Tuesday, October 12, 2010
CRP etnic differences.
From Heartwire CME
Ethnicity Could Muddy the Waters of CRP-Guided Statin Therapy CME
News Author: Lisa Nainggolan
CME Author: Laurie Barclay, MD
CME Released: 10/01/2010; Valid for credit through 10/01/2011
October 1, 2010 — A new meta-analysis shows that average C-reactive-protein (CRP) levels vary among races and that these differences were mostly unexplained by conventional cardiovascular risk factors [1]. The findings have led to debate over whether a single cutoff point for CRP across different ethnic groups is appropriate or not.
Lead author Dr Tina Shah (University College London, UK) told heartwire : "The average levels of CRP in different populations showed quite marked differences. We found that East Asians had quite substantially lower CRP levels compared, for example, with African American individuals. This may or may not reflect different levels of coronary risk; we don't know yet," she added.
The average levels of CRP in different populations showed quite marked differences.
And "if you're using CRP levels to perhaps prescribe statins, then it seems that this would have an impact on eligibility for statin treatment," she says, adding that these findings may be particularly relevant in the multiethnic melting pot that is the US. Shah and colleagues' study is published online September 28, 2010 in Circulation: Cardiovascular Genetics.
More Than 50% of Blacks and Hispanics Would Exceed 2 mg/L at Age 50
Earlier this year, the US FDA expanded the license for rosuvastatin (Crestor, AstraZeneca) to include its use in the prevention of cardiovascular disease in men over 50 years and women over 60 years who have one other risk factor and CRP greater than 2 mg/L, based on the findings of the JUPITER study.
But, as reported by heartwire , controversy surrounds JUPITER. Senior author of the new study, Dr Aroon D Hingorani (University College London), observes: "There is ongoing debate over the ability of CRP to predict the risk of heart disease over established cardiovascular risk factors, even in individuals of European origin, where there is the most evidence pertaining to the CRP–coronary disease association.”
And current advice on whether or not to measure CRP varies from country to country, he notes, with the US and Canada embracing the test more wholeheartedly than European countries at the moment. "The perspective from the European angle is that perhaps CRP doesn't add very much once you've already measured established risk factors," he says.
On this background, Shah et al conducted a systematic review and meta-analysis of data on 221 287 people from 89 published studies and discovered that CRP levels differed by ethnicity, even after adjustments for age, body-mass index, smoking, and polymorphisms in the CRP gene. African Americans had the highest CRP levels, with an average of 2.6 mg/L, followed by Hispanics (2.51 mg/L), South Asians (2.34 mg/L), and whites (2.03 mg/L). East Asians had the lowest CRP levels, at 1.01 mg/L.
Based on these figures, more than half of African Americans and Hispanics would likely exceed the 2-mg/L CRP threshold at 50 years of age, while less than half of East Asians would surpass this cutoff, the researchers say.
"What our study seems to indicate is that there are reasonably large differences in average CRP values between [people] of differing ancestry, and the differences are sufficiently large to have a potential impact on the eligibility for rosuvastatin treatment on the one hand and also on the interpretation of the CRP value for risk prediction on the other," says Hingorani.
This Is Nothing New, Says Ridker; A Single Cut Point Works Well
However, Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA), the lead investigator of the JUPITER study, told heartwire : "There is not much new to talk about" in this study. "Just like LDL varies a bit between ethnic groups, it has long been known that CRP levels vary a bit between ethnic groups. What the authors seem to be missing here is that vascular event rates also vary between ethnic groups and that this variation tracks with CRP levels just as you would anticipate--for example, the observation that a somewhat larger proportion of African Americans have higher CRP levels is actually a good finding, since African Americans also have higher vascular-event rates than do age-matched whites. Similarly, those of Japanese or Chinese descent have somewhat lower CRP levels and also have somewhat lower vascular risk.
There is not much new to talk about . . . . It has long been known that CRP levels vary a bit between ethnic groups.
"We obviously knew all of this back in 2003 when we started the JUPITER trial; picking a single cut point worked very well . . . as we got virtually identical risk reductions for our white and nonwhite subgroups," he says, adding that around 25% of the JUPITER population was nonwhite.
Hingorani told heartwire : "We think there is probably a positive association between CRP and [vascular] risk even in the non-European population, but whether that is sufficient for doctors to be able to interpret a CRP value in the clinical setting adequately to make decisions on statin targeting and risk prediction is uncertain."
Current Study Questions the Wisdom of a Universal Cut Point
Shah and colleagues say around five million high-sensitivity CRP tests were ordered in the US in 2007 and that the recent FDA decision to expand the label for rosuvastatin is likely to further increase the number of tests performed there.
Dr Sanjay Kaul (Cedars Sinai Medical Center, Los Angeles, CA)--who was on the FDA advisory panel deliberating on the expanded indication for rosuvastatin and who voted for approval--says this new research does complicate matters. "The current study muddies the water by suggesting an important impact of ethnic differences on CRP levels and questions the wisdom of using a universal CRP cutoff for identifying patients eligible for statin treatment.
