Management Of Elevated Cholesterol Research Articles

Conceptualising the experience of health risk: the case of everyday management of elevated cholesterol

Public health and individual health care are increasingly oriented towards managing risks. This ‘surveillance medicine’ does not target present illnesses but aims to prevent possible future conditions, greatly expanding the number of people implicated in medical interventions. In this paper, I interrogate the everyday experience of being at risk of illness. First, I suggest that we lack a comprehensive account of this experience, because current ways to characterise this phenomenon tend to equate risk with (chronic) illness and patient status. I then report a case study designed to avoid this starting point. I conducted interviews with laypersons with varying levels of elevated cholesterol, a common risk factor for cardiovascular diseases, who were recruited from a consumer panel in Finland in 2015. I found three elements that structure the health risk experience: the intangible nature of risk, the probabilistic character of risk estimates, and the ambivalent status of risk in terms of health and illness. While these findings overlap with previous literature in many ways, detaching health risk from illness foregrounds health management instead of patient behaviour. These findings call for caution in approaching health risk uncritically through illness categories or patient status, and I invite researchers to critically examine such elements in other cases and contexts.

World Heart Federation Cholesterol Roadmap.

The World Heart Federation has undertaken an initiative to develop a series of Roadmaps. The aim of these is to promote development of national policies and health systems approaches and identify potential roadblocks on the road to effective prevention, detection and management of cardiovascular disease (CVD) in low-and middle-income countries (LMIC), and strategies for overcoming these. This Roadmap focuses on elevated blood cholesterol, a leading risk factor for myocardial infarction, stroke, and peripheral arterial disease. Through a review of published guidelines and research papers, and consultation with a committee composed of experts in clinical management of cholesterol and health systems research in LMIC, this Roadmap identifies (1) key interventions for primordial, primary and secondary prevention of CVD through detection, treatment, and management of elevated cholesterol and familial hypercholesterolemia (FH); (2) gaps in implementation of these interventions (knowledge-practice gaps); (3)health system roadblocks to treatment of elevated cholesterol in LMIC; and (4) potential strategies for overcoming these. Despite strong evidence of the importance of cholesterol levels in primary or secondary prevention of CVD, and the effectiveness of statin therapy for cholesterol lowering and reduction of CVD risk, gaps exist in the detection, treatment, and management of high cholesterol globally. Some potential roadblocks include poor access to laboratory facilities or trained professionals for cholesterol management, low awareness of FH among the general population and health professionals, unaffordability of statins for patient households, and low awareness of the importance of persistent adherence to lipid-lowering medication. Potential solutions include point-of-care testing, provision of free or subsidized lipid-lowering medication, and treatment adherence support using text message reminders. Known effective strategies for detection, treatment, and management of elevated cholesterol and FH exist, but there are barriers to their implementation in many low-resource settings. Priorities for health system intervention should be identified at the national level, and the feasibility and effectiveness of proposed solutions should be assessed in specific contexts. Many solutions proposed in this Roadmap mayapply to other cardiovascular conditions and present opportunities for integration of CVD care in LMIC.

The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Trial: Where to Now?

The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Trial: Where to Now?

The Combination of Elevated Triglycerides and Abnormal Fasting Glucose Increases Risk of Cerebral Infarction in Patients With Mild to Moderate Hypercholesterolemia: A Post Hoc Analysis of the MEGA Study.

