Changes in biological test practices after publication of national guidelines for lipid management among patients under statin treatment

BACKGROUND: Guidelines for screening and treatment of dyslipidemia were disseminated in September and October 2000 by the National Agency of Accreditation and of Evaluation in Health (ANAES) and the French Agency of Medical Safety of the Products of Health (AFSSAPS). It was confirmed that the specific biological test was the measurement of LDL Cholestérol. OBJECTIVE: To study changes in biological test practices after diffusion of guidelines among patients on statin therapy, using Health Insurance database on reimbursement of patients living in Ile-de-France region (8,534,623 social insurance contributors). METHODS: Two groups of patients were defined in the database from the codes for medication refunds during one month (March 2000 and March 2002). The first group named "new users" included patients starting statin therapy in March, in order to follow the biological test for screening. The second group named "long term users" included patients who had been treated by statin therapy for one year or more, in order to examine the biological follow-up of treatment. All lipid biological tests were recorded during one year, before March 2000 and March 2002. Changes in medical practices were noted as the percentage of the biological tests for "exploration of a lipidic anomaly" (EAL) with determination of LDL cholesterol. RESULTS: For new users the percentage of patients having had at least one EAL for screening purposes increased by 13.5 (39.9% in 2000 and 53.4% en 2002). For long term users the change was + 21.1 (38.3% in 2000 and 59.4% in 2002) during follow-up. CONCLUSION: An improvement in biological testing practices was noted after diffusion of guidelines.     

Cholesterol lowering for secondary prevention: What statin dose should we use?

Over the past decade, 17 large placebo-controlled trials have established that statin therapy lowers LDL cholesterol and prevents cardiovascular events and death in patients with coronary disease or at high risk for atherosclerotic events. Nine trials of higher dose vs. lower dose statins (reporting data from 29,853 patients with coronary artery disease and 486 patients with other indications for statin therapy) have established that higher dose statin therapy is more efficacious than lower dose therapy in reducing myocardial infarctions/coronary death (by 16%) and stroke (by 18%) in patients with coronary disease but only reduces all-cause mortality in patients at high risk for coronary death (such as patients immediately after acute coronary syndrome). Higher dose statins are associated with statistically significantly increased risks of myopathy and elevated transaminases compared to lower dose statins; while relative risks for these outcomes are 1.2 and 4.0, the absolute increases are small (0.5% and 1%). Secondary analyses of these trials using individual patient data and multivariate adjustment will be needed to appropriately examine the incremental benefits of different LDL targets, and trials are needed to determine whether combinations of low dose statins plus other lipid lowering agents may achieve better clinical outcomes than higher dose statin therapy alone.     

Reduced Mortality Rates after Intensive Statin Therapy in Managed-Care Patients

OBJECTIVE: To evaluate whether intensive statin therapy in a managed-care setting produces greater clinical benefit than more moderate statin use. METHODS: Adults hospitalized for a coronary heart disease (CHD) event were identified from a longitudinal database of pharmaceutical and medical claims. Propensity scores representing a patient's likelihood of receiving statin therapy were calculated. Statin-treated patients were those who received statin therapy within 30 days of hospital discharge after a CHD event, had been supplied with statin therapy for at least 10 days during the follow-up period, and received statin therapy for at least 10 days before the first recurrent CHD event. Standard or intensive statin therapy was identified according to low-density lipoprotein cholesterol reductions expected with statin dose. Patients in the standard and intensive groups were matched by propensity scores to patients not receiving statin therapy after discharge. Patients in the standard statin therapy group were also matched to patients who received intensive statin therapy. Mortality rates after hospital discharge were compared in all matched groups. RESULTS: Patients treated with standard therapy experienced a 32% reduction in risk of death compared with patients not receiving statin therapy (P = 0.003). Patients who received intensive statin therapy after a CHD event experienced a 42% reduction in risk of mortality (P = 0.002) versus those not receiving statin therapy. Compared with standard therapy, intensive statin treatment further reduced the risk of death by 29% (P = 0.020). CONCLUSIONS: High risk CHD patients benefit from intensive statin therapy in a real-world, managed-care cohort, confirming the results of randomized clinical trials.     

