Rationale and design of MultiSELECt: A European Multicenter Study on the Effect of Lipoprotein(a) Elimination by lipoprotein apheresis on Cardiovascular outcomes.

BACKGROUND: Dyslipidemia is a well-known risk factor for atherosclerosis and subsequent cardiovascular disease (CVD). While low density lipoprotein cholesterol (LDL-C) is well-established and taken into consideration for risk management and therapy, lipoprotein(a) is another established CVD risk factor frequently not undergoing screening due to a lack of medical treatment options. For patients suffering from CVD due to massive elevation of Lp(a) in presence of normal LDL-C levels, lipoprotein apheresis is the only available treatment option. While this constellation is an accepted indication for lipoprotein apheresis (LA) in Germany, prospective studies including a control group are still lacking. OBJECTIVE: Primary objective of this trial is to evaluate the clinical benefit of lipoprotein apheresis on myocardial infarction, PCI, CABG and death from cardiovascular disease in subjects with elevated Lp(a). This study evaluates the clinical benefit of weekly LA in subjects with progressive cardiovascular disease, as accepted by the German Federal Joint Committee (treatment group). Comparator will be well-matched subjects under maximum tolerated lipid lowering therapy without access to LA treatment (control group). METHODS: MultiSELECt, is a prospective, multicenter, multinational, two-arm matched-pair cohort study designed to directly compare subjects with significantly elevated Lp(a) approved for LA subsequently undergoing weekly apheresis treatment versus a continuation of maximal medical therapy. The follow-up period will be 2 years after the baseline visit and until at least 60 events of the primary end-point occurred in the control group. A central trial expert committee will review all subjects with respect to their potential indication for LA according to established German guidelines in a blinded fashion. All control subjects will be contacted monthly via telephone visits to compensate for the more frequent visits during apheresis. Approximately 150 matched pairs will be necessary to detect an event reduction of at least 10% in subjects under LA treatment. CONCLUSION: The MultiSELECt trial provides the unique opportunity to demonstrate the efficiency of LA on CVD in patients with elevated Lp(a) under strongly controlled conditions.

Efficacy, safety, and tolerability of long-term lipoprotein apheresis in patients with LDL- or Lp(a) hyperlipoproteinemia: Findings gathered from more than 36,000 treatments at one center in Germany.

LDL cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are main risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 36,745 LA treatments of 118 patients with CVD in a retrospective, monocentric study. Indications were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (n = 35). Average age of patients at start of LA treatment was 58.1 years for males and 62.5 years for females. Medium interval between the first cardiovascular event and LA treatment was 6.4 ± 5.6 years and the average LA treatment period was 6.8 ± 4.9 years. On average treatments were performed once a week, via peripheral venous access in 79.3% of non-hemodialysis patients. In patients with hypercholesterolemia initial pre-LA LDL-C was lowered from 176.4 ± 67.0 mg/dL by 66.7 ± 10.8% per session, achieving a long-term interval mean value of 119.8 ± 34.7 mg/dL, i.e. reduction by 32.1 ± 19.6% (p < 0.0001). In patients with isolated elevated Lp(a) initial pre-LA Lp(a) was lowered from 127.2 ± 67.3 mg/dL by 66.8 ± 5.8% per session, achieving a long-term interval mean value of 60.0 ± 19.5 mg/dL, i.e. reduction by 52.8 ± 23.0% (p < 0.0001). After start of LA the average annual rate of major adverse coronary events (MACE) of all patients declined by 79.7% (p < 0.0001). Subgroup analysis showed decline by 73.7% (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4% (p < 0.0001) in patients with isolated elevated Lp(a). Adverse events (AE) occurred in 1.1% of treatments. LA treatment of patients with high risk for CVD due to LDL and/or Lp(a) hyperlipoproteinemia was effective, safe, and well tolerated. The number of cardiovascular events, at least during a six-year period, declined by 80%.

Adiponectin and risk of coronary heart disease in apparently healthy men and women (from the EPIC-Norfolk Prospective Population Study).

The objective of the present study was to evaluate the association between adiponectin levels and incidence of coronary heart disease (CHD). We performed a prospective case-control analysis nested in the EPIC-Norfolk cohort. Participants were apparently healthy men and women 45 to 79 years of age who developed fatal or nonfatal CHD during an average follow-up period of 7.7 ± 1.1 years. In total 1,035 participants with incident CHD were matched for age, gender, and enrollment time to 1,920 controls who remained free of CHD over the study follow-up. Baseline nonfasting plasma adiponectin concentrations were determined by enzyme-linked immunosorbent assay. Adiponectin levels were lower in participants with CHD than in matched controls (men 8.74 vs 9.13 µg/ml, p = 0.01; women 12.6 vs 13.4 µg/ml, p = 0.03). A 1-µg/ml increment in adiponectin was associated with decreased CHD risk (odds ratio 0.78, 95% confidence interval 0.63 to 0.96, p = 0.02, in men; odds ratio 0.73, 95% confidence interval 0.55 to 0.96, p = 0.03, in women). However, this association was no longer significant after adjustment for established cardiovascular risk factors. Stratification of participants according to metabolic syndrome status showed that men and women with metabolic syndrome had a higher CHD risk, irrespective of their adiponectin levels. In conclusion, although a low adiponectin concentration is associated with an increased CHD risk, findings of the present study do not suggest that its measurement is useful to refine CHD risk assessment once traditional risk factors and clinical features of the metabolic syndrome have been considered.

