Incidence Of Major Coronary Events Research Articles

Magnitude of low-density lipoprotein reduction and impact on major cardiovascular outcomes.

Magnitude of low-density lipoprotein reduction and impact on major cardiovascular outcomes.

The Impact of Radiation Dose to Heart Substructures on Major Coronary Events and Patient Survival after Chemoradiation Therapy for Esophageal Cancer.

Simple SummaryWhether it is necessary to evaluate the radiation exposure of cardiac substructures when making radiotherapy plans is one of the current research hotspots. In this cohort study of 355 patients with esophageal cancer, the radiation dose to key coronary substructures such as the left anterior descending artery V30Gy and mean left main coronary artery was closely associated with major coronary events and overall patient survival, and showed better predictive value than the mean heart dose or heart V30Gy recommended by current guidelines. Our findings suggest that, in addition to the whole heart, key coronary substructures should be contoured as organs at risk during radiotherapy plan optimization.Background: There is a paucity of data regarding the association between radiation exposure of heart substructures and the incidence of major coronary events (MCEs) in patients with esophageal cancer (ESOC) undergoing chemoradiation therapy. We studied radiation dosimetric determinants of MCE risk and measured their impact on patient prognosis using a cohort of ESOC patients treated at a single institution. Methods: Between March 2005 and October 2015, 355 ESOC patients treated with concurrent chemoradiotherapy were identified from a prospectively maintained and institutional-regulatory-board-approved clinical database. Dose-distribution parameters of the whole heart, the atria, the ventricles, the left main coronary artery, and three main coronary arteries were extracted for analysis. Results: Within a median follow-up time of 67 months, 14 patients experienced MCEs at a median of 16 months. The incidence of MCEs was significantly associated with the left anterior descending coronary artery (LAD) receiving ≥30 Gy (V30Gy) (p = 0.048). Patients receiving LAD V30Gy ≥ 10% of volume experienced a higher incidence of MCEs versus the LAD V30Gy < 10% group (p = 0.044). The relative rate of death increased with the left main coronary artery (LMA) mean dose (Gy) (p = 0.002). Furthermore, a mutual promotion effect of hyperlipidemia and RT on MCEs was observed. Conclusion: Radiation dose to coronary substructures is associated with MCEs and overall survival in patients with ESOC. In this study, the doses to these substructures appeared to be better predictors of toxicity outcomes than mean heart dose (MHD) or whole-heart V30Gy. These findings have implications for reducing coronary events through radiation therapy planning.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AimsREVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period.Methods and resultsA total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3–15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10–29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7–17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0–2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants.ConclusionThe beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms.Trial registrationInternational Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

Endovascular myocardial revascularization in patients with multivessel coronary artery disease with chronic total occlusion and high surgical risk

The main reason for incomplete myocardial revascularization is the presence of chronic coronary total occlusion (CTO), which is detected in every fourth patient during coronary angiography. At the same time, a generally accepted approach to the treatment of CTO has not yet been developed.Aim. To assess the rationale of complete myocardial revascularization in patients with multivessel coronary artery disease (CAD) with chronic total occlusion and high surgical risk.Material and methods. This retrospective, open-label, non-randomized clinical trial was carried out included 180 patients multivessel CAD and CTO. The patients underwent endovascular surgery for complete myocardial revascularization. Depending on the success of surgery, the patients were divided into groups of complete and incomplete myocardial revascularization. Endpoints were death, acute coronary syndrome, re-revascularization after 1-year follow-up. Left ventricular (LV) contractility and clinical status of patients in the study groups after 1 year of observation was assessed.Results. The median follow-up was 12,1 months. The successful rate of revascularization was 79,4%. The incidence of main composite endpoint in the group of complete myocardial revascularization was 5,59%, while in the group of incomplete revascularizations — 21,6% (p=0,005).Conclusion. The study showed that low incidence of intraoperative complications and a high successful rate of revascularization are characteristic of complete myocardial revascularization in patients at high surgical risk with multivessel CAD and CTO. Complete myocardial revascularization leads to a significant decrease in the incidence of major coronary events.

