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Copyright Medinews (Cardiology) Limited Reproduction Prohibited
Copyright Medinews (Cardiology) Limited Reproduction Prohibited
The interest in the increasing overlap between cardiac and renal disease was shown by a wel -attended meeting, ‘The failing heart and kidney’, organised by the Cardiorenal rohibited F C
orum. Oover 1p00 neyphrolrogiy angd cardhiologty co nsulM
tants/train eees, sdpecialiisn
t nurse es FORUM
and other health personnel with a special interest in this field attended the meeting at the British Academy, London, on 11 July 2008. Cause or effect
The evidence is not as clear in heart failure eproduction P
with preserved ejection fraction, and the e meeting s a
Dr Mike Schacter (Senior Lecturer, Department question arises: what are we treating? Some with Dr Alan Jardine (Consultant Nephrolol
f Clinica y
s Hospital, it
tudies hd
ited R Western Infirmary, Glasgow) providing an
London) went on to explore in detail the role suspected heart failure and preserved left terestin e
miologicral oo
of neurohormonal activation in heart failure ventricular systolic function suffer from diastolic cardiorenal disease. The increasing prevale u
nce and a systematic overview of the natriuretic heart failure or from misdiagnosis. While there cpeptidet/kiniion
re is not r
is unequi i
al evidenc te
e in heart f d
hand-in-hand with a growing cardiovascular pump failure, but a systemic syndrome with RAAS inhibition in the presence of impaired left ventricular systolic function, this is currently progressive renal disease are known to have metabolic responses. Al drug interventions that much less convincing in heart failure with have improved outcomes in heart failure have Cardiology) L
preserved left ventricular systolic function.
pattern of outcomes and the relationship interacted with these neurohumoral responses. s ( with risk factors are somewhat different from Activation of the renin–angiotensin system
Control ing risk factors
the general population. CVD accounts for (RAS) results in structural (loss of proximal 50% of mortality in endstage renal disease convoluted tubules [PCT] and fibrosis) and Dr Philip Kalra (Consultant Nephrologist, edinew (ESRD). While there have been several
functional (reduction of PCT flow/oxidative Salford Royal Hospital, Salford) proceeded to tudies as osessinp
g the im ypact orf rediucged stress) changes leading to hypoxia of the demystify the kidney and the classifications of
estimated glomerular filtration rate (eGFR) kidney and subsequent ESRD as a result of CKD currently available. The prevalence of CVD on cardiovascular outcome, the key questio h
in CKD dramatical y worsens once the eGFR fal s below 60 ml/minute. Studies have clearly Dr Iain Squire (Senior Lecturer, Cardiovascular shown that the rates of death and cardiovascular , Leicester) sh e
her ligh i
Copyright M Pr(eviC
ous view a
d that th ie eo
death rose with the decline of renal function, importance of renin–angiotensin–aldosterone of common risk factors like hypertension, with cardiovascular mortality rates being much system (RAAS) blockade in heart failure by smoking and hyperlipidaemia explained the higher among dialysis patients. Left ventricular separately analysing their roles in reduced close association between CVD and CKD, bu o
hypertrophy, calcification of coronary arteries, raction. i
ost of the ited
idence n e
nts towrardo
uraemic arteriopathy/atherosclerosis were all evidence base is undoubtedly in heart failure relationship between the two entities. ESRD earmarked as contributing factors. The most with reduced ejection fraction. Data from several leads to hyperlipidaemia, inflammation and significant risk factors associated with the long-term randomised-control ed trials (SAVE, malnutrition, all of which may contribute to progression of CKD include hypertension and equivoca r
atheromatous coronary artery disease. ESRD benefit with the use of angiotensin-converting proteinuria, and as such, treatment should be in itself also causes uraemic cardiomyopathy, enzyme (ACE) inhibitor therapy resulting in left ventricular hypertrophy, myocardial reduction in mortality and re-admission, as well Meta-analysis of several randomised-control ed as re-infarction. The wealth of evidence led to trials have highlighted the relationship between the National Institute for Health and Clinical systolic blood pressure and increased risk of association between chronic heart failure and Excel ence (NICE) spel ing out in its heart failure CKD, with evidence of slower decline in renal CKD. Neurohormonal activation secondary to guidelines that al patients with heart failure function with lower blood pressure goals. The diminished renal perfusion and subsequent due to left ventricular dysfunction should be drugs of choice for blood pressure control in impaired function resulting in the entity of considered for treatment with an ACE inhibitor, CKD would be ACE inhibitors, angiotensin cardiorenal syndrome in heart failure was with emphasis on the need to achieve optimal receptor blockers (ARBs) and selective renin inhibitors, like aliskiren, aiming to achieve 290 | The British Journal of Cardiology | November/December 2008 | Volume 15 Issue 6