While triglycerides (TGs) and diabetes increase the risk of cardiovascular disease (CVD), their combined effects have not been quantified. We explored the combined effect of elevated TGs and glucose on CVD in a post hoc analysis of the large-scale Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study. In the MEGA Study, 8214 patients with mild to moderate hypercholesterolemia were randomly allocated to the diet alone group or diet plus pravastatin group and followed for 5 years. Of those, 7832 patients included in the intention-to-treat analysis were stratified into 4 groups: abnormal fasting glucose (AFG) plus high TGs, high TGs alone, AFG alone, and normal fasting glucose plus normal TGs (reference). Cox proportional hazard models were used to compare the incidence of and mortality from CVD in the 4 groups. Incidence of CVD and coronary heart disease was significantly higher in the groups with AFG alone (hazard ratio [HR], 2.02 and 3.38; P < .01, respectively) and AFG plus high TGs (HR, 2.87 and 3.87; P < .01, respectively) than the reference group. A similar relation was found in models adjusting for high-density lipoprotein cholesterol (HDL-C). Although the incidence of cerebral infarction was significantly higher only in the group with AFG plus high TGs (HR, 2.16; P = .01), it was marginally significantly higher than the reference group after adjustment for HDL-C (HR, 1.86; P = .06). Diet plus pravastatin treatment reduced the risk of cerebral infarction by 66% in the group with AFG plus high TGs (P = .03). Our findings contribute to the formulation of the hypothesis that patients with hypercholesterolemia having AFG plus high TGs have an increased risk of cerebral infarction. These are compatible with the result from the main study that patients with hypercholesterolemia randomized to diet plus pravastatin had a reduced risk of cerebral infarction.

The Effect of Low-Dose Pravastatin in Metabolic Syndrome for Primary Prevention of Cardiovascular Disease in Japan

The Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study demonstrated the beneficial effect of low-dose pravastatin treatment (10-20 mg/d) on cardiovascular disease (CVD) in Japanese patients with mild-to-moderate hypercholesterolemia. However, it is not known whether mild lipid modification is effective even for patients at high risk. In this study, we evaluated low-dose pravastatin treatment in patients with metabolic syndrome in the MEGA Study. Metabolic syndrome (MetSyn) was defined according to the modified US National Cholesterol Education Program criteria. There were 72 coronary heart disease (CHD) events and 130 CVD events in 2636 patients with MetSyn, and 70 CHD events and 125 CVD events in 5196 patients without MetSyn (hazard ratios 1.85 and 1.90, respectively). No significant risk reduction in CHD was found in the diet plus pravastatin group compared with the diet group patients with MetSyn (hazard ratio .78, P = .29). On the other hand, there was a significant 36% CVD risk reduction (P = .01) in the diet plus pravastatin group compared with the diet group patients with MetSyn, with a small number needed to treat (45). These results indicate that low-dose pravastatin provides a substantial beneficial effect for the prevention of CVD in Japanese patients with MetSyn without known CVD, a population at proportionally high risk in primary prevention.

Low-Dose Pravastatin and Age-Related Differences in Risk Factors for Cardiovascular Disease in Hypercholesterolaemic Japanese

Limited data are available regarding the relationship between age and the effect of HMG-CoA reductase inhibitor (statin) treatment. The aim of the present analysis was to evaluate the relationships between age, baseline patient characteristics, and pravastatin treatment with respect to the development of cardiovascular disease (CVD) in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study, a large-scale clinical study conducted in Japanese patients with mild or moderate hyperlipidaemia to evaluate the primary preventive effect of pravastatin against coronary heart disease. To compare the prevalence of CVD risk factors, the incidence of CVD in relation to each risk factor, and final values and changes in lipid parameters, the 7832 patients were classified into six age groups: <45, 45-49, 50-54, 55-59, 60-64 and ≥65 years. The relationship between pravastatin (10-20 mg/day) treatment efficacy and aging and the incidence of events in relation to the age groups were compared using the multivariable Cox proportional hazards model. The prevalences of diabetes mellitus and hypertension were higher in older men than in younger men, while the prevalences of smoking and obesity were higher in younger men. However, a similar difference in risk factors was not seen in women. High-density lipoprotein cholesterol was higher in women than in men across all age groups. Triglycerides were higher in younger men than in older men and all groups of women. The mean follow-up levels of total cholesterol and low-density lipoprotein cholesterol were lower in older patients than in younger patients. Pravastatin (10-20 mg/day) reduced the risk of CVD by about 30-40% across all age groups, and there was no difference between men and women. Of particular note in this analysis, CVD risk was markedly reduced in older women compared with younger women (53% vs 30% in women aged ≥65 vs ≥45 years). A similar satisfactory risk reduction for CVD was achieved with low-dose pravastatin in all men and in older women in particular, despite differences in the prevalence of risk factors. ClinicalTrials.gov Identifier: NCT00211705.

