Relationship between low-density lipoprotein cholesterol,lipid-lowering agents and risk of stroke: a meta-analysis of observational studies (n = 355,591) and randomized controlled trials (n = 165,988)

IntroductionThe impact of low-density lipoprotein cholesterol (LDL-C) on the risk of different types of strokes is unclear. Therefore, we systematically evaluated the impact of LDL-C levels (cohort studies) and lipid-lowering agents (LLAs) (randomized controlled trials) on the different types of stroke.Material and methodsPubMed, SCOPUS, Web of Science and Google Scholar were searched up to 1^st September 2019. The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis. The leave-one-out method was performed as sensitivity analysis. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 35% reduction in outcomes after administration of LLAs.ResultsParticipants in the highest category of LDL-C had a lower risk of hemorrhagic stroke (RR = 0.91, 95% CI: 0.85–0.98, I² = 0%) compared with the lowest category of LDL-C. Subjects with the highest category of LDL-C had a higher risk of ischemic stroke (RR = 1.11, 95% CI: 1.07–1.14, I² = 0%) compared to the lowest LDL-C category. LLAs decreased the risk of all types of strokes for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.88, 95% CI: 0.80–0.96, absolute risk reduction (ARR): 0.7%, number needed to treat (NNT): 143, I² = 53%, n = 13). Statin therapy decreased the risk of all strokes (RR = 0.88, 95% CI: 0.80–0.97, ARR = 0.6%, NNT = 167, I² = 56%). With regard to ischemic stroke only, LLAs decreased the risk of ischemic stroke for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.75, 95% CI: 0.67–0.83, ARR = 1.3%, NNT = 77, I² = 0%); the same was observed for statins (RR = 0.76, 95% CI: 0.69–0.84, ARR = 1.3%, NNT = 77, I² = 32%). TSA indicated that both benefit boundaries and optimal sample size were reached. There was no significant effect of LLAs regardless of the achieved level of LDL-C on the risk of hemorrhagic stroke; however, TSA indicated that further studies are needed to settle the question and most of the effects were subject to high levels of heterogeneity.ConclusionsOur study sheds light on the debatable association between low LDL-C and different type of strokes. This information can help determine the optimal LDL-C range for stroke prevention, and help plan future LLA studies.     

Low triglyceride levels affect calculation of low-density lipoprotein cholesterol values

The Friedewald formula for the calculation of low-density lipoprotein cholesterol (LDL-C) values is fairly accurate provided the triglyceride value is less than 400 mg/dL. It is not clear whether the estimation is also valid in the presence of low triglyceride and high cholesterol levels. We describe herein a patient with a low triglyceride value of approximately 50 mg/dL, a high cholesterol level, and a discrepant LDL-C level. The LDL-C level using the Friedewald calculation turned out to be much higher than the LDL-C level using direct measurement. We, therefore, suggest that in the presence of low triglyceride and high cholesterol levels, the LDL-C level should be measured directly instead of using the Friedewald calculation.     

Lipid measurements in the management of cardiovascular diseases: Practical recommendations a scientific statement from the national lipid association writing group

Lipoprotein measurements are pivotal in the management of patients at risk for atherosclerotic coronary heart disease (CHD) with myocardial infarction and coronary death as the main outcomes, and for atherosclerotic cardiovascular disease (ASCVD), which includes CHD and stroke. Recent developments and changes in guidelines affect optimization of using lipid measures as cardiovascular biomarkers. This scientific statement reviews the pre-analytical, analytical, post-analytical, and clinical aspects of lipoprotein measurements. Highlights include the following: i) It is acceptable to screen with nonfasting lipids. ii) non-high-density lipoprotein HDL-cholesterol (non-HDL-C) is measured reliably in either the fasting or the nonfasting state and can effectively guide ASCVD prevention. iii) low density lipoprotein cholesterol (LDL-C) can be estimated from total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) measurements. For patients with LDL-C>100 mg/dL and TG ≤150 mg/dL it is reasonable to use the Friedewald formula. However, for those with TG 150-400 mg/dL the Friedewald formula for LDL-C estimation is less accurate. The Martin/Hopkins method is recommended for LDL-C estimation throughout the range of LDL-C levels and up to TG levels of 399 mg/dL. For TG levels ≥400 mg/dL LDL-C estimating equations are currently not recommended and newer methods are being evaluated. iv) When LDL-C or TG screening results are abnormal the clinician should consider obtaining fasting lipids. v) Advanced lipoprotein tests using apolipoprotein B (apoB), LDL Particle Number (LDL-P) or remnant cholesterol may help to guide therapeutic decisions in select patients, but data are limited for patients already on lipid lowering therapy with low LDL-C levels. Better harmonization of advanced lipid measurement methods is needed. Lipid measurements are recommended 4-12 weeks after a change in lipid treatment. Lipid laboratory reports should denote desirable values and specifically identify extremely elevated LDL-C levels (≥190 mg/dL at any age or ≥160 mg/dL in children) as severe hypercholesterolemia. Potentially actionable abnormal lipid test results, including fasting triglycerides (TG) ≥500 mg/dL, should be reported as hypertriglyceridemia. Appropriate use and reporting of lipid tests should improve their utility in the management of persons at high risk for ASCVD events.     

