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非诺贝特与他汀联用降低大血管剩留风险——Robert S. Rosenson教授专访

作者:国际循环网   日期:2011/9/27 13:49:59

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他汀降LDL-C治疗是目前CVD预防的基石,但其为糖尿病患者带来的获益有限。荟萃分析显示,他汀治疗下心血管剩留风险居高不下是医学界面临的重大挑战。剩留风险存在的根源是高TG与低HDL-C以及LDL-C亚类(LDL-P)的异常,并将与LDL-C一起成为高TG患者治疗的共同首要目标。

  International Circulation:Statins has done a good job for cardiovascular (CV) risk reduction. But patients on-treatment with statins are still at high CV risk as shown in the TNT/PROVE IT-TIMI 22 trials. Which factors are the major causes resulting in the residual risks?
  Prof- Robert Sidney Rosenson: The residual risks for individuals treated with a statin is often related to low levels of HDL-cholesterol and high triglycerides. We also know that for patients with atherogenic dyslipidemia have cholesterol depleted LDL particles and so when these patients are on a statin treatment regimen they may have excellent cholesterol values but still have excess number of LDL particles. If we do not measure LDL concentrations or its surrogate Apo-B we may be missing a very important contributing factor to residual cardiovascular risk and also a very important opportunity to identify prevention strategies in those individuals.
  International Circulation: The independent association of hypertriglycerideamia with CVD risks remains controversial. Is the evidence base of the association of atherogenic dyslipidemia with residual risks is sufficient?
  Prof- Robert Sidney Rosenson: It is very difficult to determine whether triglycerides are a risk factor or a risk marker. And this is because high triglyceride levels are associated with other lipoprotein abnormalities, they are inversely related to HDL cholesterol, positively associated with the number of LDL particles and positively associated with haemostatic abnormalities such as fibrinogen, plasminogin activator inhibitor and elevated blood viscosity. For these reasons it has been very difficult to decipher whether it is a risk factor or risk marker.
  International Circulation: The ATP III guidelines published in 2001 suggests that the primary goal for hypertriglycerideamic patients is still LDL-C lowering by statins.  Based on the data from Field and Accord, do you think that such a strategy is too conservative and should we conduct a more aggressive strategy aiming at hypertriglycerideamia?
  Prof- Robert Sidney Rosenson: The ATP guidelines are cholesterol based guidelines and from my perspective they are very myopic. I think without a doubt the new update in the guidelines will include non HDL as a primary co target. Non HDL, incorporates the risk associated with LDL and VLDL particles. I am hoping that the use of non HDL cholesterol will encourage physicians to pay more attention to the triglycerides or the VLDL particles contributions to the LDL associated risk.
  International Circulation: The ATP guideline has not been updated for 10 years. Yet sub-analysis of ACCORD trial and FIELD study have provided new data for cardiovascular protective benefits of lowering TG by finofibrate in a subgroup patients with high TG level. What are the major implications of these new data on clinical practice? If this protection benefit only diabetic patients?
  Prof- Robert Sidney Rosenson: The implications are that if your LDL cholesterol is reduced to less than 80mg per deciliter and you have elevated triglycerides and low HDL, your risk of having a cardiovascular event is substantially higher in the next 5 years, specifically 7% than those without dyslipidemia. If you are treating your patients with combination therapy such as with a statin and fenofibrate you can reduce that risk dramatically. This whereby, you can produce an absolute 5% risk reduction from the combination of two agents versus the use of a statin alone.
  International Circulation: Based on available clinical research data including previous HHS,BIP,VA-HIT, and recent ACCORD trial and FIELD study, what are the major implications of these findings for identifying the best candidates for mono- or combo- therapy of Feno & Statin in your opinion? Do you have any recommendations for the most common group of patients who have CHD with elevated TG or/and low HDL-C with or without T2DM?
  Prof- Robert Sidney Rosenson: Based on the evidence from statin therapy, most of our patients are going to be treated with a statin. The ACCORD trial looked at the background of statin therapy and asked the question whether the addition of fenofibrate towards simvastatin provided an incremental benefit in comparison to simvastatin alone. In the sub-group which had elevated triglycerides and low levels of HDL cholesterol there was a benefit on macro-vascular events as well as micro-vascular disease.
  International Circulation: How do you apply the cut-points of initiating TG lowering therapies for  hyperlipidemia in your daily practice? if co-morbidities such as coronary heart disease or type 2 diabetes mellitus should be taken into consideration?
  Consistently, when the levels of triglycerides are greater or equal to 200mg/dl there is an increased risk of cardiovascular disease. This has been established in epidemiological studies and it has been established in clinical trials and in that subgroup which were treated with a triglyceride lowering agent such as a fibrate they actually derive benefit from that triglyceride lowering treatment. When the triglycerides are not elevated you are not addressing members of a population who is an ideal candidate for the macro-vascular protection with fibrate therapy. One of the very important issues which needs to be explored is the use of fibrates to reduce micro-vascular complications related to diabetes even in those individuals who do not have elevated triglyceride levels.

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