Because LDL-cholesterol (LDL-C) is a modifiable risk for coronary heart disease, its routine measurement is recommended in the evaluation and management of hypercholesterolemia. We critically examine ...here the new homogeneous assays for direct determination of LDL-C.
This review relies on published studies and data of the authors using research and routine methods for LDL-C determination. We review experience with methods from their earlier use in lipid research laboratories through the transition to routine clinical testing and the recent development of homogeneous assays. We focus on comparative evaluations and characterizations and the performance of the assays.
Homogeneous assays seem to be able to meet current National Cholesterol Education Program (NCEP) requirements for LDL-C testing for precision (CV <4%) and accuracy (bias <4%), when samples collected from nonfasting individuals are used. In addition, all five currently available assays have been certified by the Cholesterol Reference Methods Laboratory Network. The homogeneous methods also appear to better classify individuals into NCEP cutpoints than the Friedewald calculation. However, the limited evaluations to date raise questions about their reliability and specificity, especially in samples with atypical lipoproteins.
Available evidence supports recommending the homogeneous assays for LDL-C to supplement the Friedewald calculation in those cases where the calculation is known to be unreliable, e.g., triglycerides >4000 mg/L. Before the homogeneous assays can be confidently recommended to replace the calculation in routine practice, more evaluation is needed.
Background —Elevated plasma concentrations of C-reactive protein (CRP) are associated with increased cardiovascular risk. We evaluated whether long-term therapy with pravastatin, an agent that ...reduces cardiovascular risk, might alter levels of this inflammatory parameter. Methods and Results —CRP levels were measured at baseline and at 5 years in 472 randomly selected participants in the Cholesterol and Recurrent Events (CARE) trial who remained free of recurrent coronary events during follow-up. Overall, CRP levels at baseline and at 5 years were highly correlated ( r =0.60, P <0.001). However, among those allocated to placebo, median CRP levels and the mean change in CRP tended to increase over time (median change, +4.2%; P =0.2 and mean change, +0.07 mg/dL; P =0.04). By contrast, median CRP levels and the mean change in CRP decreased over time among those allocated to pravastatin (median change, −17.4%; P =0.004 and mean change, −0.07 mg/dL; P =0.002). Thus, statistically significant differences were observed at 5 years between the pravastatin and placebo groups in terms of median CRP levels (difference, −21.6%; P =0.007), mean CRP levels (difference, −37.8%; P =0.002), and absolute mean change in CRP (difference, −0.137 mg/dL; P =0.003). These effects persisted in analyses stratified by age, body mass index, smoking status, blood pressure, and baseline lipid levels. Attempts to relate the magnitude of change in CRP to the magnitude of change in lipids in both the pravastatin and placebo groups did not reveal any obvious relationships. Conclusions —Among survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up. In contrast, randomization to pravastatin resulted in significant reductions in this inflammatory marker that were not related to the magnitude of lipid alterations observed. Thus, these data further support the potential for nonlipid effects of this agent.
Abstract
A continual trend of annual growth can be seen within research devoted to the discovery and validation of disease biomarkers within both the natural and clinical sciences. This expansion of ...intellectual endeavours was quantified through database searches of (a) research grant awards provided by the various branches of the National Institutes of Health (NIH) and (b) academic publications. A search of awards presented between 1986 and 2009 revealed a total of 28,856 grants awarded by the NIH containing the term "biomarker". The total funds for these awards in 2008 and 2009 alone were over $2.5 billion. During the same respective timeframes, searches of "biomarker" and either "discovery", "genomics", "proteomics" or "metabolomics" yielded a total of 4,928 NIH grants whose combined funding exceeded $1.2 billion. The derived trend in NIH awards paralleled the annual expansion in "biomarker" literature. A PubMed search for the term, between 1990 and 2009, revealed a total of 441,510 published articles, with 38,457 published in 2008. These enormous investments and academic outputs however have not translated into the expected integration of new biomarkers for patient care. For example no proteomics derived biomarkers are currently being utilized in routine clinical management. This translational chasm necessitates a review of the previously proposed biomarker definitions and evaluation schema. A subsequent discussion of both the analytical and pre-analytical considerations for such research is also presented within. This required knowledge should aid scientists in their pursuit and validation of new biological markers of disease.
Abstract Objective To examine prospectively the association of total and high molecular weight (HMW) adiponectin, and HMW/total adiponectin ratio with risk of incident coronary heart disease (CHD) in ...women, and to examine to what extent adjustment for potentially intermediary variables would explain this association. Methods and results Among 30,111 women from the Nurses’ Health Study, 468 women developed non-fatal myocardial infarction or fatal CHD during 14 years of follow-up. Using risk set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. Adjusted for matching factors, parental history of myocardial infarction, hormone replacement therapy, alcohol consumption, physical activity, body mass index, hypertension, and low-density lipoprotein cholesterol levels, the relative risk in the highest versus lowest quintile was 0.50 (95%-CI 0.33–0.75; p trend = 0.001) for total adiponectin, 0.53 (95%-CI 0.35–0.80; p trend = 0.004) for HMW adiponectin, and 0.63 (95%-CI 0.43–0.93; p trend = 0.03) for HMW/total adiponectin ratio. After adjustment for diabetes, HDL-cholesterol, HbA1c, and CRP these associations were attenuated and no longer significant (RRs, 0.84; 95%-CI 0.53–1.33; p trend = 0.62; 0.95; 95%-CI 0.60–1.52; p trend = 0.98; 0.97; 95%-CI 0.64–1.47; p trend = 0.80). Conclusions High levels of total and HMW adiponectin, and HMW/total adiponectin ratio are associated with a lower risk of CHD among women. HMW adiponectin and HMW/total adiponectin ratio are not more closely related to risk than total adiponectin. These associations are largely mediated by parameters related to glucose and lipid metabolism and inflammation, especially HDL-cholesterol levels.