Lipid-soluble vitamin C palmitate and protection of human high-density lipoprotein from hypochlorite-mediated oxidation

transition in relation to age and weight: the study of women's health across the nation. Am J Epidemiol 2009;169:1352–61. [3] Gorodeski GI. Update on cardiovascular disease in post-menopausal women. Best Pract Res Clin Obstet Gynaecol 2002;16:329–55. [4] Kanaya AM. Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med 2002;162:1737–45. [5] Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomized controlled trial. Lancet 2006;368:1155–63. [6] Cholesterol Treatment Trialists' (CTT) CollaboratorsKearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomized trials of statins: a meta-analysis. Lancet 2008;371:117–25. [7] Mizuno K, Nakaya N, Ohashi Y, et al, MEGA Study Group. Usefulness of pravastatin in primary prevention of cardiovascular events in women: analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA study). Circulation 2008;117:494–502. [8] Tajima N, Kurata H, Nakaya N, et al, Primary Prevention Group of Adult Japanese (MEGA) Study. Pravastatin reduces the risk for cardiovascular disease in Japanese hypercholesterolemic patients with impaired fasting glucose or diabetes: diabetes subanalysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study. Atherosclerosis 2008;199:455–62. [9] Shewan LG, Coats AJ. Ethical authorship and publishing of scientific articles. Int J Cardiol 2010;144:1–2.

Pravastatin for Cardiovascular Event Primary Prevention in Patients With Mild-to-Moderate Hypertension in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study

Pravastatin for Cardiovascular Event Primary Prevention in Patients With Mild-to-Moderate Hypertension in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study

Association between Lowering Low-Density Lipoprotein Cholesterol with Pravastatin and Primary Prevention of Cardiovascular Disease in Mild to Moderate Hypercholesterolemic Japanese

To evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) change and reduction of cardiovascular disease in the Management of Elevated cholesterol in the primary prevention Group of Adult Japanese (MEGA) study. Patients in the diet plus pravastatin group were divided into tertiles by their on-treatment LDL-C level, and the hazard ratios (HRs) in each tertile were compared with the diet group at 5 years using the Cox proportional hazards model. In addition, the treatment groups were combined and divided into quintiles according to the on-treatment LDL-C level during follow-up, and the incidence of cardiovascular events was compared among the 5 groups. In the tertiles of the diet plus pravastatin group, HR was lowest in the second tertile against the diet group (HR 0.57, p=0.01) with on-treatment LDL-C range of 119.8-133.4 mg/dL. In the analysis of quintiles of the total population, a significant risk reduction of CVD was found in the fourth quintile (HR 0.48, p=0.0015) with an on-treatment LDL-C range of 120.9-133.3 mg/dL, and in the fifth quintile (HR 0.64, p=0.048) with an on-treatment LDL-C range of 56.7-120.8 mg/dL against tertile 1 with an on-treatment LDL-C range of 157.5-206.2 mg/dL. The usual Japanese dose of pravastatin therapy is sufficient in this low-risk patient population to reduce cardiovascular risk, with an achieved LDL-C level <133.4 mg/dL. Further risk reduction was not found with an achieved LDL <120 mg/dL.

Pravastatin use and cancer risk: a meta‐analysis of individual patient data from long‐term prospective controlled trials in Japan

To assess the influence of pravastatin therapy on cancer morbidity and mortality by a meta-analysis of individual patient data (IPD) from three independent Japanese large-scale clinical trials. We conducted a meta-analysis of IPD collected from three large-scale prospective studies, the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study, Kyushu Lipid Intervention Study (KLIS), and Hokuriku Lipid Coronary Heart Disease Study-Pravastatin Atherosclerosis Trial (Holicos-PAT), which compared cardiovascular outcomes with pravastatin therapy and non-statin therapy in Japanese patients with hypercholesterolemia over a follow-up period of >or=4 years. The incidence of cancer or cancer death in the pravastatin and non-statin therapy groups was compared by multivariate Cox proportional hazard models stratified by trial. Subgroup analyses by sex and age were also conducted using the same methods. In a total of 13 724 patients (mean age, 58 years; women, 48%) included in the analyses, pravastatin was not associated with an increased risk of developing cancer (hazard ratio [HR], 0.99; 95% confidence interval [95%CI], 0.81-1.19). Similarly, pravastatin therapy did not statistically affect cancer death (HR, 0.86; 95%CI, 0.61-1.21). Moreover, in subgroups analyses, no influence was observed on cancer incidence or death in relation to sex and age. Pravastatin did not increase the rate of cancer incidence or cancer death in a large population of Japanese patients followed for >70,000 patient-years.