The acute effect of 30 min of moderate exercise on high density lipoprotein cholesterol in untrained middle-aged men

Summary Fifteen middle-aged, untrained (defined as no regular exercise) men (mean age 49.9 years, range 42–67) cycled on a cycle ergometer at 50 rpm for 30 min at an intensity producing 60% predicted maximum heart rate [(f _c,max), wheref _{c, max} = 220 - age]. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (Tg) concentrations were measured from fasting fingertip capillary blood samples collected at rest, after 15 and 30 min of exercise, and at 15 min post-exercise. The mean HDL-C level increased significantly from the resting level of 0.85 mmol · l^–1 to 0.97 mmol · 1^–1 (P<0.05) after 15 min of exercise, increased further to 1.08 mmol · 1^–1 (P<0.01) after 30 min of exercise and remained elevated at 1.07 mmol · 1^–1 (P<0.01) at 15 min post-exercise. These increases represented changes above the mean resting level of 14.1%, 27.1% and 25.9% respectively. The HDL-C/LDL-C ratio increased significantly from a resting ratio of 0.20 to 0.26 after 30 min of exercise (P < 0.01) and to 0.24 at 15 min post-exercise (P<0.05). The mean Tg level increased significantly from a resting level of 0.88 mmol · 1^–1 to 1.05 mmol · 1^–1 after 15 min, and to 1.06 mmol · I^–1 after 30 min of exercise (P<0.05 at each time). The TC/HDL-C ratio decreased significantly (P=0.05) after 30 min of exercise and at 15 min post-exercise by 18.8% and 14%, respectively. No significant changes were observed in the levels of TC or LDL-C over time. These results indicate that 30 min of moderate exercise elicits significant changes in HDL-C concentration during and up to 15 min after the exercise in untrained middle-aged men with low mean resting levels of HDL-C (0.85 mmol · 1^–1).     

Beta-blocker induced changes in the cholesterol: High-density lipoprotein cholesterol ratio and risk of coronary heart disease

Summary The lowering of blood pressure with beta-blocking drugs has had a low impact on coronary heart disease (CHD) mortality and the question has been raised whether adverse changes in plasma lipoproteins offset the benefits of blood pressure reduction. Comparison of plasma lipoprotein concentrations in hypertensive patients treated with commonly used beta-blockers with lipoprotein concentrations in patients with coronary heart disease shows that these drugs cause clinically important shifts in the cholesterol ratio [total cholesterol (TC): high-density lipoprotein cholesterol (HDLC)] and reductions in the atheroprotective lipoprotein HDLC. The magnitude of these changes is sufficient to increase the risk of heart attack two- to four-fold depending on the initial cholesterol ratio and the duration of treatment. Only beta-blockers with marked intrinsic sympathomimetic agonist activity (pindolol) or combined alpha-beta-blocking properties (Labetalol) appear free of adverse effects on plasma lipoproteins and triglycerides. Chronic treatment with other betablockers should be accompanied by cholesterol and HDLC measurements at the beginning of therapy. Plasma lipoprotein measurements at 3–6 month intervals seem mandatory in patients with cholesterol values greater than 6 mmol/l (230 mg/dl) and (TC):HDLC ratios above 5 at the start of treatment. The risk of a coronary event must be regarded as unacceptable when the cholesterol ratio exceeds a critical value of about 6. Further controlled studies are needed to evaluate the effects of beta-blockers in hypertension when administered for periods of up to a year or more. More information is required on the behaviour of lipoprotein subspecies and apoproteins. Since the changes in lipoproteins reported in studies referred to in this review may have been submaximal the risks and the benefits from beta-blocker therapy must be carefully considered.     