...the number of scientific journals indexed by the Web of Science has increased by 66% since 2000, from 7383 to 12 271. According to an investigation by the German Public Broadcasters NDR and WDR, ...together with the Süddeutsche Zeitung Magazin, predatory journals have involved ^400 000 scientists globally. ...the latter are still the largest group of authors. There is evidence that some authors purposefully publish in these journals to create a quantitatively impressive publication list, so as to mislead promotion committees. ...maybe the correct analogy is not of predator and prey, but one of symbiosis.
Treatment with lovastatin reduced the risk of coronary events.
Both the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) and the West of Scotland Coronary Prevention Study ...demonstrated that inhibitors of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (statins) reduce the risk of first coronary events.
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However, the use of statins for primary prevention has not been widely adopted, in part because the number of persons who need to be treated to prevent one clinical event is relatively large and the cost of this approach is substantial.
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A method of distinguishing high-risk from low-risk patients might make possible better targeting of statin therapy for primary prevention.
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For example, restricting statin use . . .
Sudden cardiac death (SCD) is an important cause of mortality even among apparently healthy populations. However, our ability to identify those at risk for SCD in the general population is poor, and ...more specific markers are needed.
To compare and contrast the relative importance of C-reactive protein (CRP), homocysteine, and lipids as long-term predictors of SCD, we performed a prospective, nested, case-control analysis involving 97 cases of SCD among apparently healthy men enrolled in the Physician's Health Study. Of these plasma markers measured, only baseline CRP levels were significantly associated with the risk of SCD over the ensuing 17 years of follow-up (P for trend=0.001). The increase in risk associated with CRP levels was primarily seen among men in the highest quartile, who were at a 2.78-fold increased risk of SCD (95% CI 1.35 to 5.72) compared with men in the lowest quartile. These results were not significantly altered in analyses that (in addition to the matching variables of age and smoking status) controlled for lipid parameters, homocysteine, and multiple cardiac risk factors (relative risk for highest versus lowest quartile 2.65, 95% CI 0.79 to 8.83; P for trend=0.03). In contrast to the positive relationship observed for CRP, neither homocysteine nor lipid levels were significantly associated with risk of SCD.
These prospective data suggest that CRP levels may be useful in identifying apparently healthy men who are at an increased long-term risk of SCD.
Accumulating data suggest a link between blood pressure and vascular inflammation.
We examined the relationship between blood pressure, C-reactive protein (CRP), and incident first cardiovascular ...events among 15 215 women followed prospectively over a median of 8.1 years. In cross-sectional analyses at baseline, median levels of CRP for women with blood pressure <120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94, and > or =160/95 mm Hg were 0.96, 1.42, 2.20, 2.82, and 3.34 mg/L, respectively (P for trend <0.0001). Increasing categories of blood pressure were significant predictors of CRP levels at baseline. In prospective analyses, both elevated CRP levels (> or =3 mg/L) and increasing categories of blood pressure were independent determinants of future cardiovascular events, and CRP had incremental prognostic value at all levels of blood pressure. The adjusted hazard ratio for women with blood pressure > or =160/95 mm Hg and CRP levels > or =3 mg/L was 8.31 (95% CI, 4.44 to 15.55, P<0.0001) compared with those with blood pressure <120/75 and CRP levels <3 mg/L. After participants had been divided into 4 groups on the basis of CRP levels (<3 or > or =3 mg/L) and blood pressure levels (<130/85 or > or =130/85), the risk factor-adjusted hazard ratios were as follows: low CRP/low blood pressure, 1.0; high CRP/low blood pressure, 1.87 (P=0.002); low CRP/high blood pressure, 2.54 (P<0.0001); and high CRP/high blood pressure, 3.27 (P<0.0001).
CRP and blood pressure are independent determinants of cardiovascular risk, and their predictive value is additive.
Heart disease and stroke continue to be the leading causes of death in the US. As a result, investigators continue to look for new and emerging biomarkers of disease risk. Because many of these ...emerging biomarkers are not as well documented as those of conventional lipid and lipoprotein risk factors, their value in clinical practice needs to be critically appraised and appropriate guidelines developed for their proposed use.
The National Academy of Clinical Biochemistry (NACB) convened a multidisciplinary expert panel to develop laboratory medicine practice guidelines for a selected subset of these emerging risk factors as applied in a primary prevention setting of heart disease and stroke. The NACB expert panel selected lipoprotein subclasses and particle concentration, lipoprotein(a), apolipoproteins A-I and B, high sensitivity C-reactive protein (hsCRP), fibrinogen, white blood cell count, homocysteine, B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and markers of renal function as biomarkers that fell within the scope of these guidelines.
Based on a thorough review of the published literature, only hsCRP met all of the stated criteria required for acceptance as a biomarker for risk assessment in primary prevention.
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