Displaying 1-10 letters out of 622 published
The possible impact of lack of ethnic and geographical diversity on the association of MTHFR mutations, homocysteine levels and heart disease outcomes
Methylenetetrahydrofolate reductase (MTHFR) plays an important role in conversion of homocysteine to methionine by catalyzing the production of 5-methyl tetrahydrofolate hence effectively decreasing plasma homocysteine levels. The MTHFR 677C>T nonsynonymous single nucleotide polymorphism (SNP) leads to a substitution of Valine for Alanine and results in the formation of a thermolabile variant of the enzyme with decreased basal enzymatic activity (1) resulting in increased homocysteine levels. The minor allele (T) of this SNP described in the study by Mehling at al was found to be associated with increased plasma homocysteine levels however the ancestral allele (C) was associated with an increased risk for coronary artery disease (CAD)(2). This finding is counter-intuitive and contrary to a large meta-analysis performed by Klerk et al involving a total of 11,162 cases and 12,758 controls that found that carriers of the minor allele T for this SNP had higher homocysteine levels and 16% higher risk of CAD (3). The increased risk for CAD in the TT genotype was related to lower folate concentrations.
The limitations of the study by Mehling et al are the failure to replicate their original findings in the INTERGENE cohort and a failure to measure folate levels. The study by Klerk et al did not find an increased risk for CAD in the minor allele carriers who had high folate concentrations. Another important limitation of this and other such studies due to the homogeneous European population studied is not to account for the racial diversity that exists with the MTHFR 677C>T genotype. The TT genotype is common in Mexico (32%), northern China (20%) and newborns of American Hispanic Ancestry (18%) as compared to a prevalence of 7% in the Swedish population studied by Mehling et al which could have accounted for the negative findings (4). Despite the higher prevalence of this SNP in these populations, studies examining the association of this genotype with homocysteine levels and CAD risk in these populations are scarce. The impact of such studies if performed in these countries or ethnic populations could potentially be far reaching by allowing assessment of preventive measures such as folate replacement on vascular and other complications associated with higher homocysteine levels in subjects carrying the susceptible TT genotype.
References (1)Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Denheijer M, Kluijtmans LAJ, Vandenheuvel LP, Rozen R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111-113
(2)K Mehlig, K Leander, U de Faire, F Nyberg, C Berg, A Rosengren, L Bj?rck, H Zetterberg, K Blennow, G Tognon, K Tor?n, E Strandhagen, L Lissner, and D Thelle The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism. Heart 2013;99:1761-1765
(3)Klerk, M., Verhoef, P., Clarke, R., Blom, H. J., Kok, F. J., Schouten, E. G., MTHFR Studies Collaboration Group. MTHFR 677C-T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288: 2023-2031
(4)Wilcken, B., Bamforth, F., Li, Z., Zhu, H., Ritvanen, A., Renlund, M., Stoll, C., Alembik, Y., Dott, B., Czeizel, A. E., Gelman-Kohan, Z., Scarano, G., and 19 others. Geographical and ethnic variation of the 677C- T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J. Med. Genet. 2003;40: 619-625
Conflict of Interest:
Re:Re:Use SMART risk score to correct under- and overtreatment.
As was pointed out by dr. Thomas and dr. Pleumeekers in personal communication, we have to admit that the case of a 70-year old patient with a 15% 10-year risk is not unthinkable. For example, a patient with the following characteristics has a predicted 15% 10-year risk for recurrent cardiovascular events: male 70 years, no smoker, systolic blood pressure 130 mmHg, diabetes mellitus no, CAD yes, CVD no, AAA no, PAD no, 11 years since first diagnosis, HDL cholesterol 1,33 mmol/L, total cholesterol 4,7 mmol/L, eGFR 91 mL/min and hs-CRP 0,2 mg/dL. We do appreciate the effort of these commentators to highlight potential therapeutic implications that such a low predicted risk might have, but remain unsure about discontinuing statins and other preventive medication on the basis of SMART risk score predictions given the other two reasons described.
