who had been under 60 years when they became cases. Among the younger subjects the presence of LMW apo(a) isoforms significantly predicted the development of CHD (OR3.83; 95% CI: 1.18‐12.4). The increased risk pertained to high Lp(a) (above versus below 45 mg:dl: OR 3.68; 95% CI: 1.03‐13.10), and to Lp(a) concentrations when entered into the model as a continuous variable (P 0.04). Cholesterol or apo B (PB0.01), smoking (P0.02), systolic blood pressure (P 0.05) and low alcohol consumption (under nine drinks:week) (P0.04) were also significant predictors of CHD. We conclude that LMW apo(a) isoforms are significantly associated with increased risk of CHD in men under 60 years. © 1997 Elsevier Science Ireland Ltd.

OBJECTIVE To assess in diabetic patients with coronary heart disease (CHD) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events. RESEARCH DESIGN AND METHODS A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infarction or angina pectoris, serum total cholesterol 5.5–8.0 mmol/l, and serum triglycerides ≤ 2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S). Participants in the 4S were randomly assigned to double-blind treatment with simvastatin, 20 mg daily, with blinded dosage titration up to 40 mg daily, according to cholesterol response during the first 6–18 weeks, or placebo. Endpoints were 1) total mortality, 2) major CHD events (CHD death or nonfatal myocardial infarction), 3) other acute atherosclerotic events, 4) myocardial revascularization procedures. RESULTS Over the 5.4-year median follow-up period, simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients. The relative risks (RRs) of main endpoints in simvastatin-treated diabetic patients were as follows: total mortality 0.57 (95% CI, 0.30–1.08; P = 0.087), major CHD events 0.45 (95% CI, 0.27–0.74; P = 0.002), and any atherosclerotic event 0.63 (95% CI, 0.43–0.92; P = 0.018). The corresponding RRs in nondiabetic patients were the following: 0.71 (95% CI, 0.58–0.87; P = 0.001), 0.68 (95% CI, 0.60–0.77; P < 0.0001), and 0.74 (95% CI, 0.68–0.82; P < 0.0001). CONCLUSIONS The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD. The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events.

Background Advances in the treatment of cardiovascular disease have increased costs; annual cardiovascular healthcare expenditure in the United States currently exceeds $100 billion. Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality. Methods and Results The Scandinavian Simvastatin Survival Study is a randomized, double-blind, placebo-controlled trial in which simvastatin reduced the risk of death by 30% ( P =.0003) over the median follow-up period of 5.4 years in patients with previous myocardial infarction or stable angina pectoris as a result of a 42% reduction in the risk of coronary deaths ( P =.00001). In the present report, data prospectively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare resource use and perform a cost-minimization analysis. In the placebo group (n=2223), there were 1905 hospitalizations (average duration, 7.9 days) for acute cardiovascular events or coronary revascularization procedures among 937 patients, whereas in the simvastatin group (n=2221), there were 1403 such hospitalizations (average duration, 7.1 days) among 720 patients (all differences, P P Conclusions In addition to reducing mortality and morbidity in coronary heart disease patients, simvastatin markedly reduces use of hospital services, thus offsetting most of its cost.

INTRODUCTION The Inaugural Conference on ‘Healthy Agriculture, Healthy Nutrition, Healthy People’ of the World Council on Genetics, Nutrition and Fitness for Health was held at Ancient Olympia, Greece on October 5-8, 2010. The focus of the Conference was on the evolutionary aspects of diet throughout the life cycle in terms of genetic predisposition, health, disease prevention and sedentary lifestyles; the dietary changes brought about by modern agriculture, agribusiness, food production systems, changes in climate and the need for urban agriculture and architecture, all of which are influenced by governments, national and international policies. Therefore the role of governments and international organizations was extensively discussed during the last session of the Conference by the participants from 20 countries representing six continents.

