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Estimated GFR and risk of CVD
- Emeka Nwankwo (5 July 2009)
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eGFR exhibits a U-shaped curve of mortality
- Sunil Bhandari (5 July 2009)
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Is the cardiovascular continuum a one-way road for everybody?
- Carlos Escobar, Vivencio Barrios (6 July 2009)
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Apples are sour!
- Malvinder S. Parmar (13 July 2009)
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Measurements of kidney function in cardiovascular disease
- John A. Lee (14 July 2009)
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Emeka Nwankwo, Reader University of Maiduguri, Maiduguri, Nigeria
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The research article by Kurth and colleagues is commendable in view of the large size of the study population of female health professionals mostly white and aged >45 years at the start of the project who had a follow up of 12 years (1). They reported that “we did not observe an increased risk of any cardiovascular disease event or mortality for the more than 11,000 women with GFR between 60 and 89 ml/min/1.73m2”. While agreeing that such a finding will be a reassuring piece of information for the large percentage of the general population whose GFRs fall within that range, the study was limited by the lack of data on markers of kidney damage which should be important in categorizing kidney function in individuals with GFR >60ml/min. The KDOQI guidelines on classification work group did not consider the category of individuals with GFR 60-89 without markers of kidney damage as CKD or indeed at risk of adverse outcomes(2). It therefore appears to me that a more appropriate deduction from this study should read that “in the absence of information on urinary albumin excretion rates and other markers of kidney damage that the risk of cardiovascular disease is similar for the groups of individuals with eGFRs 60-89 and > 90ml/min/1.73m2. Reference: 1. Kurth T, de Jong PE, Cook NR, Buring JE, Ridker PM. Kidney function and risk of cardiovascular disease and mortality in women: a prospective cohort study. BMJ 2009; 338: b2392 2. NKF: K/DOQI. Definition and Classification of stages of Chronic Kidney Disease. Am J Kidney Dis. 2002; 39: Suppl 2 S46-75 Competing interests: None declared |
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Sunil Bhandari, Consultant/Honorary Clinical Reader Hull and East Yorkshire Hospitals NHS and Hull York Medical School, Kingston upon Hull, HU32JZ
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We read the interesting article and editorial on kidney function and risk of cardiovascular disease 1, 2 with great interest. We would like to suggest a U shaped rather than J shaped curve actually exists related to mortality and renal function. We agree that as well as predicting end stage renal disease, there is growing evidence that worsening chronic kidney disease carries an increasing risk of cardiovascular death3, 4 as well as all cause5 and non- cardiovascular mortality6. However we have previously shown, in a study examining the 6 year survival of over 33, 00 patients (~18,600 female and ~14700 male) aged 50 years over the full range of eGFR values, that as a marker of mortality, both low and high eGFRs are equally predictive of increased mortality7. In this study we also found that death due to cardiovascular disease increased as eGFR declined in both men and women. In addition to showing the increased mortality at low eGFR, our study has shown that the risk of death increases as eGFR increases. Indeed the ‘J’ shaped relationships between eGFR and all-cause mortality reported by others 5 actually elongates to a ‘U’ shape 7. While cardiovascular disease predominated in patients with low eGFR, respiratory and neoplastic causes appeared to account for most of the deaths in the high eGFR groups. It seems likely, therefore, that a cachexia-associated reduction in lean muscle mass is at least part of the reason for lower creatinine concentrations, especially in those patients who subsequently died from cancer. Therefore we would agree that the high eGFR maybe in part simply a limitation of the MDRD formula to predict GFR accurately in this group of patients. However as a marker of mortality, a high eGFR can be as predictive of death as low values. References 1.Weiner DE. Kidney function and the risk of cardiovascular disease. BMJ 2009: 339; 2. 2.Kurth T, de Jong PE, Cook NR, Buring JE, Ridker PM, Kidney function and the risk of cardiovascular disease and mortality in women: a prospective cohort study. BMJ 2009: 338; b2392. 3.Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005: 67; 2089-100. 4.Levey AS, Stevens LA, Hostetter T. Automatic Reporting of Estimated Glomerular Filtration Rate-Just What the Doctor Ordered. Clinical Chemistry 2006: 52; 2188. 5.Go AS, Chertow GM, Fan DJ, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004: 351;1296-305. 6.Fried LF, Katz R, Sarnak MJ, Shlipak MG, Chaves PHM, Jenny NS, et al. Kidney Function as a Predictor of Noncardiovascular Mortality. J Am Soc Nephrol 2005:16; 3728-35. 7.Cox HJ, Bhandari S, Rigby AS, Kilpatrick ES. Mortality at low and high estimated GFR values. A U- shaped curve. Nephron Clinical Practice 2008: 110; 67-72. Competing interests: Received funding support to attend National conferences from Amgen, Novartis and Roche and received honrarium from BMS, Pfizer. Has been on the advisory boear for Roche and Astellas. |