Conflict of Interest:
Re:QRISK2 validation by ethnic group
We thank Professor Hippisley-Cox and colleagues for their comments on our paper. We agree that our study has limitations, but consider that we have stated these clearly within the manuscript. We believe that, notwithstanding these limitations, we bring new information regarding the performance of these widely used cardiovascular risk scores in three British ethnic groups. Importantly, these analyses were conducted independently of the authors of QRISK2 and Framingham risk scores and we report ethnicity-specific findings. Our take-home messages are that these risk scores performed differently and only modestly in the SABRE cohort in identifying individuals at high risk who would later go on to suffer events (particularly in South Asian women and in African Caribbean men and women). We suggest that further independent validation in other multi- ethnic datasets would be helpful.
With regards to specific comments, our responses are below: We agree that numbers of events were few in women, and indeed in African Caribbeans of both sexes - for this reason we urged caution in interpretation of the findings in these groups under 'Strengths and limitations'. The SABRE cohort is preponderantly male due to its initial objectives and in men there were 387 events (as stated). We show ethnicity specific % risk in men and women in figure 1, from which numbers of events can be estimated. For information, there were 173, 189 and 25 events in European, South Asian and African Caribbean men, respectively.
With regard to definition of outcome, we attempted to mirror the definition used in the derivation of QRISK2(1). We included participants who underwent coronary revascularisation procedures as having incident coronary heart disease (CHD), because such patients are most likely to be recorded as having CHD according to one of the nationally agreed Read codes used in the quality and outcomes framework for general practice (as reported in the methods for derivation of QRISK2)(1). Space limitations prevented us from reporting numbers of events recorded from different sources and we did not have complete data from all three sources for all participants. In summary, 302 events (65%) were derived from general practice record review(n=219) or death certificates(n=83). A further 31 events were identified solely through participant recall and the remaining 123 events were identified from Hospital Episode Statistics(HES). Inter-reporter agreement for GP record review and participant recall was excellent (kappa=0.79). For the 1308 participants where we could compare events reported from all three sources, the kappa value indicated good agreement( 0.63). We should point out that admission practices have changed and that early HES records (before 1997) are generally regarded as less than complete than more recent records, hence it is highly likely that HES records for the 10 year period following our baseline (1988-91) underestimate rather than overestimate events for that period. Sensitivity analyses restricted to events identified solely by GP record review produced similar findings to those reported in the paper.
We agree that South Asians and African Caribbeans in our cohort are all first generation migrants and we specifically state that 'our findings may not be generalisable to future generations in each ethnic minority group', although the extent to which UK ethnic differences in CHD risk are changing across generations remains to be established.
We agree also that a number of data items were missing for our calculation of the QRISK2 scores, and we noted this limitation under 'strengths and limitations' . We note that the derivation and validation datasets for QRISK and QRISK2 contained less than 1% with rheumatoid arthritis and less than 0.17% with chronic kidney disease; in addition less than 0.6% had atrial fibrillation(ref). Such small amounts of missing data are unlikely to impact on our findings. We agree that data on family history were collected only at follow-up and that this is a key shortcoming, however, as reported, sensitivity analyses which included history of parental CVD at age less than 60 years in a subset(n=1854) did not improve calibration or classification, although it did improve discrimination in African Caribbeans (but not in Europeans or South Asians).
It is a strength of our study that we had complete data for 3674 participants(94% of those followed-up) for key baseline risk factors: blood lipids, smoking , blood pressure and body mass index and that ethnicity in all participants was defined based on self-assignment and country of birth of parents. In contrast, the main analyses for derivation of QRISK2, of necessity, used multiple imputation to replace missing values for systolic blood pressure, cholesterol/HDL ratio (available in <35%), smoking status, and body mass index. (1)
We thank Hippisley-Cox and colleagues for drawing attention to the 2013 online QRISK2 update; we agree that the increase in patient self- assigned ethnicity (now at 50%) will have improved the accuracy of this tool. Nevertheless, given the importance of accurate risk scoring, as recently highlighted by the critical responses to the recently released AHA guidelines(2), further validation of the QRISK2 update as it applies to ethnic groups, would seem warranted.
Therese Tillin, Alun D Hughes, Peter Whincup, Jamil Mayet, Naveed Sattar, Paul M McKeigue, Nish Chaturvedi
1. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, Brindle P: Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ 336:1475-1482, 2008
2. Ridker PM, Cook NR: New American guidelines for prevention of cardiovascular disease. Lancet 2013, published online 20/11/2013, doi:10.1016/S0140-6736(13)62388-0
Conflict of Interest:
QRISK2 validation by ethnic group
Tillin et al recently reported a cohort study comparing the performance of QRISK2 and Framingham in the Southall and Brent cohort in London. We have a number of comments on the study and the interpretation of results.