Aims: We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how lipoprotein components related to cardiovascular disease (CVD) outcomes in these groups. Methods and results: For subjects who reached on-treatment LDL-C goals, Cox regression models were used to assess the ability of lipoprotein components to predict CVD events. Treatment with simvastatin or atorvastatin resulted in 40 per cent and 80 per cent of patients, respectively, reaching the 2.5 mmol/l goal and 12 per cent and 52 per cent, respectively, reaching the 2.0 mmol/l goal, after 1 year (all p andlt; 0.001 between groups). Adjusting for baseline LDL-C levels, hazard ratio (HR) for those reaching 2.0-2.5 mmol/l LDL-C versus those reaching andlt; 2.0 mmol/l was 1.16 (95% confidence interval [CI], 1.02-1.33, p = 0.023). An increase of the apolipoprotein B/A1 (apoB/A1) ratio by 1 standard deviation in participants who reached 2.0 mmol/l showed a HR for CVD of 1.14 (95% CI, 1.04-1.25, p = 0.004). Conclusion: More CVD patients treated with atorvastatin than simvastatin achieved either LDL-C goal and those reaching the 2.0 mmol/l goal exhibited significantly less CVD than those only reaching 2.5 mmol/l. In those reaching the 2.0 mmol/l goal, the apoB/A1 ratio still bears a relation to CVD outcome. The use of apoB/A1 ratio may provide additional predictive value to that of LDL-C.

Screening for early-stage asymptomatic cancers (e.g., breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (e.g., heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government or healthcare-sponsored reimbursement for atherosclerosis screening. Parts I and II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the vulnerable patient. These landmark discoveries, along with the new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and the treatment of the vulnerable patient are the focus of this consensus statement.

Previous studies have demonstrated that benefits of intensive statin therapy compared to standard statin therapy begin shortly after an acute event and are continued up to 2 years of follow-up. However, whether efficacy and safety of intensive statin therapy in patients with a recent cardiac event are maintained in longer-term follow-up has not been evaluated. We conducted a post hoc analysis of a subgroup of 999 patients who had a first acute myocardial infarction (MI)

Ljubica V Andersen1, Leif S Mortensen2, Jes S Lindholt3, Ole Faergeman4, Eskild W Henneberg3, Lars Frost51Department of Pharmacology, Odense University Hospital, Denmark; 2UNI-C, The Danish IT Centre for Education and Research, Aarhus, Denmark; 3Vascular Research Unit, Department of Vascular Surgery, Viborg Hospital, Denmark; 4Department of Cardiology and Internal Medicine, Aarhus University Hospital, Denmark; 5Department of Medicine, Silkeborg Hospital, DenmarkObjective: To evaluate completeness and positive predictive value of the Danish National Vascular Registry regarding registration of the surgical procedures: embolectomy of brachial, ulnar, or radial artery. Study design and settings: The study was based on first-time embolectomies in the brachial, ulnar, or radial artery performed in Denmark from January 1, 1990 to December 31, 2002. The data were primarily retrieved from the Danish National Vascular Registry and secondarily from the Danish National Registry of Patients. Medical records were retrieved using a standardized form.Results: In total, 1433 incident cases of first-time embolectomy were found in both registries. The positive predictive value of the registration was 97.5% (95% confidence interval [CI]; 96.4–98.4). The degree of completeness was 86.5% (95% CI; 84.3–88.5). For the registration period from 1990 till 1996 the degree of completeness was 78.2% (95% CI; 74.4–81.7), and from 1997 till 2002 it was 93.8% (95% CI; 91.6–95.7). Conclusion: The completeness and positive predictive value of registration of embolectomy in the upper limb in the Danish National Vascular Registry was 86.5% and 97.5%, respectively. This registry can be a valuable tool for epidemiological research and quality-monitoring. Keywords: positive predictive value, completeness, capture-recapture method, validity, embolectomy, registration.

Udgivelsesdato: 2008-Oct BACKGROUND: Cardiac rehabilitation (CR) is well documented, in randomised trials, to reduce mortality risk after myocardial infarction (MI). Selection of healthy patients for CR is a relatively unexplored problem. Our aims were to identify predictors of CR-attendance and to describe the prognosis as concerns mortality, re-admission and invasive treatment among CR-attendees as compared to CR-non-attendees. Methods: From a cohort of 138 290 persons aged 30-69 years, we identified consecutive MI patients, between 1 April 2000 and 31 March 2002. There were 206 MI patients, who survived until admission, and among the 200 who survived 30 days, 145 (72.5%) attended a comprehensive CR programme. Data were obtained from patient charts and from Danish population registers, and as a result we had no non-participation for the study. RESULTS: The 2-year mortality proportions for patients surviving the first 30 days of admission were 2.8 and 21.8% among CR-attendees and CR-non-attendees, respectively (P < 0.0001). Among CR-non-attendees, there was a smaller fraction having an invasive treatment performed as compared with CR-attendees. By multiple logistic regression controlling for age and sex, CR-attendance was associated with chest pain, whereas CR-non-attendance was associated with low gross income, single living and inverted T-wave in the electrocardiogram. CONCLUSION: CR attendance rate was 72.5%. Non-attendees have a higher mortality risk, which in part may be attributed to selection of healthy patients. Non-attendees are older and more likely to have atypical symptoms at admission, a low socioeconomic status and to live alone. Special attention is needed to improve CR attendance among such patients.