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Carlos Escobar, Cardiologist Hospital Infanta Sofia, 28702, Madrid, Spain, Vivencio Barrios
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Kurth et al found that in a large prospective cohort of women, without prior cardiovascular disease or other major disease at study entry, there was no association between mild to moderate kidney impairment and increased risk of cardiovascular disease or all cause mortality after 12 years of follow-up [1]. Only impaired kidney function (GFR <60 ml/min/1.73 m2) seemed to be associated with an increased risk of cardiovascular disease death but not other cardiovascular or mortality outcomes. It is widely accepted that cardiovascular disease evolves as a continuum, from risk factors to subclinical organ damage and finally to overt clinical cardiovascular disease. But when different compounds of this continuum are analyzed, some relevant differences begin to emerge. Thus, although LDL-cholesterol reduction is a key target to prevent the development of cardiovascular outcomes, results from different trials differ. Despite subjects at the first stages of the continuum show important benefits with a statin therapy (i.e. JUPITER and ASTEROID trials [2,3]), when cardiovascular disease is established, these benefits appears to be minor or even absent (i.e. CORONA and AURORA trials [4,5]). On the other hand, results from the meta-analysis performed by Lindholm LH et al showed that in hypertension the effect of beta blockers, compared with other antihypertensive drugs, was less than optimum, with a raised risk of stroke and no additional benefit on coronary events [6]. Even more, authors suggested that beta blockers should not remain as first choice in the treatment of essential hypertension. By contrast, nobody doubts about the benefits of beta blockers on myocardial infarction or heart failure [7]. All these data show that despite a cardiovascular continuum appears logical, it seems a tortuous continuum with different roads and pathophysiological pathways. This should be taken into account when considering the time to start the treatment for cardiovascular prevention, which drug should be preferable according to the stage and patients´ clinical characteristics and the most appropriate target for each condition according to the cardiovascular risk stratification. References: 1. Kurth T, de Jong PE, Cook NR, Buring JE, Ridker PM. Kidney function and risk of cardiovascular disease and mortality in women: a prospective cohort study. BMJ 2009; 338: b2392. 2. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al; JUPITER Trial Study Group. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009;373:1175-1182. 3. Ballantyne CM, Raichlen JS, Nicholls SJ, Erbel R, Tardif JC, Brener SJ, et al; ASTEROID Investigators. Effect of rosuvastatin therapy on coronary artery stenoses assessed by quantitative coronary angiography: a study to evaluate the effect of rosuvastatin on intravascular ultrasound-derived coronary atheroma burden. Circulation. 2008;117:2458-2466. 4. Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JG, Cornel JH, et al; CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007;357:2248-2261. 5. Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al; AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395-1407. 6. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005;366:1545-53. 7. CIBIS II investigators. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9-13. Competing interests: None declared |
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Malvinder S. Parmar, Associate Professor, Northern Ontario School of Medicine Timmins & District Hospital, Timmins, ON, Canada P4N 8P2