1. Number of events : The main problem with the paper, is that numbers are very small and given the resulting wide confidence intervals the authors have overstated their findings. There is no information on how many patients had the outcome in the different ethnic groups but there were only 78 events in women overall, so the sub-group numbers are likely to be extremely small. The fact that the authors reported little difference between the two scores is likely to be due to the very wide confidence intervals and small numbers.
2. Definition of outcome: We suspect the under-prediction of QRISK2 is due to their broader definition of the cardiovascular disease outcome which includes HES data and patient reported outcomes. They have also included revascularization procedures. They do not report how many events were from different sources or an assessment of how they validated the retrospective self-reported events. From 2014 - QRISK2 annual updates include linked hospital episode data which increases ascertainment of events by approximately 10%.
3. Characteristics of the cohort: The SABRE cohort largely comprised first generation migrants with baseline measurements made over 20 years ago. The QResearch database, which is used to develop QRISK2, includes a nationally representative group of diverse ethnic groups many of whom will be second or third generation at lower risk than first generation migrants.
4. Calculation of the QRISK2 score: A number of the data items needed to calculate a QRISK2 score were missing in their dataset. There was no baseline information on rheumatoid arthritis, family history of premature IHD, chronic kidney disease or atrial fibrillation. Absence of this information is likely to have lowered discrimination. Similarly, the cohort consisted of patients aged 40-69 which will have lowered discrimination compared with evaluation of QRISK2 across the wider age range of 30-84 years.
5. Reporting of performance by ethnic group. The authors mention that the QRISK2 score has been validated in internal and external datasets but that the performance of QRISK2 has not been reported separately by ethnic group. We would like to draw readers attention to the QRISK-2013 update information which was published online in April 2013 and which includes validation statistics separately for each ethnic group. The tables at http://www.qrisk.org/QRISK2-2013-Annual-Update-Information.pdf demonstrates good performance in all ethnic groups.
References 1. Tillin T, Hughes AD, Whincup P, et al. Ethnicity and prediction of cardiovascular disease: performance of QRISK2 and Framingham scores in a UK tri-ethnic prospective cohort study (SABRE--Southall And Brent REvisited). Heart 2013 doi: 10.1136/heartjnl-2013-304474[published Online First: Epub Date]|. 2. Hippisley-Cox J, Coupland C. QRISK2-2013 Annual Update Information, 2013:5. http://www.qrisk.org/QRISK2-2013-Annual-Update-Information.pdf
Conflict of Interest:
JR chaired, and PB was a member of, the NICE guideline development group on cardiovascular risk assessment"The modification of blood lipids for the primary and secondary prevention of cardiovascular disease."JHC is codirector of QRESEARCH, a not for profit organisation that is a joint partnership between the University of Nottingham and EMIS (leading supplier of information technology for 60% of UK general practices).JHC is also director of clinrisk which supplies open and closed source software to implement QRISK2.
Potential weakness of the metanalysis
I have read with interest your metanalysis on effects of antihypertensive treatment in patients over 65 years of age, and I would like to point to an issue quite relevant on my view. I have checked some of the trials included because I doubted if it was possible to the authors to separate participants with more than 65 years from younger, excluding the latter from the analysis. For instance, in the ALLHAT study the authors have been able to give data from participants older than 65 years because the original paper offers that information. But looking now at the INVEST trial, the bigger of this metanalysis excluding ALLHAT, the authors have included all the 22576 participants. The design of INVEST included people older than 50 years and the report explains that most of them (15053) are under 70 years, so we can expect to have many of them under 65 years. This situation can easily have influence in the outcomes mesured and it should have been managed properly. If we are going to speak about older people, just data from older people should have been collected. Or, if it were not possible to get separate data from some trials, I think it would have been better to exclude them.