BACKGROUND: Few studies have looked into the ability of measurements of apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) or apoB/apoA-1 to predict new coronary heart disease (CHD) events in patients with CHD on statin treatment. AIMS: In the IDEAL trial, to compare lipoprotein components to predict CHD events and to what degree differences in those parameters could explain the observed outcome. METHODS: We compared the ability of treatment with atorvastatin 80 mg/day to that of simvastatin 20-40 mg/day to prevent CHD events in patients with CHD and used Cox regression models to study the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE). FINDINGS: Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors. INTERPRETATION: The on-treatment level of apoB/apoA-1 was the strongest predictor of MCE in the pooled patient population, whereas apoB and non-HDL-C were best able to explain the difference in outcome between treatment groups. Measurements of apoB and apoA-1 should be more widely available for routine clinical assessments

Thermal stress, food poisoning, infectious diseases, malnutrition, psychiatric illness as well as injury and death from floods, storms and fire are all likely to become more common as the earth warms and the climate becomes more variable. In contrast, obesity, type II diabetes and coronary artery disease do not result from climate change, but they do share causes with climate change. Burning fossil fuels, for example, is the major source of greenhouse gases, but it also makes pervasive physical inactivity possible. Similarly, modern agriculture's enormous production of livestock contributes substantially to greenhouse gas emissions, and it is the source of many of our most energy-rich foods. Physicians and societies of medical professionals have a particular responsibility, therefore, to contribute to the public discourse about climate change and what to do about it. Udgivelsesdato: 2007-Dec

BackgroundMost prognostic studies of the acute coronary syndrome (ACS) have been performed in patients selected for inclusion into clinical trials. We stratified the risk of death during the year after hospitalization for a first episode of ACS in unselected patients based on clinical and socio-economic information.MethodsIn 2000-2002 we identified 457 consecutive unselected patients admitted to hospital with a first episode of ACS. Vital status was obtained from Danish national registers.ResultsThe 1-year case-fatality proportion was 9.8%. Positive predictors of mortality were living alone, Q waves and diabetes. Negative predictors were chest pain, ST elevation and treatment with angioplasty or thrombolysis. Eur J Cardiovasc Prev Rehabil 14: 152-154 © 2007 The European Society of Cardiology

Study objective: Atherosclerosis of the coronary and other arteries is an important health problem in virtually all countries of the world, and thus there is a persisting need for the development of preventive programmes including population risk group identification. The aim of the study was to identify sociodemographic population risk indicators of an initial episode of acute coronary syndrome (ACS), including unstable angina pectoris (UAP), myocardial infarction (MI), and sudden cardiac death (SCD). Design: Cohort study of 138 290 residents of the municipality of Aarhus, Denmark, aged 30–69 years. Information on population members’ individual age, sex, social background, and eventual death was obtained from Danish Population Registers. Setting: University hospital. Patients: The study prospectively identified 646 victims of ACS from 1 April 2000 to 31 March 2002. Main results: Based on multiple logistic regression, age and single living were found to be positively associated with incident ACS in both sexes. Women >60 years living alone and men >50 years living alone were at especially high risk. They constituted only 5.4% and 7.7% of the source population, respectively, but they accounted for 34.3% and 62.4% of ACS patients dying within 30 days. Conclusions: Single living is associated with an increased risk of ACS. Thus, risk groups identified by use of information on their age and family structure may be targets for future more focused and cost effective preventive strategies. In Western populations, such high risk groups will constitute comparatively limited parts of the population, and in Denmark they are easily identifiable in routine population registers.