Long-term experience with extracorporeal low-density lipoprotein cholesterol removal by dextran sulfate cellulose adsorption

Summary Patients with familial hypercholesterolemia have a high incidence of coronary heart disease due to diet- and drug-resistant, elevated low-density lipoprotein cholesterol (LDL-C). Five patients with familial hypercholesterolemia and diet- and drug-resistant LDL-C > 230 mg/dl were treated by LDL apheresis using dextran sulfate cellulose adsorption (Liposorber System LA-15, Kaneka). Plasma separation was by 0.5-m² polysulfone hollow fiber filter. Two columns containing 150 ml of dextran sulfate cellulose alternately adsorbed LDL and were regenerated by 4.1% saline. The five patients received a total of 360 treatments at 7-day intervals. The treated plasma volume per session was 4.1 ± 0.41. Postapheresis values compared with preapheresis were: total cholesterol, 40%; LDL-C, 28%; VLDL-C, 65%; HDL-C, 95%; triglycerides, 70%; white blood cells, 116%; platelets, 87%; C3 complement, 79%; fibrinogen, 64%; albumin, 94%. The decrease in HDL-C per treatment was not significant. The safety parameters showed only slight changes. The initial LDL of 436 ± 172 mg/dl decreased to mean pre-apheresis levels of between 150 and 100 mg/dl. The anti-atherogenic HDL increased in three and remained unchanged in two patients. Adverse events like hypotension, angina pectoris, and technical problems occurred in 11 of the 360 treatments. Long-term treatment of patients with diet- and drug-resistant familial hypercholesterolemia by extracorporeal dextran sulfate cellulose adsorption is effective and safe.Abbreviations LDL low-density lipoprotein - LDL-C lowdensity lipoprotein cholesterol - VLDL very low-density lipoprotein - HDL high-density lipoprotein - HDL-C high-density lipoprotein cholesterol - CHD coronary heart disease - FH familial hypercholesterolemia - HMG CoA hydroxy-3methyl-glutaryl coenzyme A - PTT partial thromboplastin time - IU international units - ANOVA analysis of variance     

Treatment adherence and effect of concurrent statin intensity on the efficacy and safety of alirocumab in a real-life setting: results from ODYSSEY APPRISE

IntroductionThe phase IIIb open-label ODYSSEY APPRISE study prospectively assessed the safety and efficacy of alirocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in a real-life setting in high cardiovascular risk patients with heterozygous familial hypercholesterolemia or low-density lipoprotein cholesterol (LDL-C) not at goal despite maximally tolerated dose statins ± other lipid-lowering therapies ({"type":"clinical-trial","attrs":{"text":"NCT02476006","term_id":"NCT02476006"}}NCT02476006). This post-hoc analysis assessed patient adherence to statins and alirocumab, plus alirocumab efficacy and safety, according to concomitant statin intensity and prior ezetimibe usage.Material and methodsPatients received alirocumab 75 or 150 mg (dose adjustment based on physician’s judgment) every 2 weeks (for ≥ 3 to ≤ 30 months).ResultsOf 994 enrolled and treated patients, 58.4% received concomitant high-intensity statins, 18.2% received moderate/low-intensity statins, and 23.4% received no statin; 55.9% received prior ezetimibe. Mean alirocumab adherence (percent adherence defined as injections received/theoretical injections × 100) was 96.6% over 72.4 weeks’ mean treatment duration. Mean LDL-C reduction from baseline at Week 12 was similar between statin intensity subgroups (53.6–55.7%). More patients achieved LDL-C < 1.8 mmol/l and/or ≥ 50% reduction from baseline in the ≥ 100% versus < 100% adherent to alirocumab subgroup; high-intensity and low/moderate-intensity subgroups versus no statin subgroup; and prior ezetimibe versus no prior ezetimibe subgroup. Treatment-emergent adverse events occurred in 65.2–75.1% and 68.0–76.3% of patients across statin and ezetimibe subgroups, respectively.ConclusionsIn a real-life setting, patient adherence to alirocumab was high. Alirocumab provided clinically significant reductions in LDL-C, with most patients achieving LDL-C treatment targets across background statin therapy and prior ezetimibe therapy subgroups.     