Conflict of Interest:
RESOLVE could not verify the VERIFY study
'The first step of scientific progress is both accepted knowledge and continual, instantaneous willingness to admit that what we believed true earlier was wrong and needing replacement...' Lance Gould 
We thank Fan, Qi, He, Yang and Pijls for their continued interest in our work and physiology as a whole. Science thrives on experiments repeatable in independent hands. Dogma, on the other hand, discourages independent thought and when results are unexpected, an enormous scientific hiatus follows. Leaders unwilling to change, may feel obliged to further entrench into cherished concepts but this only makes the inevitable paradigm shift more unpleasant.
Yang et al correctly point out the importance of RESOLVE, an international collaboration that was necessary to resolve important questions raised by the VERIFY study. Although the final results of RESOLVE were to conclude that in independent hands the findings were similar to results by the ADVISE investigators [4-6], perhaps the most important message may have been missed. VERIFY, when re-analysed independently using the validated iFR algorithms, was not as originally presented and the findings of Berry et al. could not be substantiated. Now VERIFY, hailed as the death knell of iFR, stands alone, conflicting with every other iFR-FFR study in the field. How could this have occurred?
It is now evident that in a fervour of excitement, serious oversights and amnesiac errors seem to have arisen.
First, the VERIFY authors paid little attention to the accuracy of their iFR wave-free period and instead chose to define diastole as including a part of systole (clearly visible in Figure 1 of the VERIFY manuscript). Whilst superficially appearing to be only a minor physiological transgression, the fundamental principles of iFR state that resistance is only stable and minimised over the cardiac cycle where waves are absent - i.e. the wave-free period.
Second, unique patient numbers appear overstated, and misrepresented in the manuscript. This means that the same patients were included twice in the manuscript, potential seriously skewing the dataset.
Third, and perhaps most worrying, Berry declared no conflict of interest when presenting VERIFY at ACC (2012) but had in fact broken the embargo by presenting first to stock market analysts.
Together all of these factors led to the VERIFY study's reported accuracy of between 49-60% being revised to 79.4% when independently re-analysed using the validated algorithms in RESOLVE. We urge Yang et al. to interpret the VERIFY dataset, and any other dataset which includes its data, with extreme caution.
iFR and FFR are both indices of physiological stenosis severity. Both use pressure wire technology, but iFR as a resting measure does not require the administration of vasodilators such as adenosine. iFR can be measured at an instant at any time during the wave-free period, hence its name. The wave-free period provides a form of natural hyperaemia, present in every beat. Adding external sources of vasodilatation will lower iFR value, but this does not alter the diagnostic accuracy as cut-offs also become lower.[9,10] Despite concerns that resting states are not possible in the catheter laboratory, ample evidence suggests otherwise.
Accordingly, post-PCI assessment is possible and iFR is a dynamic measure of stenosis severity . Whilst lesion classification disagreements may occur, all the evidence to date indicates that both measures are equally effective in agreeing with independent third measures of ischaemia.[7,9,13]. Whether differences between these indices are clinically important will be established in iFR clinical outcome studies such as FLAIR and SWEDEHEART.
1 Gould KL, Johnson NP. Imaging in aortic stenosis--let the data talk. JACC Cardiovasc Imaging 2012;5:190-2. doi:10.1016/j.jcmg.2011.10.005
2 Allen Jeremias, Akiko Maehara, Philippe Genereux, et al. Multicenter Core Laboratory Comparison of the Instantaneous Wave-Free Ratio and Resting Pd/Pa with Fractional Flow Reserve: The RESOLVE Study. J Am Coll Cardiol 2013;In Press.