ObjectivePrognosis among patients admitted with possible acute coronary syndrome (ACS) may differ from that of patients with definite ACS. The aim of this study was to identify risk factors for mortality among unselected patients and to use the statistical model to identify patients at low or high mortality risk.MethodsFrom April 1, 2000, to March 31, 2002, we identified all consecutive patients aged 30 to 69 years admitted to the 2 coronary care units covering the municipality of Aarhus, Denmark (population, 138 290). ACS was considered a possible diagnosis if the physician at admission (1) had noted the presence or absence of chest pain, (2) performed a 12-lead electrocardiogram, and (3) measured markers of myocardial necrosis. In 1576 consecutive patients these criteria were fulfilled.ResultsBy logistic regression, predictors of mortality were age 60 and older, ST elevation, right bundle-branch block, arrhythmia, elevated markers of myocardial necrosis, and the diagnosis of ACS. The predictive validity of the model, as indicated by receiver operating characteristic curve area, was 85.7%, 87.8%, and 80.1% for 7-, 30-, and 365-day mortality, respectively.ConclusionsMortality may be predicted with high precision based on a statistical model. Identification of survivors by the use of a statistical model was superior as compared to simply ruling out the clinical diagnosis of ACS.

Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the "vulnerable patient." These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement. In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45-75 years of age and asymptomatic women 55-75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima-media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because10% of the population who test positive for atherosclerosis will experience a near-term event, additional risk stratification based on reliable markers of disease activity is needed and is expected to further focus the search for the vulnerable patient in the future. All individuals with asymptomatic atherosclerosis should be counseled and treated to prevent progression to overt clinical disease. The aggressiveness of the treatment should be proportional to the level of risk. Individuals with no evidence of subclinical disease may be reassured of the low risk of a future near-term event, yet encouraged to adhere to a healthy lifestyle and maintain appropriate risk factor levels. Early heart attack care education is urged for all individuals with a positive test for atherosclerosis. The SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations. Cardiovascular healthcare professionals and policymakers are urged to adopt the SHAPE proposal and its attendant cost-effectiveness as a new strategy to contain the epidemic of atherosclerotic cardiovascular disease and the rising cost of therapies associated with this epidemic.

Summary Background The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5–6-year trial periods are unknown. We extended post-trial follow-up of participants in the Scandinavian Simvastatin Survival Study (4S) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial. Methods 4S was a randomised double-blind trial of simvastatin or placebo in patients with coronary heart disease, serum total cholesterol 5·5–8·0 mmol/L, and serum triglycerides 2·5 mmol/L or lower. The double-blind period lasted for a median of 5·4 years (range for survivors 4·9–6·3) and ended in 1994. After the trial, most patients in both groups received open-label lipid-lowering treatment. National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10·4 years (range for survivors 9·9–11·3). Analysis was by intention to treat. Findings 414 patients originally allocated simvastatin and 468 assigned placebo died during the 10·4-year follow-up (relative risk 0·85 [95% CI 0·74–0·97], p=0·02), a difference largely attributable to lower coronary mortality in the simvastatin group (238 vs 300 deaths; 0·76 [0·64–0.90], p=0·0018). 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group (0·81 [0·60–1·08], p=0·14), and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group (0·88 [0·73–1·05], p=0·15). Incidence of any specific type of cancer did not rise in the simvastatin group. Interpretation Simvastatin treatment for 5 years in a placebo-controlled trial, followed by open-label statin therapy, was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only. No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group.

Aims Statins reduce LDL cholesterol (LDL-C) and the risk of vascular events, but it remains uncertain whether there is clinically relevant genetic variation in their efficacy. This study of 18 705 individuals aims to identify genetic variants related to the lipid response to simvastatin and assess their impact on vascular risk response. Methods and results A genome-wide study of the LDL-C and apolipoprotein B (ApoB) response to 40 mg simvastatin daily was performed in 3895 participants in the Heart Protection Study, and the nine strongest associations were tested in 14 810 additional participants. Selected candidate genes were also tested in up to 18 705 individuals. There was 90% power to detect differences of 2.5% in LDL-C response (e.g. 42.5 vs. 40% reduction) in the genome-wide study and of 1% in the candidate gene study. None of the associations from the genome-wide study was replicated, and nor were significant associations found for 26 of 36 candidates tested. Novel lipid response associations with variants in LPA, CELSR2/PSRC1/SORT1, and ABCC2 were found, as well as confirmatory evidence for published associations in LPA, APOE, and SLCO1B1. The largest and most significant effects were with LPA and APOE, but were only 2–3% per allele. Reductions in the risk of major vascular events during 5 years of statin therapy among 18 705 high-risk patients did not differ significantly across genotypes associated with the lipid response. Conclusions Common genetic variants do not appear to alter the lipid response to statin therapy by more than a few per cent, and there were similar large reductions in vascular risk with simvastatin irrespective of genotypes associated with the lipid response to simvastatin. Consequently, their value for informing clinical decisions related to maximizing statin efficacy appears to be limited.