Effectiveness and tolerability of ezetimibe co-administered with statins versus statin dose-doubling in high-risk patients with persistent hyperlipidemia: The EZE(STAT)2 trial

Introduction

When a standard dose of statins fails to achieve lipid control in patients at high risk for coronary artery disease (CAD), increasing the statin dosage or co-administration of additional agents is recommended. The aim of this study was to compare the safety and lipid-lowering efficacy of doubling the standard statin dose (STAT2) to that of co-administering ezetimibe 10 mg/day (EZE+statin) in Canadian patients at high CAD risk with persistent hyperlipidemia upon statin treatment.

Material and methods

Six-week, open-label, randomized, multicentre study. The primary outcome was the change in plasma LDL-C and secondary measures included the change in additional lipid parameters. Safety was assessed with the incidence of emergent adverse events (AEs).

Results

Eight hundred eighty-five patients (EZE+statin, n=586; STAT2, n=299) completed the study. The mean (SD) percent change in low-density lipoprotein cholesterol (LDL-C) was – 30.9% (18.2) for the EZE+statin group and –18.4% (19.0) for the STAT2 group (p=0.001). Percent and absolute decreases in total cholesterol (TC), triglycerides and the TC to high-density lipoprotein cholesterol ratio (TC/HDL-C) were significantly greater for the EZE+statin group (p = 0.001). After 6 weeks of treatment, 70% of the patients in the EZE+statin group and 48% of patients in the STAT2 group (OR=2.45, p<0.001) achieved target LDL-C levels of<2.5 mmol/l. Incidence of AEs was similar between groups, with the exception of a higher incidence of muscle disorders in the STAT2 group.

Conclusions

In patients at high CAD risk who are above the LDL-C target while on statin monotherapy, co-administration of ezetimibe is well tolerated and more effective in improving the lipid profile compared to doubling the existing statin dose.     

Genome-wide haplotypic testing in a Finnish cohort identifies a novel association with low-density lipoprotein cholesterol

We performed genome-wide tests for association between haplotype clusters and each of 9 metabolic traits in a cohort of 5402 Northern Finnish individuals genotyped for 330 000 single-nucleotide polymorphisms. The metabolic traits were body mass index, C-reactive protein, diastolic blood pressure, glucose, high-density lipoprotein (HDL), insulin, low-density lipoprotein (LDL), systolic blood pressure, and triglycerides. Haplotype clusters were determined using Beagle. There were LDL-associated clusters in the chromosome 4q13.3-q21.1 region containing the albumin (ALB) and platelet factor 4 (PF4) genes. This region has not been associated with LDL in previous genome-wide association studies. The most significant haplotype cluster in this region was associated with 0.488 mmol/l higher LDL (95% CI: 0.361–0.615 mmol/l, P-value: 6.4 × 10⁻¹⁴). We also observed three previously reported associations: Chromosome 16q13 with HDL, chromosome 1p32.3-p32.2 with LDL and chromosome 19q13.31-q13.32 with LDL. The chromosome 1 and chromosome 4 LDL associations do not reach genome-wide significance in single-marker analyses of these data, illustrating the power of haplotypic association testing.     

Associations between the lipid profile and the development of hypertension in young individuals – the preliminary study

IntroductionHypertension is the leading direct cause of death in the world and one of the most important risk factors for cardiovascular disease (CVD). Elevated blood pressure (BP) often coexists with lipid disorders and is an additional factor that increases CV risk. Nowadays, we are able to distinguish low density lipoproteins (LDL) and high density lipoproteins (HDL) subfractions. Except LDL also HDL small subfractions can increase the risk of CV events. Therefore, we aimed to investigate the associations between changes of lipoprotein subfractions and the risk of hypertension development.Material and methodsIn 2-year long study 200 volunteers with normal blood pressure at the age of 19–32 years were included. Each volunteer underwent detailed medical examination, 12-lead electrocardiogram was taken at rest, echocardiogram, lipid subfraction assessment (using Lipoprint^®) and two 24-hour BP measurements.ResultsMean total cholesterol concentration was 189 mg/dl (4.89 mmol/l), with mean LDL concentration of 107 mg/dl (2.77 mmol/l), HDL of 63 mg/dl (1.63 mmo/l), very low-density lipoprotein (VLDL) of 40 mg/dl (1.04 mmol/l) and triglycerides (TG) of 89 mg/dl (1.00 mmol/l). Subfractions LDL 1–3 were most abundant, LDL 4–5 making up a marginal portion and LDL 6–7 were not observed. Whereas, subfractions HDL 4–6 were most abundant, in lower concentration was present HDL 1–3 and HDL 8–10. We showed that increased systolic blood pressure coreclated significantly with HDL cholesterol concentrations (p = 0.0078), HDL intermediate subgractions (p = 0.0451), with HDL-3 subfraction (p = 0.0229), and intermediate density lipoprotein-A (IDL-A) (p = 0.038). A significant correlation between increased diastolic blood pressure and HDL lipoprotein levels (p = 0.0454) was only observed.ConclusionsObtained results indicating correlation between total HDL levels and HDL-3 subfraction concentration (for systolic BP) and the tendency to develop hypertension.Key words: hypertension, high density lipoproteins, low density lipoproteins, lipid profile, lipoprotein subfractions     