The current study [suggests] an important impact of ethnic differences on CRP levels and questions the wisdom of using a universal CRP cutoff.
"The evidence base supporting the inclusion of CRP in CVD risk assessment is modest, incomplete, and overstated," Kaul asserts. "As with any other diagnostic or risk-prediction tests, one size does not fit all. The clinical and demographic contexts are important considerations. On the basis of the totality of evidence, calls for the widespread adoption of CRP measurement as a screening test must be regarded as premature and unwarranted."
Hingorani notes: "Whichever patient group you are seeing, it's important to focus your interest on established cardiovascular risk factors. . . . That should come first. If you are inclined to measure CRP values--which we wouldn't be in Europe--but if you are, then CRP levels need to be interpreted in the context of the ethnicity of the patient. To say much more than that is difficult at this stage.
"Hopefully, one of the aspects of this paper is that it might drive a little bit more research on the relationship between CRP and vascular risk in non-European populations," he concludes.
Shah and Hingorani have received research funding from the British Heart Foundation to study the potential role of CRP as a predictive test or therapeutic target in coronary heart disease. Hingorani has received research funding from the Medical Research Council relating to complement factor H as a potential biomarker for coronary disease; Pfizer is an industrial partner on this award. He has also received honoraria for speaking at educational meetings on coronary risk prediction, most or all of which have been donated to charity.
References
1. Shah T, Newcombe P, Smeeth L, et al. Ancestry as a determinant of mean population C-reactive protein values: implications for cardiovascular risk prediction. Circ Cardiovasc Genet 2010; DOI:10.1161/CIRCGENETICS.110.957431. Available at: http://circgenetics.ahajournals.org.
Clinical Context
Risk-prediction instruments such as the Framingham equation integrate information on established cardiovascular risk factors, but a large proportion of events occur among individuals with near-average levels of continuous risk factors or at intermediate Framingham risk. Because inflammation is increasingly implicated in the pathophysiology of atherosclerosis, CRP, a sensitive circulating biomarker of inflammation, may be potentially useful in predicting cardiovascular risk.
Statins are widely prescribed for the reduction of cardiovascular risk. One of the eligibility criteria for rosuvastatin treatment for cardiovascular disease prevention is a CRP concentration of more than 2 mg/L. To date, most observational studies of the association between CRP and cardiovascular disease risk have been performed in Europeans.
Ethnicity Could Muddy the Waters of CRP-Guided Statin Therapy CME
News Author: Lisa Nainggolan
CME Author: Laurie Barclay, MD
CME Released: 10/01/2010; Valid for credit through 10/01/2011
October 1, 2010 — A new meta-analysis shows that average C-reactive-protein (CRP) levels vary among races and that these differences were mostly unexplained by conventional cardiovascular risk factors [1]. The findings have led to debate over whether a single cutoff point for CRP across different ethnic groups is appropriate or not.
Lead author Dr Tina Shah (University College London, UK) told heartwire : "The average levels of CRP in different populations showed quite marked differences. We found that East Asians had quite substantially lower CRP levels compared, for example, with African American individuals. This may or may not reflect different levels of coronary risk; we don't know yet," she added.
The average levels of CRP in different populations showed quite marked differences.
And "if you're using CRP levels to perhaps prescribe statins, then it seems that this would have an impact on eligibility for statin treatment," she says, adding that these findings may be particularly relevant in the multiethnic melting pot that is the US. Shah and colleagues' study is published online September 28, 2010 in Circulation: Cardiovascular Genetics.
More Than 50% of Blacks and Hispanics Would Exceed 2 mg/L at Age 50
Earlier this year, the US FDA expanded the license for rosuvastatin (Crestor, AstraZeneca) to include its use in the prevention of cardiovascular disease in men over 50 years and women over 60 years who have one other risk factor and CRP greater than 2 mg/L, based on the findings of the JUPITER study.
But, as reported by heartwire , controversy surrounds JUPITER. Senior author of the new study, Dr Aroon D Hingorani (University College London), observes: "There is ongoing debate over the ability of CRP to predict the risk of heart disease over established cardiovascular risk factors, even in individuals of European origin, where there is the most evidence pertaining to the CRP–coronary disease association.”
And current advice on whether or not to measure CRP varies from country to country, he notes, with the US and Canada embracing the test more wholeheartedly than European countries at the moment. "The perspective from the European angle is that perhaps CRP doesn't add very much once you've already measured established risk factors," he says.
On this background, Shah et al conducted a systematic review and meta-analysis of data on 221 287 people from 89 published studies and discovered that CRP levels differed by ethnicity, even after adjustments for age, body-mass index, smoking, and polymorphisms in the CRP gene. African Americans had the highest CRP levels, with an average of 2.6 mg/L, followed by Hispanics (2.51 mg/L), South Asians (2.34 mg/L), and whites (2.03 mg/L). East Asians had the lowest CRP levels, at 1.01 mg/L.