Copyright Medinews (Cardiology) Limited Reproduction Prohibited
Copyright Medinews (Cardiology) Limited Reproduction Prohibited
target blood pressures of 125/75 mmHg in
patients with proteinuria and 130/80 mmHg
in al others. In patients with diabetes,
suboptimal blood pressure control results in
GFR loss of 8–16 ml/min/year and with tight
blood pressure control, this fal s to as little as
1–2 ml/min/year. (Age-related decline in GFR
in a normal individual is 1 ml/min/1.73 m2 after
30 C
Dr Kalra em o
phasise p
t is co rmmoig
see deterioration in renal function with RAAS blockade in patients with congestive heart hiStockphott Medinews
failu (re, C
o 25% rincred
ase in icreo
atinine lis
acceptable. Higher values may be acceptable in patients with severe congestive cardiac The onset of microalbuminuria and proteinuria in patients with type 2 diabetes increases the risk failure. If significant changes occur, reducing ogof progyressio)n to e ndstLage renail dim
eproduction P
e diuretic d eose ap
nd repeartino
g bioche d
>10 suggests persistent microalbuminuria and Global risk reduction
>30 nephropathy. Once CKD stage 3 sets in, functional y significant atherosclerotic The keynote lecture delivered by Dr Kausik quired a r
nd ohibited
renovascular disease (ARVD). It was interesting Ray (BHF International Fel ow and Consultant to note that at Salford Royal Hospital, 51% Cardiologist at Addenbrooke’s Hospital) of 527 ARVD patients receiving or previously The progression of renal disease in type focused on the global risk reduction of CVD. 2 diabetes is accelerated by the onset of While cardiovascular mortality has declined in were intolerant, thus breaking the myth that the UK, with improved survival in myocardial Cardiology) L
microalbuminuria with the onset of proteinuria the presence of ARVD is a contraindication infarctions and acute coronary syndromes, marking a steep decline of renal function and the burden of coronary heart disease (CHD) is progression to ESRD. Cardiovascular mortality increasing. On a global scale, by 2020, CHD Diabetic nephropathy
correlates with the severity of microalbuminuria and stroke are projected to become the leading in type 2 diabetes. Preventing renal disease Dr Marc Eva ons (Cop
nsultan yt diabertoloigist,g
cause of death and disability worldwide, with in diabetes by tighter glycaemic control and mortality from CVD increasing to 20 mil ion. Atherosclerosis is believed to begin as early diabetic nephropathy, highlighting the need as in teenage years. Low-density lipoprotein for col aborative combined care of patients hmictrova sculM
ar end point e
is mucnh in e(LDLw
) increase s
young adulthood, and with age, high-density by d(iabC
etologist a
s and n rephrd
ologists i. To
macrovascular complications. The management lipoprotein (HDL) becomes less protective. chal enge of diabetes is ever rising with about one mil ion patients with diabetes still meticulous blood glucose control, regular The added protective effect of HDL seen in being undiagnosed national y and diabetic logy) Limited
Copyright M
measurement of renal function (eGFR), lifestyle women is lost after the age of 70. Even when hropath e
y contri p
rg to 50o% of nedw changes, aspirin, and tight blood pressure, as high-risk primary prevention patients are
dialysis patients. Managing diabetics costs treated, two thirds of events are still missed. the National Health Service (NHS) about £5
billion per annum (8–10% of total healthcare u
l bloo ion
l often roh
Dr Ray the i
roceeded t te
o explore e d
costs) and 80% of the costs are related to require combination therapy. However, the diabetes complications. Dr Evans highlighted strongest data for improving outcomes (both strategies available. Meta-analyses of intensive the superiority of albumin–creatinine ratio statin therapy studies and dyslipidaemia mortality and renal) are with RAS antagonists (ACR) over protein–creatinine ratio (PCR). trials all point towards the benefit of lowering and in particular ARBs. Dr Evans highlighted ACR is seen as the gold-standard testing for cholesterol with statins, irrespective of that in Irbesartan in Diabetic Nephropathy urinary albumin and although PCR measures total protein and is useful for patients with (IDNT) and Irbesartan in Type 2 Diabetics with Ongoing data analysis by Dr Ray highlights proteinuria, it is not accurate enough to Microalbuminuria (IRMA-2), treatment with that higher HDL is associated with a reduction determine microalbuminuria. ACR should be irbesartan was associated with a reduction measured annual y in diabetics, cut-offs being in primary end points independent of blood- strategies for increasing HDL and reducing >2.5 in males and >3.5 in females. An ACR triglycerides include smoking cessation, regular Volume 15 Issue 6 | November/December 2008 | The British Journal of Cardiology | 291
Copyright Medinews (Cardiology) Limited Reproduction Prohibited
aerobic exercise, weight reduction and optimal proposed the motion based on the similar heterogeneity of response, benefits seen diabetes control, as well as the use of drugs like statins, fibrates, niacin, metformin, etc.