The lipoprotein profile of women with hyperprolactinaemic amenorrhoea

The aim of this study was to evaluate the lipoprotein profile in women with hyperprolactinaemic amenorrhoea and to establish whether effective dopamine agonist therapy might have a beneficial effect. Blood samples were collected from women with hyperprolactinaemic amenorrhoea and from controls matched for age, body mass index and smoking. Follow-up blood samples were collected from women on dopamine agonist therapy as treatment for their hyperprolactinaemia. Plasma cholesterol, high density lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein cholesterol, triglycerides, serum oestradiol and prolactin were measured. No statistically significant differences were found in the lipoprotein profile of the patient (n = 15) and control (n = 15) groups. During treatment with the dopamine agonist, bromocriptine (n = 9), significant reduction in total cholesterol [4.87 (3.98-5.87) versus 5.60 (4.55-6.61) mmol/l, P = 0.024] and LDL cholesterol [3.22 (2.01-4.23) versus 3.72 (2.59-4.93) mmol/l, P = 0.033] was noted. We conclude that beneficial alterations in the lipoprotein profile may occur in response to effective dopamine agonist therapy, presumably as a consequence of return of ovarian function and alleviation of oestrogen deficiency. Women with hyperprolactinaemic amenorrhoea should be encouraged to take effective therapy to improve their lipoprotein profile and potentially reduce their cardiovascular risk.     

The blood lipid regulation of Monascus-produced monascin and ankaflavin via the suppression of low-density lipoprotein cholesterol assembly and stimulation of apolipoprotein A1 expression in the liver

Background/Purposes

Monascin (MS) and ankaflavin (AK) produced by Monascus purpureus NTU 568 were proven to show excellent hypolipidemic effects in our previous studies; however, the mechanism is still unclear.

Multicenter evaluation of four homogenous LDL-cholesterol assays

International guidelines emphasize the importance of LDL cholesterol (LDL-C) assay in the care and follow-up of patients with cardiovascular risk. Most studies and common practice use Friedewald's formula for LDL-C calculation. The accuracy of the result depends closely on the precision of the input parameters (total cholesterol, triglycerides (TG) and HDL cholesterol), and discrepancies between calculated LDL-C and measurement by reference methods appear when TG exceed 4.5 mmol/L, or in the presence of abnormal lipoproteins. These restrictions and uncertainties in calculations have prompted the recent development of direct and homogeneous methods that fit all analyzers. A multicenter evaluation of four direct assays of LDL-C (Daiichi, Denka Seiken, Kyowa, Wako) was carried out on 45 serum samples (TG below 3.1 mmol/L) in eight laboratories using different analyzers. For three methods (Daiichi, Kyowa, Wako), the interlaboratory reproducibility was markedly improved relative to that of calculation. A strong correlation was found for all new methods when compared with a beta-quantification assay. Average bias in Denka Seiken assays was greater than Kyowa's and Daiichi's (although less dispersed for the latter) and for Wako all bias were positive. The relationship between bias variations and the lipid parameters of the samples was studied. Three methods, Daiichi, Kyowa and Wako, revealed a significant positive correlation between bias and serum VLDL-C/TG ratio, clearly indicating that cholesterol enrichment of VLDL was a source of variability in these assays. Specificity of the four methods was tested in situation of dyslipidemia by spiking isolated lipoproteins (chylomicrons, VLDL and HDL). This experiment revealed differences in behavior, most evidently upon addition of VLDL. No method was truly specific, but up to 8 mmol/L of TG the variations were acceptable. In the presence of type III hyperlipoproteinemia, however, only the Denka Seiken method was reliable. Linearity up to 20 mmol/L (Daiichi, Denka Seiken) or 14 mmol/L (Kyowa, Wako) of LDL-C allows these tests to be used in main routine cases. New direct assays are an obvious technological advance in terms of analytical performance and conveniency. Their use for the diagnosis and follow-up of hyperlipidemic patients offers an alternative that overcomes the limitations of the Friedewald calculation.     

