Incorporating Lipoprotein Number Into Treatment Of Lipoprotein Disorders

Natural Cholesterol Guide

Lower Cholesterol Guide

Get Instant Access

Because public health efforts and the direction of clinical research have been based around the cholesterol model for so long, a fundamental change to a measure of atherogenic lipoprotein number could have important drawbacks. First, most of the evidence base is reported in terms of ~LDL-C. Indeed, the reliance on ~LDL-C is so ingrained that it almost requires researchers to reinterpret studies that actually measured LDL-C, just to make the results align with studies that used the weaker surrogate, ~LDL-C (2). Switching entirely to lipoprotein number would steer researchers into uncharted waters, with comparatively little evidence to guide them. Second, as Grundy (28) points out, the hugely successful efforts to educate physicians and patients about the evidence-based supremacy of LDL-C might make it hard to reorient prevention efforts along the lines of lipoproteins. Third, the additional cost of measuring lipoprotein number is not trivial. Although all are valid concerns, we doubt they will prove insurmountable.

Grundy (10,28) has proposed incremental strategies, later adopted by the CCS (4) and the Canadian Diabetes Association (41), that have potential value. These clinical guidelines introduce measures of particle number alongside the traditional cholesterol surrogates (Table 2). Such strategies maintain the use of ~LDL-C but add apoB as an alternate target of therapy. Thus, a patient who has reached the ~LDL-C goal but still has an elevated apoB likely has small, dense LDL that represents further risk that is undetectable by the ~LDL-C alone.

The ATP published an interim report in 2004 (ATP-'04) that adapted the goals from the ATP-III, based on insights from five trials not included in the original report (2). Two of these trials reaffirmed the ATP-III contention that the minimum acceptable goal for high-risk patients is an ~LDL-C <100 mg/dL. The ATP-III had also reported that the suggestion by several small studies to lower ~LDL-C to 70-80 mg/dL was even better (1). Two new trials further support lowering ~LDL-C to this level (57,58); accordingly the ATP-'04 supports the tentative goal of ~LDL-C < 70 mg/dL and non-HDL < 100 mg/dL in selected patients at very high risk, recognizing that several pending studies will provide even more insight (2). Unfortunately, neither of the new studies has reported on changes in apoB at this time (57,58), though one did directly measure LDL-C (57). We believe that the continued reliance on LDL-C causes problems of interpretation in populations that have lower LDL-C at baseline. If the approximation unravels with LDL-C at lower levels (12,26,28), and direct techniques are also error prone (14), how can researchers be sure that these biases do not influence their interpretations? Aware of the problems this causes, the ATP in a section of the ATP-'04 report went to great pains to reinterpret one of the studies (57) in an effort to resolve this cognitive dissonance (2). We sympathize, because we also have to negotiate the same analytic contortions to get around the deficiencies of LDL-C. Though we have incorporated the lower ~LDL-C goal into our clinical practice, we submit that if researchers and clinicians are going to delve into this range of LDL levels, it would help also to follow a marker that has more signal and less noise.

We suggest that a practical way to approach hyperlipidemia is first to dichotomize patients into those with isolated ~LDL-C elevations and those with atherogenic dyslipide-mia (2). Those with isolated hypercholesterolemia would be managed according to the current ATP-III/ATP-'04 recommendations. Those with atherogenic dyslipidemia would have an additional target of therapy based on some marker of LDL particle number (either apoB or directly measured LDL particle number). Although the superior evidence base and cost favor apoB for this purpose, assessing particle number by the NMR technique is a promising alternative (10). We agree with the Canadian guidelines that a measure of particle number should be an alternative to the primary (i.e., ~LDL-C) goal (4, 41), rather than an alternative to the secondary, non-HDL-C goal (10,28). Linking it to the ATP-III non-HDL-C goal might unnecessarily limit efforts to improve risk detection to those with TGs >200 mg/dL. We have outlined our approach in Fig. 3, which refers to Table 3 for

Fig. 3. A New approach to managing high cholesterol. Along with Table 3, our approach reinforces the use of ~LDL-C goals by adding some marker of LDL particle number, such as apoB or directly measured LDL particle number. Because isolated elevations ofLDL-C are less likely to be associated with an invalid LDL approximation, we typically do not follow the additional marker in this setting. If a patient with an isolated elevation of LDL-C has a condition that invalidates the approximation, then we will do one of two things. The first is to measure LDL-C by P -quantification (because many of the other direct techniques are unreliable). The second is simply to follow the additional marker. In patients with features of atherogenic dyslipidemia, we routinely follow the additional marker along with LDL-C.

Fig. 3. A New approach to managing high cholesterol. Along with Table 3, our approach reinforces the use of ~LDL-C goals by adding some marker of LDL particle number, such as apoB or directly measured LDL particle number. Because isolated elevations ofLDL-C are less likely to be associated with an invalid LDL approximation, we typically do not follow the additional marker in this setting. If a patient with an isolated elevation of LDL-C has a condition that invalidates the approximation, then we will do one of two things. The first is to measure LDL-C by P -quantification (because many of the other direct techniques are unreliable). The second is simply to follow the additional marker. In patients with features of atherogenic dyslipidemia, we routinely follow the additional marker along with LDL-C.

specific goals based on the patient's underlying risk. The approach retains the use of ~LDL-C but reinforces treatment goals with apoB or LDL particle number in patients with features of atherogenic dyslipidemia, in which ~LDL-C is least reliable. A patient with isolated elevations of ~LDL-C need not have additional labs, provided that there are no clinical factors that invalidate the approximation (Table 1).

We believe that incorporating measures of lipoprotein number will overcome the numerous limitations of the LDL approximation, thereby improving the detection of at-risk patients. More important, this approach maintains links to clinical trial evidence by supporting, rather than supplanting, the LDL approximation. This algorithm should capture most of the residual risk related to the other markers discussed herein, except for Lp(a). We typically reserve Lp(a) for patients who have a family history of premature disease but lack a personal history of obvious risk factors. Lp(a) could also be used ifthe clinician suspects that it constitutes a significant confounder for LDL-C, e.g., in an African-American patient whose LDL-C seems to be unusually resistant to statin therapy.

Was this article helpful?

0 0
Lower Your Cholesterol In Just 33 Days

Lower Your Cholesterol In Just 33 Days

Discover secrets, myths, truths, lies and strategies for dealing effectively with cholesterol, now and forever! Uncover techniques, remedies and alternative for lowering your cholesterol quickly and significantly in just ONE MONTH! Find insights into the screenings, meanings and numbers involved in lowering cholesterol and the implications, consideration it has for your lifestyle and future!

Get My Free Ebook


Post a comment