Cholesterol measures to identify and treat individuals at risk for coronary heart disease

BACKGROUND: Low-density lipoprotein (LDL)-based guidelines are currently used to initiate and monitor cholesterol-lowering therapy. METHODS: Using stratified analyses, data from the Framingham Heart Study and the Coronary Primary Prevention Trial were evaluated to determine whether (1) cholesterol levels (total cholesterol [TC] or LDL [low-density lipoprotein]) better discriminated risk for coronary heart disease (CHD) than cholesterol ratios (LDL/HDL [high-density lipoprotein] or TC/HDL); and (2) whether changes in ratios better predicted risk reduction than changes in levels. RESULTS: Individuals with similar LDL/HDL ratios had similar risks for CHD regardless of whether they had high LDL levels or low LDL levels (23% vs 23% for the CPPT, 13.8% vs 14% for FHS men, and 8.6% vs 10.9% for FHS women). Among men with similar initial LDL/HDL ratios and similar changes in LDL/HDL ratios, risks for CHD did not differ (20.3% compared with 21.0%; p =0.96) between those with the largest and smallest reductions in LDL levels (21.3% compared with 6.5%). Among men with similar initial LDL levels and similar LDL reductions, a 20% reduction in risk for CHD was seen (19.5% compared with 24.5%; p =0.005) between those with the largest and smallest reductions in LDL/HDL ratios (23% compared with 4.6%). TC/HDL had predictive ability similar to LDL/HDL. CONCLUSIONS: Cholesterol levels do not provide incremental predictive value over cholesterol ratios in identifying people at risk for CHD. Changes in ratios are better predictors of successful CHD risk reduction than changes in levels. Future guidelines should consider incorporating ratios in initiating and monitoring successful lipid-lowering therapy.     

Switching to statins: a challenge for primary care

In 1997, doctors in England received official guidelines on the use of statins (3-hydroxy-3-methylglutaryl coenzyme A inhibitors) for primary and secondary prevention of coronary heart disease (CHD). Six months later we determined the status of patients who had been discharged from a specialist lipid clinic in 1989. 195 patients received questionnaires, with the consent of their general practitioners, regarding morbidity in, the subsequent decade and present medication, and were asked to have their cholesterol checked. Analysis was confined to the 86 with a current cholesterol measurement. Of 61 patients who had been discharged on a regimen of dietary advice and/or medication for primary prevention of CHD, 8 had been changed to a statin and 6 had been started on one. According to the new guidelines, none of these qualified for treatment. Of 25 patients who had been discharged on drugs for secondary prevention, all qualified for a statin but only 14 were receiving one--in 6 cases without achieving the recommended reductions in cholesterol. In many of the patients reviewed, treatment had not been altered to conform with the new guidelines. If hyperlipidaemic patients are to benefit promptly from advances in treatment, one solution might be a central registry that arranged regular tests and reported back to general practitioners. However, since many patients at risk do not have very high cholesterol levels, a coordinated approach to CHD risk factors would be preferable.     

Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons. OBJECTIVE: The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin. DESIGN: Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. RESULTS: LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. CONCLUSIONS: Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.     

Cholesterol,Statins, and Longevity From Age 70 to 90 Years

Background

The importance of cholesterol as a risk factor among older people, particularly among the very old, is controversial. Whether or not hypercholesterolemia warrants medical concern, and whether statins are beneficial among very old people, remain unresolved common clinical dilemmas. This study examines whether increased total cholesterol (TC) was associated with higher mortality from age 70 to 90, and if statins had a protective effect.

Methods

A representative sample (born 1920–1921) from the Jerusalem Longitudinal Cohort Study (1990–2010) was assessed at ages 70, 78, and 85 for fasting serum TC, low-density (LDL), and high-density lipoprotein (LDL); triglycerides; statin usage; social, functional, and medical domains; and all-cause mortality data (1990–2010). TC was analyzed as either continuous (10 mg/dL increments) or dichotomous variable (high TC >200 mg/dL). Cox proportional hazards models determined mortality hazard ratios (HRs), adjusting for TC, statin treatment, gender, self-rated health, smoking, hypertension, diabetes, ischemic heart disease, neoplasm, body mass index, albumin, and triglycerides.

Results

Prevalence of high TC at ages 70, 78, and 85 was 75% (n = 344), 65% (n = 332), and 34% (n = 237), and statin use was 0%, 17.9%, and 45.4%, respectively. Survival was increased (not significantly) among subjects with high TC >200 mg/dL versus ≤200 mg/dL from ages 70 to 78, 78 to 85, and 85 to 90: 79.1% versus 73.3% (log rank P = .16), 68.7% versus 61.5% (P = .10), and 73.4% versus 70.3% (P = .45), respectively. Survival was significantly increased among subjects treated with statins versus no statins at ages 78 to 85 (74.7% vs 64.3%, log rank P = .07) and 85 to 90 (76.2% vs 67.4%, P = .01). After adjustment, TC (continuous or dichotomous) was not associated with mortality from 70 to 78, 78 to 85, or 85 to 90. In contrast, statins at age 85 were associated with decreased mortality from age 85 to 90 (adjusted HR 0.61, 95% confidence interval 0.42–0.89).

Conclusions

Among older people, cholesterol levels were unrelated to mortality between the ages of 70 and 90. The protective effect of statins observed among the very old appears to be independent of TC.     