Serum pro-oxidant-antioxidant balance and low-density lipoprotein oxidation in healthy subjects with different cholesterol levels

Abstract. In this study, we investigated serum pro-oxidantantioxidant balance in 210 healthy subjects divided into groups with low and high atherogenic risk according to the levels of serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein- cholesterol (HDL-C). Diene conjugate (DC), malondialdehyde (MDA), polyunsaturated fatty acid (PUFA), vitamin E, and vitamin C levels and antioxidant activity (AOA) were determined in the serum. Endogenous DC and copperinduced MDA levels were also measured in the LDL fraction isolated by precipitation with buffered heparin from plasma in 80 healthy subjects with different serum LDL-C levels. Subjects with a high atherogenic risk had significantly higher plasma DC, MDA, and PUFA levels, but lower vitamin E/TC values and AOA than subjects with low atherogenic risk. Endogenous DC and copper-induced MDA levels in the LDL fraction were increased in subjects with serum LDL-C levels higher than 4.14 mM compared with those with normal LDL-C levels. In conclusion, this study clearly indicates that a disturbance in serum pro-oxidant-antioxidant balance and an increase in LDL oxidation are concomitant with higher TC and LDL-C and lower HDL-C levels in the serum.     

Further reduction of low-density lipoprotein cholesterol and C-reactive protein with the addition of ezetimibe to maximum-dose rosuvastatin in patients with severe hypercholesterolemia

BackgroundPatients with severe hypercholesterolemia, including familial hypercholesterolemia, are considered at high risk for coronary artery disease and often prove difficult to treat to current low-density lipoprotein cholesterol (LDL-C) guidelines.MethodsIn this open-label, 12-week substudy within a larger trial, ezetimibe 10 mg was added to stable therapy with rosuvastatin 40 mg (± bile acid sequestrant/niacin) in 107 patients with severe hypercholesterolemia who had not achieved LDL-C goal of <100 mg/dL.ResultsPrior to the start of rosuvastatin treatment, on diet alone, mean LDL-C levels were 291 ± 59 mg/dL and decreased to 141 ± 30 mg/dL on rosuvastatin 40 mg daily at the substudy baseline prior to ezetimibe. After 12 weeks, the addition of ezetimibe produced an additional 15% ±9% reduction in LDL-C (P < 0.001) compared to pre-rosuvastatin levels and a mean LDL-C of 103 ± 27 mg/dL, resulting in 59% of patients reaching their LDL-C goals. The combination reduced LDL-C by 65% ± 9% from diet alone. Combination with ezetimibe also produced significant additional percent reductions in non–high-density lipoprotein (14%), apolipoprotein B (10%), and triglycerides (6%). Median C-reactive protein was reduced 54% (P < 0.001) by the combination compared with diet alone, a further incremental reduction of 13% (P < 0.001) with the addition of ezetimibe. The combination was well tolerated, with no patients developing myopathy or clinically significant elevations of creatine kinase or transaminases.ConclusionsThe combination of rosuvastatin 40 mg and ezetimibe 10 mg offers the most effective LDL-C–lowering therapy yet reported, and is helpful in achieving lipid goals and reducing C-reactive protein levels in high-risk patients with severe hypercholesterolemia, including familial hypercholesterolemia.     

Changes in attainment of lipid goals by general practitioners and specialists in patients at high cardiovascular risk in Hungary during 2004-2008

Introduction

Lipid-lowering therapy should achieve target levels. We assessed the change of the achievement of targets and the mean low-density lipoprotein cholesterol (LDL-C) levels in high-risk Hungarian patients.

Material and methods

Six studies performed with patients of general practitioners (GPs) and specialists between 2004 and 2008 were evaluated: 9,508 patients from GPs and 2809 from specialist practices (total 12,317).