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The risk of cardiovascular (CV) events and death increases as serum creatinine increases1 or glomerular filtration rate (GFR) declines2 but this relationship is exponential as GFR declines <45 ml/min/1.73 m2. Patients with chronic kidney disease (CKD) and cardiovascular disease (CVD) often have common cardiovascular (CV) risk factors during early stages of CKD (stages 1, 2 & 3a) and the CV risk is similar unless proteinuria is present3. The non-traditional risk factors – such as, inflammation, anemia and calcium phosphate metabolism, contribute to CVD especially at advanced stages of CKD (stage 3b, 4 & 5), especially when the glomerular filtration rate (GFR) is <45 ml/min/1.73m2. In the Women’s Health Study4, off the 27,939 women, 4.7% (1315) women had a GFR of <60 ml/min/1.73m2. Of these 84 women had any CV event and 60 women died with 21 from CVD and 39 from non-CVD. Although total number of women with GFR of <40 ml/min/1.73m2 is not given but 67 of the 84 women with CV events had a GFR of <40 ml/min/1.73m2 and authors claim that the small number of women in this category limited the interpretation. However, it appears that most of the CV events occurred in women with GFR of <40 ml/min/1.73m2, than what authors claim to be in patients with GFR of <60 ml/min/1.73m2. I am not clear why authors selected a GFR of <40 ml/min/1.73m2 and NOT GFR of <45 ml/min/1.73m2, that has recently been categorized to be a separate category5 because of a small proportion of patients with CKD with increased risk of CKD progression, complications and risk of CVD, compared to stage 3a CKD (GFR 46-60 ml/min/1.73m2) that is more prevalent6 than stages 3b, 4 and 5 combined and majority of this stage patients are NOT at increased risk of CVD compared to general population3, so that limited resources be used effectively in real high-risk patients. However, Kurth et al4, combined stage 3a (apples) and stage 3b, 4 &5 (oranges) in their analyses and no doubt accordingly concluded that “GFR of <60 ml/min/1.73m2 in this cohort of women was associated with increased risk of CVD death” or simply that the “apples are sour!” There are large numbers of patients in stage 3a CKD compared to stages 3b, 4 and 5 combined and these two groups are different and the later group is at increased risk for CV disease and events and It is important to differentiate these two groups of CKD patients to effectively utilize limited resources. References: 1. Shulman NB, Ford CE, Hall WD, Blaufox MD, Simon D, Langford HG, Schneider KA. Prognostic value of serum creatinine and effect of treatment of hypertension on renal function. Results from the hypertension detection and follow-up program. The Hypertension Detection and Follow-up Program Cooperative Group. Hypertension. 1989 May;13(5 Suppl):I80-93. 2. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23; 351(13):1296-305. 3. Brantsma AH, Bakker SJL, Hillege HL, de Zeeuw D, de Jong PE, Gansvoort RT for the PREVEND study. Cardiovascular and renal outcomes in subjects with K/DOQI stage 1-3 chronic kidney disease: the importance of urinary albumin excretion. Nephrol Dial Transplant 2008; 23:3851-58. 4. Kurth T, de jong PE, Cook NR, Buring JE, Ridker PM. Kidney function and risk of cardiovascular disease and mortality in women: a prospective cohort study. BMJ 2009;338:b2392 5. Crowe E, Halpin D, Stevens P, on behalf of the guideline development group. Early identification and management of chronic kidney disease: summary of NICE guidance. BMJ 2008; 337:a1530 6. Imai E, Horio M, Yamagata K, Eseki K, Hara S, Ura N, Kiyohara Y, Makino H, Hishida A, Matsuo S. Slower decline of glomerular filtration rate in the Japanese General Population: A longitudinal 10-year Follow-up study. Hypertn Res 2008; 31(3):433-41. Competing interests: None declared |
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John A. Lee, Retired consultant in public health 1 Lugg View Close, Hereford HR1 1JF
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In the editorial (1) on the paper by Kurth et al (2) relating kidney function to cardiovascular disease risk and mortality in women, the authors suggest that more accurate measures of kidney function are needed than serum creatinine and estimates of glomerular filtration rate. One such measure might be that of the kidney endocrine function , notably the renin-angiotensin-aldosterone system, (a branch of the autonomic nervous system), which responds to a reduction in sodium concentration in the blood and leads to increased sodium absorption by the kidney and raised blood pressure. This would give an indication of the extent of cardiovascular system damage, particularly hypertension, so blood pressure wold be another measure. The paper (2) showed that there was an increased risk of cardiovascular disease death among women with impaired kiney function . Impaired kidney function can cause hypertension and cardiovascular disease while hypertension and other factors such as diabetes which predispose to cardiovascular disease , can in turn result in impaired kidney function . References. 1. D. E. Weiner and D, E. Rifkin. Kidney function and the risk of cardiovascular disease. (Editorial) BMJ. 2009;338:b1307 (4 July). 2. T.Kurth, P.E.de Jong, J. E. Buring and P.M. Ridker. Kidney function and risk of cardiovascular disease and mortality in women. : a prospective cohort study. BMJ 2009;338:b2392.(4July). Competing interests: None declared |
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