Statin Use and COVID-19 Infectivity and Severity in South Korea: Two Population-Based Nationwide Cohort Studies

BackgroundBasic studies suggest that statins as add-on therapy may benefit patients with COVID-19; however, real-world evidence of such a beneficial association is lacking.ObjectiveWe investigated differences in SARS-CoV-2 test positivity and clinical outcomes of COVID-19 (composite endpoint: admission to intensive care unit, invasive ventilation, or death) between statin users and nonusers.MethodsTwo independent population-based cohorts were analyzed, and we investigated the differences in SARS-CoV-2 test positivity and severe clinical outcomes of COVID-19, such as admission to the intensive care unit, invasive ventilation, or death, between statin users and nonusers. One group comprised an unmatched cohort of 214,207 patients who underwent SARS-CoV-2 testing from the Global Research Collaboration Project (GRCP)-COVID cohort, and the other group comprised an unmatched cohort of 74,866 patients who underwent SARS-CoV-2 testing from the National Health Insurance Service (NHIS)-COVID cohort.ResultsThe GRCP-COVID cohort with propensity score matching had 29,701 statin users and 29,701 matched nonusers. The SARS-CoV-2 test positivity rate was not associated with statin use (statin users, 2.82% [837/29,701]; nonusers, 2.65% [787/29,701]; adjusted relative risk [aRR] 0.97; 95% CI 0.88-1.07). Among patients with confirmed COVID-19 in the GRCP-COVID cohort, 804 were statin users and 1573 were matched nonusers. Statin users were associated with a decreased likelihood of severe clinical outcomes (statin users, 3.98% [32/804]; nonusers, 5.40% [85/1573]; aRR 0.62; 95% CI 0.41-0.91) and length of hospital stay (statin users, 23.8 days; nonusers, 26.3 days; adjusted mean difference –2.87; 95% CI –5.68 to –0.93) than nonusers. The results of the NHIS-COVID cohort were similar to the primary results of the GRCP-COVID cohort.ConclusionsOur findings indicate that prior statin use is related to a decreased risk of worsening clinical outcomes of COVID-19 and length of hospital stay but not to that of SARS-CoV-2 infection.     

Increased adherence to cardiac standards of care during participation in cardiac disease management programs.

Adherence to cardiovascular disease standards of care is critically important for minimizing the risk of mortality and morbidity for individuals with coronary heart disease (CHD) and heart failure (HF). The purpose of this study was to assess the ability of cardiac disease management (DM) programs to assist members with their adherence to evidence-based medicine for cardiovascular diseases. A total of 20,202 members with CHD and/or HF were evaluated 12 months prior to the start of DM programs and during their first 12 months of participation in the programs. Members were assessed for their adherence to appropriate cardiac medications. In addition, low-density lipoprotein (LDL) testing rates and clinical control of LDL values (defined as <100 mg/dL) were measured. The association between LDL control and use of lipid-lowering statins also was assessed. During participation in the cardiac programs, members achieved significant improvement in their adherence to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and beta-blockers (P < 0.0001). The cardiac population also achieved a significant increase in LDL testing rates and statin use (P < 0.0001). More members attained appropriate LDL control in year 1 compared to baseline (36% relative increase), and this improvement was associated with a 40% relative increase in statin use. In summary, participation in these cardiac DM programs assisted members to improve their adherence to cardiac medications and standards of care guidelines. Such improvements in cardiovascular disease care are likely associated with improved quality of life and reduced risk for mortality.     

联合应用依折麦布对他汀治疗冠心病患者血脂达标率的影响

目的 观察联合依折麦布对单独应用他汀类药物未能使低密度脂蛋白胆固醇(LDL-C)达标的冠心病合并糖尿病患者血脂的影响.方法 61例应用他汀治疗12周后LDL-C未达标(<2.07mmol/L)的冠心病合并糖尿病患者,在原用药基础上联合应用依折麦布(10mg/d),观察治疗8周后的血脂水平,及对丙氨酸氨基转氨酶(ALT)、天门冬氨酸氨基转氨酶(AST)及肌酸激酶(CK)的影响.结果 干预前LDL-C未达标的61例患者LDL-C分别为(2.74±0.43)nmaol/L和(2.19±0.32)mmol/L(P=0.03);干预后LDL-C水平下降20.1%(P<0.05),总胆固醇(TC)下降19.1%(P<0.05),LDL-C水平达标率为74%(45/61).干预前后甘油三酯(TG)和高密度脂蛋白胆固醇(HDL-C)无显著变化(P>0.05),AST、ALT和CK等指标也无显著变化(P>0.05).结论 联合应用依折麦布可以提高他汀类药物治疗冠心病合并糖尿病患者的LDL-C达标率,使LDL-C水平进一步降低.     