Based on these figures, more than half of African Americans and Hispanics would likely exceed the 2-mg/L CRP threshold at 50 years of age, while less than half of East Asians would surpass this cutoff, the researchers say.
"What our study seems to indicate is that there are reasonably large differences in average CRP values between [people] of differing ancestry, and the differences are sufficiently large to have a potential impact on the eligibility for rosuvastatin treatment on the one hand and also on the interpretation of the CRP value for risk prediction on the other," says Hingorani.
This Is Nothing New, Says Ridker; A Single Cut Point Works Well
However, Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA), the lead investigator of the JUPITER study, told heartwire : "There is not much new to talk about" in this study. "Just like LDL varies a bit between ethnic groups, it has long been known that CRP levels vary a bit between ethnic groups. What the authors seem to be missing here is that vascular event rates also vary between ethnic groups and that this variation tracks with CRP levels just as you would anticipate--for example, the observation that a somewhat larger proportion of African Americans have higher CRP levels is actually a good finding, since African Americans also have higher vascular-event rates than do age-matched whites. Similarly, those of Japanese or Chinese descent have somewhat lower CRP levels and also have somewhat lower vascular risk.
There is not much new to talk about . . . . It has long been known that CRP levels vary a bit between ethnic groups.
"We obviously knew all of this back in 2003 when we started the JUPITER trial; picking a single cut point worked very well . . . as we got virtually identical risk reductions for our white and nonwhite subgroups," he says, adding that around 25% of the JUPITER population was nonwhite.
Hingorani told heartwire : "We think there is probably a positive association between CRP and [vascular] risk even in the non-European population, but whether that is sufficient for doctors to be able to interpret a CRP value in the clinical setting adequately to make decisions on statin targeting and risk prediction is uncertain."
Current Study Questions the Wisdom of a Universal Cut Point
Shah and colleagues say around five million high-sensitivity CRP tests were ordered in the US in 2007 and that the recent FDA decision to expand the label for rosuvastatin is likely to further increase the number of tests performed there.
Dr Sanjay Kaul (Cedars Sinai Medical Center, Los Angeles, CA)--who was on the FDA advisory panel deliberating on the expanded indication for rosuvastatin and who voted for approval--says this new research does complicate matters. "The current study muddies the water by suggesting an important impact of ethnic differences on CRP levels and questions the wisdom of using a universal CRP cutoff for identifying patients eligible for statin treatment.
The current study [suggests] an important impact of ethnic differences on CRP levels and questions the wisdom of using a universal CRP cutoff.
"The evidence base supporting the inclusion of CRP in CVD risk assessment is modest, incomplete, and overstated," Kaul asserts. "As with any other diagnostic or risk-prediction tests, one size does not fit all. The clinical and demographic contexts are important considerations. On the basis of the totality of evidence, calls for the widespread adoption of CRP measurement as a screening test must be regarded as premature and unwarranted."
Hingorani notes: "Whichever patient group you are seeing, it's important to focus your interest on established cardiovascular risk factors. . . . That should come first. If you are inclined to measure CRP values--which we wouldn't be in Europe--but if you are, then CRP levels need to be interpreted in the context of the ethnicity of the patient. To say much more than that is difficult at this stage.
"Hopefully, one of the aspects of this paper is that it might drive a little bit more research on the relationship between CRP and vascular risk in non-European populations," he concludes.
Shah and Hingorani have received research funding from the British Heart Foundation to study the potential role of CRP as a predictive test or therapeutic target in coronary heart disease. Hingorani has received research funding from the Medical Research Council relating to complement factor H as a potential biomarker for coronary disease; Pfizer is an industrial partner on this award. He has also received honoraria for speaking at educational meetings on coronary risk prediction, most or all of which have been donated to charity.
References
1. Shah T, Newcombe P, Smeeth L, et al. Ancestry as a determinant of mean population C-reactive protein values: implications for cardiovascular risk prediction. Circ Cardiovasc Genet 2010; DOI:10.1161/CIRCGENETICS.110.957431. Available at: http://circgenetics.ahajournals.org.
Clinical Context
Risk-prediction instruments such as the Framingham equation integrate information on established cardiovascular risk factors, but a large proportion of events occur among individuals with near-average levels of continuous risk factors or at intermediate Framingham risk. Because inflammation is increasingly implicated in the pathophysiology of atherosclerosis, CRP, a sensitive circulating biomarker of inflammation, may be potentially useful in predicting cardiovascular risk.
Statins are widely prescribed for the reduction of cardiovascular risk. One of the eligibility criteria for rosuvastatin treatment for cardiovascular disease prevention is a CRP concentration of more than 2 mg/L. To date, most observational studies of the association between CRP and cardiovascular disease risk have been performed in Europeans.
# posted by roodbont @ 4:56 AM 