Coronary Event Analysis in Breast Cancer Patients Who Received Breast-Conserving Surgery and Post-Operative Radiotherapy: a Korean Nationwide Cohort Study.

PurposeAdjuvant breast radiotherapy (RT) following breast-conserving surgery (BCS) has been reported to induce cardiac toxicity in breast cancer patients. We investigated the incidence and risk factors of major coronary events after breast RT using Korean nationwide Health Insurance Review and Assessment data.MethodsUsing data from a nationwide quality assessment of breast cancer treatment, we identified 3,251 patients who received breast RT after BCS in 2013. Data about major coronary events were additionally collected from national claims data. We defined major coronary events according to the International Classification of Diseases, 10th revision (ICD-10) codes I20-25.ResultsA total of 172 major coronary events (5.3%) occurred among 3,251 breast cancer patients. The 1-year, 2-year, and 3-year coronary event-free survival rates were 98.1%, 96.4% and 95.2%, respectively. Patients with underlying diabetes mellitus (88.6% vs. 95.7%, p < 0.001), high blood pressure (HBP) (89.4% vs. 96.3%, p < 0.001), and cerebrovascular accident (CVA) (84.0% vs. 95.4%, p < 0.001) showed significantly worse 3-year coronary event-free survival rates than those without comorbidities. Multivariate analysis revealed that patient age (p < 0.001), HBP (p < 0.001), CVA (p = 0.025), adjuvant hormonal therapy (p = 0.034), and Herceptin therapy (p < 0.001) were significantly associated with major coronary events in breast cancer patients.ConclusionThe incidence of major coronary events after breast RT may be higher in breast-cancer patients with risk factors such as underlying HBP or CVA, or who were in receipt of adjuvant Herceptin therapy. Heart-sparing RT techniques or intensity-modulated RT should be considered for breast-cancer patients with risk factors for heart toxicity.

Stable atypical chest pain with negative anatomical or functional diagnostic test: Diagnosis no matter what or prevention at any cost?

BackgroundApproximately 1% to 2% of patients with stable atypical chest pain (SACP) experienced a major coronary event, even after a negative functional or anatomical test.MethodsOver the past 15 years, 1706 patients with SACP evaluated in our clinics underwent functional stress testing or coronary computed tomographic angiography (CTA). In these patients, we also assessed the presence of three major modifiable lifestyle‐related risk factors (cigarette smoking, low intake of fruit and vegetables, and physical inactivity). Patients were stratified according to the presence of at least one risky lifestyle factor or no risky lifestyle factors. Functional or anatomical tests were positive in 170 patients (10%). We followed the remaining 1536 patients with negative tests for 1 year to evaluate the incidence of major coronary events.ResultsThe percentage of patients reporting major coronary events was 1.2% in the group with risky lifestyles and 0.2% in the non‐risky lifestyle group (P < .01). Events were more common in smokers.ConclusionsPatients with SACP, when functional or anatomical tests are negative, have a residual risk of fatal and non‐fatal cardiovascular events of 1% at 1 year of follow‐up. People with incorrect lifestyles, especially smokers, have a higher risk of events. We think that in this population, a more effective intervention on lifestyles could be the key to reduce major cardiovascular events.

ANGPTL3 Inhibitors - Their Role in Cardiovascular Disease Through Regulation of Lipid Metabolism.