汶川地震对灾区乡村妇幼卫生信息能力的影响评估

汶川地震对灾区妇女儿童健康造成极大影响,因此必须准确获得震后妇幼健康信息,为及时干预提供依据.我国妇幼健康信息来源于妇幼卫生信息系统(MCHIS).由于MCHIS在震中受到很大程度破坏,且乡村级为MCHIS的基础部分,其信息能力决定了整个MCHIS信息产出质量.本研究通过层次分析法(AHP)评价汶川地震对乡村妇幼信息能力的影响及相对影响程度,利用聚类分析明确灾后MCHIS重建的重点区域,为灾区妇幼卫生体系重建提供决策依据.     

Combination therapy in cholesterol reduction: focus on ezetimibe and statins

Although widely used in lipid lowering therapy, HMG CoA reductase inhibitors (even when administered at high doses) are frequently insufficient to achieve guideline-recommended LDL-C goals for many patients with hypercholesterolemia in everyday clinical practice. Many patients do not achieve LDL-C goal on the initial dose of statin and the majority of these patients does not reach their goal after 6 months. As a consequence, a wide therapeutic gap exists between target LDL-C levels and those typically achieved in clinical practice. A recent and more effective therapeutic hypocholesterolemic strategy is to treat the two main sources of cholesterol simultaneously (production of cholesterol, mainly in the liver, and absorption of cholesterol in the intestine) with a complementary mechanism of action, by co-administering ezetimibe, a novel agent inhibiting cholesterol absorption, with a statin, which inhibits cholesterol production in the liver. Ezetimibe can be effectively and safely co-administered with any dose of any statin and, compared with the single inhibition of cholesterol production, afforded by statins alone, provides consistently greater reductions in LDL-C through dual inhibition of both cholesterol production and absorption. We summarize the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of using ezetimibe either alone or co-administered with statins in controlling elevated levels of plasma LDL cholesterol.     

美国狂犬病的预防策略与挑战

狂犬病是由狂犬病毒所导致的人畜共患疾病.欧美国家的狂犬病流行毒株包括犬株、蝙蝠株和浣熊株等~([1]).美国在第二次世界大战后,通过对宠物犬疫苗接种和野犬等的有效控制,人畜狂犬病的病例数显著下降.1946年,美国报告8384只病犬狂犬病和33例人狂犬病确诊病例.     

Relation of diet to cardiovascular disease risk factors in subjects with cardiovascular disease in Australia and New Zealand: analysis of the Long-Term Intervention with Pravastatin in Ischaemic Disease trial

BACKGROUND: Comparisons of the relation of diet with coronary heart disease (CHD) between countries with similar socioeconomic environments have been few. Patients in Australia and New Zealand (n = 9014) who participated in a large secondary prevention trial had significantly different CHD mortality rates. OBJECTIVE: The objective of this study was to ascertain the effects of nutrient consumption on cardiovascular disease risk in patients from the 2 countries. DESIGN: Nutrient consumption patterns were surveyed in a subgroup of 1077 patients on 3 occasions over 4 y during an intervention trial with a statin. RESULTS: Within the entire cohort of 9014 patients, the New Zealanders had significantly (40%) more cardiovascular deaths than did the Australians. In the subgroup of 1077 patients, the New Zealanders were found at entry to have eaten significantly more total (69.34 +/- 12.35 compared with 66.45 +/- 12.9 g/d) and saturated (26.23 +/- 8.41 compared with 24.37 +/- 7.36 g/d) fat (P < 0.001 for each) and to have significantly (4%) higher concentrations of LDL cholesterol (3.96 +/- 0.74 compared with 3.8 +/- 0.76 mmol/L; P < 0.001) than did the Australians. At baseline, patients with previous coronary artery bypass grafting had diets that were significantly different from those of patients without previous coronary artery bypass grafting. Relations between nutrients and plasma lipids confirmed the direct effects of saturated fatty acids on LDL cholesterol and of alcohol on plasma triacylglycerol and HDL cholesterol. Dietary counseling throughout the trial led to significant improvements in compliance with guidelines. However, neither the baseline nor the improved 1-y nutrient intakes predicted future changes in cardiovascular events. CONCLUSION: Differences in CHD mortality and in LDL-cholesterol concentrations between 2 populations with similar socioeconomic and cultural backgrounds were consistent with the amounts and types of fats eaten.     

The pivotal role of cholesterol absorption inhibitors in the management of dyslipidemia

Elevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease. Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors. It impairs the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol. Ezetimibe is an effective and safe agent for lowering LDL-C and non HDL-C. Short term clinical trials have established the role of ezetimibe monotherapy and its use in combination with statins. Furthermore, ezetimibe and statin combination therapy increased the percentage of patients who achieved their LDL-C treatment goal.