drugs, as well as the absence of difference in suggest that the two drugs have different outcome in studies where both drugs were cholesterol/LDL is certainly applicable to blood used together. ACE inhibitors in addition to pressure as wel . The risk of CHD mortality preventing the conversion of angiotensin I to speakers, a final show of hands proved a tilt doubles with every 20 mmHg rise in blood II also prevent the breakdown of bradykinin in audience opinion and a clear win in favour rohibited pr
to inactive peptides. ARBs on the other hand essure a ot any apge. Datya frorm a nuimgber of
trials have suggested that perhaps the mode selectively block the AT receptors, leaving AT of lowering blood pressure is also important. unopposed. Studies have shown bradykinin informative and enlightening day was that NICE recommend ACE inhibitors for patients h
eft ventricul e
ertroph i
problem and it is, thus, the need of the hour cardiovascular effect, suggesting no added younger than 55 years and calcium channel that general practitioners, nephrologists, blockers/diuretics in those older than 55 or benefit by inhibiting the bradykinin breakdown eproduction P
diabetologists, cardiologists and whoever else Caribbea a
pathway. According to Dr Ferro, no significant may be involved in patient care, work in close monotherapy fails, a drug from the other g l
e mortalit i
r primary it
outcome was seen in the Valsartan in Acute ited R is added and many patients require al three
may vary, but the unifying factor remains drugs in combination. The keynote lecture ended Myocardial Infarction (VALIANT) trial (captopril, the predisposition to vascular disease and its t a multifa r
valsartan and the combination) or the Ongoing subsequent complications. By maintaining a the need of the hour in the drive to combat the cTelmisatrtanion
ation wit r
vigilant a i
roach and ote
ptimising t d
Ramipril Global Endpoint (ONTARGET) trial, hence ruling out superiority of either class ACE inhibitors versus ARBs
cardiovascular complications held at bay • of drug. While ARBs certainly cause less angioedema, in his opinion, that certainly was Conflict of interest
Cardiology) L The day’s session, punctuated by informative
not a strong enough reason to prevent them The meeting was supported by an unrestricted s ( discussions between talks and good audience
educational grant from Sanofi-Aventis and Bristol-Myers with the motion ‘ACE inhibitors and ARBs are interchangeable in cardiorenal disease’. Donah Zachariah,
edinew Dr Albert Ferro (Reader Cardiovascular
convincing counter argument on the grounds Cardiology Specialist Registrar,
that, in addition to there being an inter-patient Queen Alexandra Hospital, Portsmouth
NCE yright Medinews
Copyright M
ce) Limited
thors’ r r
Dear Sirs
I felt that ‘10 steps before you refer for hypertension’ was a good This is a well-made point and you are, of course, quite right. article but given that point 1 was “check that the measurement The picture was chosen for visual impact rather than as a is correct”, why on earth would you have a picture of an aneroid recommendation. Aneroid sphygmomanometers are only accurate sphygmomanometer on the front cover when these are known when new or after recalibration, which is recommended every six months. They rely on a coiled spring which loosens with each use. The authors do not recommend their routine use in practice. Yours faithfully
Terry McCormack
Peter Sever
Professor of Clinical Pharmacology and Therapeutics, Imperial Col ege London Francesco Cappuccio
Warwick Medical School, Coventry
292 | The British Journal of Cardiology | November/December 2008 | Volume 15 Issue 6



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