Elevated plasma lipid levels are linked to atherosclerosis, a hallmark for coronary artery disease (CAD), documented by animal studies as well as angiographic and clinical studies. The ability to treat hyperlipidemia through lifestyle changes and lipid-lowering agents has been related to the slow progression of atherosclerosis and decreased incidence of major coronary events. Angiopoietin-like proteins (ANGPTLs) are a family of secreted glycoproteins expressed in the liver that share common domain characteristics with angiopoietins, the main regulators of angiogenesis. Although ANGPTLs cannot bind the angiopoietin receptors expressed on endothelial cells, 2 ANGPTL family members (ANGPTL3 and ANGPTL4) have clinical importance because of their unambiguous effects on lipoprotein metabolism in mice and humans. The regulation of plasma lipid levels by ANGPTL3 is controlled via affecting lipoprotein lipase and endothelial lipase-mediated hydrolysis of triglycerides (TGs) and phospholipids. ANGPTL 3, along with the other 2 members, 4 and 8, is a key to balancing the distribution of circulating TGs between white adipose tissue (WAT) and oxidative tissues. Thus, ongoing trials with newly discovered medications in the form of monoclonal antibodies or antisense oligonucleotides with novel targets are under analysis and may represent a fresh frontier in the treatment of hyperlipidemia and CAD.

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BackgroundPatients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.MethodsWe conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.ResultsDuring the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of −18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.ConclusionsAmong patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192; ClinicalTrials.gov number, NCT01252953; and EudraCT number, 2010-023467-18.)

Accumulation of epicardial adipose tissue increases coronary morbidity in non-obese patients with suspected coronary artery disease

BackgroundWe explored the relationship between epicardial adipose tissue (EAT) volume, body mass index (BMI) and the incidence of major coronary events in non-obese patients with suspected coronary artery disease (CAD). MethodsWe measured EAT volume in a cohort of 722 patients who had undergone coronary computed tomography, and recorded subsequent occurrences of major coronary events (cardiac death and acute coronary syndrome), simultaneously evaluating all coronary events and all-cause death. ResultsEighteen patients experienced major coronary events: there were five cardiac deaths and 13 cases of acute coronary syndrome. BMI was inversely predictive of major coronary events (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63–0.87; p<0.001), but not for all-cause death. EAT volume predicted all coronary events (HR per 10mL, 1.11; 95% CI, 1.03–1.19; p=0.003). Although there was a trend suggestive of an inverse association with major coronary events, this was not statistically significant (HR per 10mL, 1.10; 95% CI; 1.00–1.21; p=0.059), and there was no significant relationship with all-cause death. When stratified by the first quartile (QI) of BMI (≤21.4kg/m2) and median EAT volume (107mL), the event rates in the high EAT volume and BMI QI group were significantly higher than those of other groups (adjusted HR, 5.45; 95% CI, 1.51–25.3 p=0.009, compared with the low EAT volume and BMI QI group). ConclusionOur findings suggest that suspected CAD patients with low BMI but high EAT volume are at an increased risk of major coronary events, but not all-cause death.

Eicosapentaenoic Acid (EPA) Reduces Cardiovascular Events: Relationship with the EPA/Arachidonic Acid Ratio

The clinical efficacy of fish oil and high-purity eicosapentaenoic acid ethyl ester (hp-EPA-E) for treating cardiovascular disease (CVD) has been reported. Fish oil contains saturated and monounsaturated fatty acids that have pharmacological effects opposite to those of ω3 fatty acids (ω3). Moreover, ω3, such as EPA and docosahexaenoic acid (DHA), do not necessarily have the same metabolic and biological actions. This has obscured the clinical efficacy of ω3. Recently, the Japan EPA Lipid Intervention Study (JELIS) of hp-EPA-E established the clinical efficacy of EPA for CVD, and higher levels of blood EPA, not DHA, were found to be associated with a lower incidence of major coronary events. A significant reduction in the risk of coronary events was observed when the ratio of EPA to arachidonic acid (AA) (EPA/AA) was > 0.75. Furthermore, the ratio of prostaglandin (PG) I3 and PGI2 to thromboxane A2 (TXA2) ([PGI2 + PGI3]/TXA2) was determined to have a linear relationship with the EPA/AA ratio as follows: (PGI2 + PGI3)/TXA2 =λ + π＊ (EPA/AA). Like PGI2, PGI3 not only inhibits platelet aggregation and vasoconstriction, but also is assumed to reduce cardiac ischemic injury and arteriosclerosis and promote angiogenesis. Thus, the effects of EPA in reducing the risk of CVD could be mediated by biological action of PGI3 in addition to hypotriglyceridemic action of EPA. Compared with DHA, EPA administration increases the EPA/AA ratio and the (PGI2 + PGI3)/TXA2 balance to a state that inhibits the onset and/or progression of CVD.

Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia

OBJECTIVEIt has recently been highlighted that proinflammatory (M1) macrophages predominate over anti-inflammatory (M2) macrophages in obesity, thereby contributing to obesity-induced adipose inflammation and insulin resistance. A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA) reduces the incidence of major coronary events. In this study, we examined the effect of EPA on M1/M2-like phenotypes of peripheral blood monocytes in obese dyslipidemic patients.RESEARCH DESIGN AND METHODSPeripheral blood monocytes were prepared from 26 obese patients without and 90 obese patients with dyslipidemia. Of the latter 90 obese patients with dyslipidemia, 82 patients were treated with or without EPA treatment (1.8 g daily) for 3 months.RESULTSMonocytes in obese patients with dyslipidemia showed a significantly lower expression of interleukin-10 (IL-10), an M2 marker, than those without dyslipidemia. EPA significantly increased serum IL-10 and EPA levels, the EPA/arachidonic acid (AA) ratio, and monocyte IL-10 expression and decreased the pulse wave velocity (PWV), an index of arterial stiffness, compared with the control group. After EPA treatment, the serum EPA/AA ratio was significantly correlated with monocyte IL-10 expression. Only increases in monocyte IL-10 expression and serum adiponectin were independent determinants of a decreased PWV by EPA. Furthermore, EPA significantly increased the expression and secretion of IL-10 in human monocytic THP-1 cells through a peroxisome proliferator–activated receptor (PPAR)γ-dependent pathway.CONCLUSIONSThis study is the first to show that EPA increases the monocyte IL-10 expression in parallel with decrease of arterial stiffness, which may contribute to the antiatherogenic effect of EPA in obese dyslipidemic patients.

The case for more intensive use of statins.

The case for more intensive use of statins.

Statin adherence and the risk of major coronary events in patients with diabetes: a nested case-control study.

To evaluate whether good statin adherence is associated with a reduced incidence of major coronary events (MCEs) among diabetic patients with and without coronary heart disease (CHD). Using data derived by linkage of nationwide health databases in Finland, we conducted a nested case-control analysis of 3513 cases with an MCE, a composite of acute myocardial infarction and/or coronary revascularization, and 20,090 matched controls identified from a cohort of 60,677 statin initiators with diabetes. Cases and controls were matched according to gender, time of cohort entry and duration of follow-up and further classified to two risk groups according to the presence of CHD at statin initiation. The incidence of MCEs was compared between patients with good statin adherence (the proportion of days covered ≥80%) and patients with poor statin adherence (<80%). Odds ratios (OR) for MCEs were estimated by conditional logistic regression adjusting for several covariables. Good statin adherence was associated with a reduced incidence of MCEs in those with prior CHD [OR 0.84 (95% CI 0.74-0.95)] and in those without it [OR 0.86 (95% CI 0.78-0.95)]. The association persisted among those followed up for 5 years or longer [OR 0.77 (95% CI 0.58-1.02) and OR 0.79 (95% CI 0.66-0.94) respectively]. In sensitivity analyses, a reduced MCE incidence was observed also in those without any documented cardiovascular disease (CVD) at statin initiation [OR 0.87 (95% CI 0.78-0.96) overall and OR 0.80 (95% CI 0.66-0.97) for those followed up 5 years or longer]. In patients with diabetes, good adherence to statins predicts reduced incidence of MCEs irrespective of the presence of CHD at statin initiation.