New Cholesterol Guidelines for Children?

For children and adolescents, comprehensive guidelines for the diagnosis and management of elevated cholesterol have been published once, by the National Cholesterol Education Program in 1992.1 Since then, substantial research on early atherosclerosis and in related clinical areas has been conducted; simultaneously, the obesity epidemic has added the metabolic syndrome and its related high-triglyceride/low–high-density lipoprotein (HDL) phenotype to the agenda of those interested in establishing a consensus approach to early cardiovascular disease prevention.2 Article p 1056 Before assuming that new knowledge and secular trends in risk factors demand substantial revision of cardiovascular health guidelines for children, we must first consider several valuable, often prescient aspects of the 1992 report. First is an emphasis on the importance of nutritional management over pharmacological management of elevated low-density lipoprotein (LDL) cholesterol, unless levels clearly associated with premature cardiovascular disease exist and children are sufficiently old that advanced atherosclerotic lesions may be presumed to be present. Two randomized trials of dietary intervention, the DISC (Dietary Intervention Study in Children) and STRIP (Special Turku coronary Risk factor Intervention Project for babies) studies, have shown that the diet recommended by the 1992 report is safe and mildly effective in lowering LDL cholesterol and thus can be implemented in population-based strategies of cardiovascular disease risk lowering.3,4 Furthermore, the PDAY (Pathobiological Determinants of Atherosclerosis in Youth) study has shown that advanced, irreversible atherosclerotic lesions (American Heart Association grades IV and V) are rarely present before 19 years of age and that the relationship of risk to atherosclerosis in late adolescence is with regard to reversible early lesion grades (American Heart Association grades I through III).5 A second and woefully underrecognized virtue of the 1992 report is the definition of risk strata for LDL cholesterol, with borderline values being 110 to 129 mg/dL and high …

Treatment of Hyperlipidemia from Japanese Evidence

The treatment of hyperlipidemia is aimed at preventing cardiovascular disease (CVD) and coronary heart disease (CHD). As the incidence of CHD in Japan is about one-third lower and that of stroke is two-fold higher compared to Western countries, and the doses of lipid-lowering drugs used in foreign randomized controlled clinical trials (RCTs) are much higher than in general use in Japan, it remains unclear whether the results of RCTs conducted in Western countries could be extrapolated to Japanese patients. Recently, two major large-scale, prospective, RCTs in Japanese hypercholesterolmic patients, the Management of Elevated Cholesterol in the Primary Prevention of Adult Japanese (MEGA) study and the Japan EPA Lipid Intervention Study (JELIS), have been reported. Japanese epidemiological studies and Japanese clinical studies are reviewed. The evidence suggests that hypercholesterolemia, hypertriglyceridemia, and low HDL-cholesterol are strongly associated with increased CHD risk. Lipid-lowering medication shows beneficial effects even in low-risk populations; however, the data did not support that lower cholesterol is better. The safety and efficacy of hyperlipidemia treatment in Japanese patients are discussed.

Cholesterol-lowering drugs bring benefits to high-risk populations even when LDL is normal.

The Heart Protection Study (HPS) results were presented shortly after the National Cholesterol Education Program released the third report of clinical practice guidelines for the evaluation and management of elevated cholesterol in adults. Both the guidelines and the HPS results support an aggressive approach to managing high-risk individuals. The HPS showed that cardiovascular events and mortality were reduced in high-risk patients taking simvastatin regardless of baseline low-density lipoprotein (LDL) cholesterol levels. Some of these patients would not have met criteria for drug treatment according to the guidelines. The conclusion was that all high-risk patients with LDL > or = 100 mg/dL should be treated with drug therapy with the goal of reducing LDL to < 100 mg/dL.