[Optimal lipid treatment: possibilities and current limitations]. / Möglichkeiten und Grenzen der modernen Lipidtherapie.

Prevention is a major contributor to the decline in cardiovascular morbidity and mortality. Cardiovascular diseases still are the leading cause of death (42%) in Germany and indicate unmet preventive needs. Limitations of healthy lifestyle, the basis of many recommendations, include insufficient compliance and efficacy in individual cases. In their latest metaanalysis the Cholesterol Treatment Trialists' Collaborators showed updated estimates of treatment effects of statins including more or less intensive regimens.The average reduction in major vascular events was 21% per 1.0 mmol/l reduction in LDL cholesterol. Appropriateness of receiving lipid modulating treatment in the population will be discussed in the light of controversial recommendations in treatment strategies. Residual risk in statin treated patients may be ameliorated by options beyond LDL-lowering. Suggestions for clinical practice are provided on the background of clinical relevant characteristics of current lipid lowering drugs and future developments are outlined.

Association of lipids and lipoprotein level with total mortality and mortality caused by cardiovascular and cancer diseases (Poland and United States collaborative study on cardiovascular epidemiology).

This study evaluates the relation between total serum cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol, and subsequent total, cardiovascular, and cancer mortality. These data are from 4,946 US and 5,198 Polish men and women aged 35 to 64 years at baseline with mortality follow-up over 13 years. Total cholesterol showed a U-shaped or J-shaped relation to age-adjusted total and cancer mortality across all samples, with significance only in Polish women. The multivariable adjusted relative risk for total and cancer mortality was higher in the lowest cholesterol category only in Poland and significant only for cancer. Cardiovascular mortality was positively related to cholesterol, but only in Polish men and US women was mortality significantly higher in the highest versus the lowest cholesterol category. The multivariable adjusted relative risk of cardiovascular death was greater in the highest versus the lowest cholesterol category, but this trend was significant only in the US. HDL cholesterol was inversely related to total (significant only in US men) and cardiovascular mortality (significant only in US and Polish men). A similar, but not significant, association of HDL cholesterol was found with cancer mortality. The multivariable adjusted relative risk of total mortality was inversely related to HDL cholesterol significant in both the US and Poland. The relative risk of cardiovascular mortality was significantly lower at higher HDL cholesterol levels in all samples. The relative risk of cancer mortality was highest and significant at the lowest HDL cholesterol level in the US and Poland. Elevated triglycerides were associated with increased risk of total and cardiovascular mortality, but this trend was significant only in the US. Cancer mortality was not significantly related to triglycerides. The present study indicates that in geographically and culturally diverse populations, the relation of lipids with cardiovascular mortality is similar. The relation with total and cancer mortality varies by country, gender, and lipids. This suggests that relations of total and cancer mortality with lipids or lipoproteins are weaker than associations with cardiovascular mortality.

[Motivations for determining biological aging]. / Motivationen zur Bestimmung des biologischen Alters.

Studies to determine the biological age of a person are a major concern of gerontological research today. The use of test batteries is now a proven method, and the procedure developed in Leipzig covers 47 parameters including physical, mental, and social data. It can be seen from the related findings that this approach is suitable for dealing with specific questions in gerontology. These include the detection of medical risk factors and environmental effects, and confirmation of intervention strategies. The prime motives behind these studies then seem to be in keeping with practical requirements.

Serum linoleic acid and cardiovascular death in postinfarction middle-aged men.

Linoleic acid in serum total lipids was the first variable in the stepwise regression analysis of metabolic, nutritional and cardiovascular factors in a secondary preventive study of postinfarction middle-aged men. It was followed in the regression analysis where the dependent variable was cardiovascular death by previous myocardial infarction, heart volume index and hyperlipoproteinaemia. Linoleic acid was the only fatty acid entering the regression. Unlike other fatty acids, it exhibited by its low percentage an accumulation of deaths. The decreased percentage of linoleic acid was also evident in the comparison of fatty acid patterns of cardiovascular deaths to age- and triglyceride-matched men free from ischaemic heart disease. This study confirms prospective associations found in previously healthy men. Conclusions are drawn about the relevance of low serum linoleic acid to long term prognosis after MI.