A Systematic Review on the Short-term Efficacy and Safety of Nicorandil for Stable Angina Pectoris in Comparison with Those of β-Blockers, Nitrates and Calcium Antagonists

Nicorandil significantly reducted the incidence of major coronary events in patients with stable angina in a long-term trial, although there are few reports on its short-term efficacy in the treatment and prevention of angina symptoms. We performed a meta-analysis of the short-term efficacy of nicorandil compared with antianginal drugs for stable angina. We selected 20 reports (vs. β-blockers, n=6; vs. nitrates, n=6; vs. calcium antagonists, n=8) of prospective controlled trials from MEDLINE, the Cochrane Library, and Japana Centra Revuo Medicina. The trials were short in duration (median 5 weeks). We combined the results using odds ratios (OR) for discrete data and weighted mean differences (WMD) for continuous data. Compared with antianginal drugs, nicorandil did not show significant reduction of angina episodes per week (vs. β-blockers, -1.50 [95% confidence interval (CI): -4.09, 1.09]; vs. nitrates, 0.22 [95% CI: -1.22, 1.65]; vs. calcium antagonists, -0.23 [95% CI: -1.37, 0.90]). Furthermore, there were no significant differences in time to ischemia (total exercise duration, time to 1-mm ST depression, time to onset of pain). Although the total numbers of adverse events with each antianginal drug were similar, heart rate and blood pressure were significantly decreased by calcium antagonists but not changed by nicorandil (8.09 [95% CI: 3.20, 12.98] and 8.64 [95% CI: 3.28, 13.99], respectively). Thus this study suggests that short-term therapy with nicorandil is as effective as standard therapy and that nicorandil can also be used as a first-line agent in patients with stable angina.

Preventive Effects of Eicosapentaenoic Acid on Coronary Artery Disease in Patients With Peripheral Artery Disease - Subanalysis of the JELIS Trial -

The JELIS trial examined the preventive effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemia. Previous investigators have reported that patients with peripheral artery disease (PAD) have a poor prognosis due to the potential risk for CAD. We conducted a subanalysis to examine whether the incidence of CAD was high in patients with PAD and whether EPA prevented the occurrence of CAD. Of 18,645 the Japan EPA lipid intervention study (JELIS) patients, 223 had PAD (control group; complicated (n=77), newly diagnosed (n=29), EPA group; complicated (n=96), newly diagnosed (n=21)). We analyzed the incidence of major coronary events (MCE) in the 2 groups. Cox proportional hazard ratio adjusted for baseline risk factor levels was used to test differences between the 2 groups. The incidence of MCE in the control group was significantly higher in patients complicated with PAD and in those newly diagnosed with PAD than in patients without PAD (complicated: hazard ratio 1.97, P=0.039; newly diagnosed: hazard ratio 2.88, P=0.030). As for patients with PAD, the EPA group had a significantly lower MCE hazard ratio than the control group (hazard ratio 0.44, 95% confidence interval 0.19-0.97, P=0.041). Subanalysis of the JELIS trial demonstrated that in patients with PAD the incidence of CAD was higher than in controls, and that EPA markedly reduced the occurrence of CAD in those patients.

Incremental Effects of Eicosapentaenoic Acid on Cardiovascular Events in Statin-Treated Patients With Coronary Artery Disease Secondary Prevention Analysis From JELIS