Results

During this 4-year period the LDL-C level decreased by 0.73 mmol/l and the LDL-C goal achievement rate increased from 14 to 32% in patients treated by GPs. LDL-C showed a decrease of 0.48 mmol/l and the goal achievement rate changed from 20 to 43% in patients treated by specialists. In the majority of the patients not achieving the LDL-C goal (57% for specialists and 89% for GPs) there was no modification in the current therapy. In addition to emphasizing the priority of LDL-C lowering, we should also strive for residual risk reduction, which means raising high-density lipoprotein cholesterol (HDL-C) and lowering triglyceride levels. There was no significant improvement in HDL-C or triglyceride levels during the examined period.

Conclusion

More attention needs to be paid to changing treatment of patients to achieve target levels.     

Serum lipoprotein cholesterols in older oarsmen

We evaluated effects of age and rowing on concentrations of lipids and lipoprotein cholesterols in the blood. Maximal oxygen uptake (VO_2max), and concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured in 17 oarsmen [mean (SD)] [age 64 (4) years, body mass 69 (6) kg] and in sedentary men [age 65 (3) years, body mass 70 (7) kg] who were matched on the basis of body size. Also the variables were obtained from young oarsmen [age 22 (2) years, body mass 70 (4) kg] and young sedentary men [age 22 (3) years, body mass 69 (7) kg]. The percentage body fat of the older oarsmen was lower than that of the older sedentary men [18 (4)% compared to 23 (4)%, P<0.05], but it was similar to that of the young sedentary men [17 (4)%]. Although older oarsmen possessed a lower VO_2max than the young oarsmen [3.0 (0.4) l·min^–1 compared to 4.1 (0.3) l·min^–1, P<0.01], they showed a VO_2max similar to that of the young sedentary men [3.1 (0.5) l·min^–1] but a higher value than obtained from the older sedentary men [2.2 (0.3) l·min^–1, P<0.05]. Although the indices of risk factors for coronary artery disease in the older oarsmen were higher than those in the young oarsmen [LDL-C/HDL-C 1.7 (0.2) compared to 1.3 (0.4), TC/HDL-C 3.1 (0.2) compared to 2.6(0.4), P<0.05], they were lower than those in both the older [2.1 (0.3), 3.6 (0.3), P<0.05] and the young sedentary men [2.1 (0.4), 3.5 (0.4), P<0.05]. The results suggest that rowing is an appropriate type of exercise for the promotion of health. Electronic Publication     

汉族人群IL10基因多态性与血脂水平的关系

目的探讨正常汉族人群白细胞介素10（interleukin 10，IL10）基因多态性与血脂水平的关系。方法应用PCR限制性片段长度多态性分析法，检测200名汉族正常人IL10基因启动子区的3个多态位点-1082、-819和-592的各种基因型的分布，并分析它们与血清脂蛋白浓度相应的关系。结果IL10—592（AA、CA、CC）和-819位点（CC、CT、TT）各基因型间的血脂水平的差异无统计学意义（P〉0．05）；IL-10—1082位点，GA基因型与从型相比，高密度脂蛋白浓度显著增高[（1．514±0．501）mmol／LVS．（1．261±0．346）mmol／L，t=-2．225，P=0．028]，甘油三酯浓度降低[（1．701±1．836）mmol／LV8．（0．981±0．314）mmol／L，Z=-2．096，P=0．036]，但总胆固醇、极低密度脂蛋白、低密度脂蛋白血清浓度间差异无统计学意义。结论 IL-10启动区-1082位点G／A基因多态性与血清甘油三酯及高密度脂蛋白浓度相关。     

Lipid-lowering therapy in older persons

Numerous randomized, double-blind, placebo-controlled studies and observational studies have shown that statins reduce mortality and major cardiovascular events in older high-risk persons with hypercholesterolemia. The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids, age, or gender. The updated National Cholesterol Education Program III guidelines state that in very high-risk persons, a serum low-density lipoprotein (LDL) cholesterol level of < 70 mg/dl (1.8 mmol/l) is a reasonable clinical strategy for moderately high-risk persons (2 or more risk factors and a 10-year risk for coronary artery disease of 10% to 20%), and the serum LDL cholesterol should be reduced to < 100 mg/dl (2.6 mmol/l). When LDL cholesterol-lowering drug therapy is used to treat high-risk persons or moderately high-risk persons, the serum LDL cholesterol should be reduced by at least 30% to 40%. The serum LDL cholesterol should be decreased to less than 160 mg/dl in persons at low risk for cardiovascular disease. Addition of other lipid-lowering drugs to statin therapy has not been demonstrated to further reduce cardiovascular events and mortality.