Results from JELIS (Japan EPA Lipid Intervention Study) demonstrated the efficacy of pure eicosapentaenoic acid (EPA) in preventing coronary artery disease (CAD) in hypercholesterolemic patients under statin treatment. The present study examined in detail whether EPA is effective for the secondary prevention of CAD. Patients with established CAD and a total cholesterol level > or =250 mg/dl were observed with a mean follow-up of 4.6 years. They were randomly assigned to receive either 1,800 mg of EPA + statin (EPA group) or statin alone (control group). The incidence of major coronary events (MCE) were compared in the 2 groups. The incidence of MCE was significantly lower in the EPA group (8.7% vs 10.7%, adjusted hazard ratio =0.77, 95% confidence interval (CI) 0.63-0.96, P=0.017, number needed to treat (NNT) =49). Among 1,050 patients with prior myocardial infarction (MI), the incidence of MCE in the EPA group (15.0%) was significantly lower than that in the control group (20.1%, adjusted hazard ratio =0.73, 95%CI 0.54-0.98, P=0.033, NNT =19). EPA is effective for secondary prevention of CAD, especially in individuals with prior MI, and should be added to conventional treatment.

In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid

A large-scale, prospective, randomized clinical trial has recently revealed that the addition of highly purified eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduces the incidence of major coronary events. Here we investigated in vivo and in vitro effect of EPA on monocyte adhesion to endothelial cells and adhesion molecules. A new en face immunohistochemistry of endothelial surface in combination with confocal microscopy revealed marked reduction of lipopolysaccharide (LPS)-induced monocyte adhesion to the aortic endothelium in parallel with the suppression of vascular cell adhesion molecule 1 (VCAM-1) and nuclear translocation of nuclear factor-kappaB p65 in EPA-treated mice relative to vehicle-treated groups. In an in vitro adhesion assay system under physiological flow conditions, EPA inhibited LPS-induced monocyte adhesion and endothelial adhesion molecules. We found significant decrease in plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and sVCAM-1 in patients with the metabolic syndrome after a 3-month administration of highly purified EPA (1.8 g daily). Multivariate regression analysis revealed that EPA administration is the only independent determinant of sICAM-1 and sVCAM-1. This study provides evidence that EPA inhibits monocyte adhesion to endothelial cells in parallel with the suppression of endothelial adhesion molecules in vivo and in vitro.

Rosuvastatin: The Most Efficient Treatment Option For Patients With Dyslipidemia

It has been unequivocally proven that lowering serum cholesterol reduces the risk of cardiovascular disease. For every 1% reduction in serum total cholesterol, the risk of coronary heart disease is lowered by 2%, and with a 1 mmol/l reduction in low-density lipoprotein cholesterol (LDL-C), the 5-year incidence of major coronary events, coronary revascularization and stroke, is reduced by approximately one fifth. The risk of cardiovascular disease increases linearly with increasing serum cholesterol. Thus, people with high cholesterol levels have the highest risk, but in any population the largest number of cardiovascular events and deaths will occur in people whose serum cholesterol is only marginally elevated, as they form the largest pool of the background population. Unfortunately, a significant number of patients requiring lipid-modifying therapy remain untreated or suboptimally treated, with almost half failing to reach current guideline targets for LDL-C, and therefore remaining at unacceptably high risk of a cardiovascular event, such as a myocardial infarction or stroke, despite receiving medical treatment. This is partly due to noncompliance or ineffective use of cholesterol-lowering therapy. Consequently, there remains a need for an effective, well-tolerated agent or combination of such agents that can produce beneficial changes in the atherogenic lipid profile and enable the majority of patients requiring lipid-lowering therapy to reach their recommended LDL-C goals. Among the statins, rosuvastatin monotherapy has been shown to have superior efficacy in reducing LDL-C across its licensed dose range. At daily doses of 5–40 mg, rosuvastatin produces mean reductions in plasma LDL-C of 45–63%, achieves LDL-C goals in 48–89% of patients, and is more effective than equivalent and maximum doses of atorvastatin, simvastatin and pravastatin. This means that fewer patients treated with rosuvastatin will require other cholesterol-lowering agents, leading to lower treatment cost. Rosuvastatin also improves high-density lipoprotein cholesterol (HDL-C), triglyceride and lipid ratios, such as LDL-C:HDL-C ratio. Furthermore, a recent study showed that significant regression of atherosclerosis can be achieved with intensive statin therapy using rosuvastatin 40 mg. The safety and tolerability of rosuvastatin is similar to other marketed statins. Rosuvastatin as a single therapy is a valuable option and, thus far, the most efficient treatment for a broad spectrum of patients with dyslipidemia. In particular, the overall lipid profile, including HDL-C and triglycerides, in patients with Type 2 diabetes or the metabolic syndrome is markedly improved with rosuvastatin therapy.

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins

Results of previous randomised trials have shown that interventions that lower LDL cholesterol concentrations can significantly reduce the incidence of coronary heart disease (CHD) and other major vascular events in a wide range of individuals. But each separate trial has limited power to assess particular outcomes or particular categories of participant. A prospective meta-analysis of data from 90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol. During a mean of 5 years, there were 8186 deaths, 14,348 individuals had major vascular events, and 5103 developed cancer. Mean LDL cholesterol differences at 1 year ranged from 0.35 mmol/L to 1.77 mmol/L (mean 1.09) in these trials. There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0.88, 95% CI 0.84-0.91; p<0.0001). This reflected a 19% reduction in coronary mortality (0.81, 0.76-0.85; p<0.0001), and non-significant reductions in non-coronary vascular mortality (0.93, 0.83-1.03; p=0.2) and non-vascular mortality (0.95, 0.90-1.01; p=0.1). There were corresponding reductions in myocardial infarction or coronary death (0.77, 0.74-0.80; p<0.0001), in the need for coronary revascularisation (0.76, 0.73-0.80; p<0.0001), in fatal or non-fatal stroke (0.83, 0.78-0.88; p<0.0001), and, combining these, of 21% in any such major vascular event (0.79, 0.77-0.81; p<0.0001). The proportional reduction in major vascular events differed significantly (p<0.0001) according to the absolute reduction in LDL cholesterol achieved, but not otherwise. These benefits were significant within the first year, but were greater in subsequent years. Taking all years together, the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 (95% CI 39-57) fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 (19-31) per 1000 among participants with no such history. There was no evidence that statins increased the incidence of cancer overall (1.00, 0.95-1.06; p=0.9) or at any particular site. Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individual's absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event.

Metabolic syndrome criteria: ready for clinical prime time or work in progress?The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

This editorial refers to ‘Impact of statins in microalbuminuric subjects with the metabolic syndrome: a substudy of the PREVEND Intervention Trial’† by C.A. Geluk et al. , on page 1314 Geluk et al. 1 describe a subgroup analysis of the PREVEND trial in which they tested whether pravastatin reduced risk for major adverse cardiac events in micro-albuminuric patients with and without the metabolic syndrome defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria.2 Although pravastatin did not reduce incidence of adverse cardiac events in the total cohort,3 an impressive 60% relative risk reduction was noted in the subgroup with both micro-albuminuria and metabolic syndrome [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.17–0.89], whereas micro-albuminuric individuals without metabolic syndrome did not appear to benefit. The higher event rate in the former group concurs with other evidence indicating a more ‘malignant’ outcome when micro-albuminuria accompanies other risk factors (e.g. endothelial dysfunction4) than when it occurs in isolation. The investigators suggested that their study supports the use of statins in micro-albuminuric subjects with metabolic syndrome to reduce incidence of major coronary events. So what does this mean for clinicians in practice? Should we advocate that metabolic syndrome status be recorded in all micro-albuminuric patients, and that differential treatment with statins of micro-albuminuric patients with and without metabolic syndrome become routine practice? To address these issues, several aspects of the currently reported findings would benefit from further comment. First, the total number of cardiac events in this study numbered <50, relatively modest compared with major statin trials. Therefore, one explanation for lack of apparent statin benefit in subjects with micro-albuminuria but without … *Corresponding author. Tel: +44 141 211 4312; fax: +44 141 553 2558. E-mail address : nsattar{at}clinmed.gla.ac.uk