3 Berry C, van't Veer M, Witt N, et al. VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice): A Multicenter Study in Consecutive Patients. J Am Coll Cardiol 2013;61:1421-7. doi:10.1016/j.jacc.2012.09.065
4 Sen S, Escaned J, Malik IS, et al. Development and Validation of a New Adenosine-Independent Index of Stenosis Severity From Coronary Wave-Intensity Analysis: Results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) Study. J Am Coll Cardiol 2012;59:1392-402. doi:10.1016/j.jacc.2011.11.003
5 Petraco R, Escaned J, Sen S, et al. Classification performance of instantaneous wave-free ratio (iFR) and fractional flow reserve in a clinical population of intermediate coronary stenoses: results of the ADVISE registry. EuroIntervention 2013;9:91-101. doi:10.4244/EIJV9I1A14
6 Petraco R, Park JJ, Sen S, et al. Hybrid iFR-FFR decision-making strategy: implications for enhancing universal adoption of physiology-guided coronary revascularisation. EuroIntervention J Eur Collab Work Group Interv Cardiol Eur Soc Cardiol 2013;8:1157-65. doi:10.4244/EIJV8I10A179
7 Sen S, Escaned J, Petraco R, et al. Reply to Letter to the Editor: iFR, Science, Size and Serendipity - Can lightning strike twice? J Am Coll Cardiol Published Online First: 6 June 2013. doi:10.1016/j.jacc.2013.05.036
8 Johnson NP, Kirkeeide RL, Asrress KN, et al. Does the instantaneous wave-free ratio approximate the fractional flow reserve? J Am Coll Cardiol 2013;61:1428-35. doi:10.1016/j.jacc.2012.09.064
9 Sen S, Asrress KN, Nijjer S, et al. Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study). J Am Coll Cardiol 2013;61:1409-20. doi:10.1016/j.jacc.2013.01.034
10 Sen S, Nijjer S, Petraco R, et al. Letter to the Editor: Instantaneous wave-free (iFR): Numerically different, but diagnostically superior to FFR? Is lower always better? J Am Coll Cardiol Published Online First: 20 May 2013. doi:10.1016/j.jacc.2013.03.076
11 Wilson RF, White CW. Intracoronary papaverine: an ideal coronary vasodilator for studies of the coronary circulation in conscious humans. Circulation 1986;73:444-51.
12 Nijjer SS, Sen S, Petraco R, et al. Improvement in coronary haemodynamics after percutaneous coronary intervention: assessment using instantaneous wave-free ratio. Heart Published Online First: 18 September 2013. doi:10.1136/heartjnl-2013-304387
13 Van de Hoef T, Meuwissen M, Sen S, et al. Basal Stenosis Resistance Index And Instantaneous Wave-Free Ratio Have The Same Diagnostic Performance As Fractional Flow Reserve To Detect Myocardial Ischemia Using Myocardial Perfusion Imaging. J Am Coll Cardiol 2013;61. doi:10.1016/S0735-1097(13)61756-8
Conflict of Interest:
Dr Davies holds intellectual property pertaining the iFR technology
Re:Have I missed something here?
Peri-ablation dabigatran in atrial fibrillation: not only about thromboembolism.
We have read with interest the letter by Ward (1) about our recent publication (2). The author raised an important point: why should dabigatran be interrupted during a procedure known to be associated with risk of thromboembolic events? Ward also noted that our meta-analysis did not include any study with uninterrupted dabigatran. While it is true that left atrial ablation procedures are associated with risk of thromboembolism, they also carry risk of potentially life threatening bleeding.
Given the low thromboembolism and bleeding rates with uninterrupted warfarin, it would appear reasonable to consider the use of uninterrupted dabigatran. Factors that have deterred its use include lack of an antidote and the overall lesser clinical experience with the medication in comparison to warfarin. An increased requirement for intra-procedural heparin with peri-ablation dabigatran (3), and prior report of more bleeding with peri-ablation dabigatran (4) use may have also limited use of this approach. Importantly, most of the available studies have examined interrupted dabigatran versus warfarin (often uninterrupted), and the results of several meta-analyses (5,6,7) have shown a comparable efficacy and safety profile for the two anticoagulants. We limited our analysis to studies that compared interrupted dabigatran with warfarin therapy to minimize in between studies heterogeneity that would impact interpretation and applicability the results. If more data become available on uninterrupted dabigatran use, it could become a more widely accepted approach if safety is proven.
1. Ward D. Have I missed something here? . Heart.2013. (In press)
2. Bin Abdulhak AA, Khan AR, Tleyjeh IM, et al. Dabigatran in the setting of catheter ablation of atrial fibrillation: the road ahead. Heart Published Online First: [10/14/2013] doi: 10.1136/heartjnl-2013-304989
3. Konduru SV, Cheema AA, Jones P,et al. Differences in intra- procedural ACTs with standardized heparin dosing during catheter ablation for atrial fibrillation in patients treated with dabigatran vs. patients on uninterrupted warfarin. J Interv Card Electrophysiol 2012; 35: 277 - 84.
4. Lakkireddy D,Reddy YM,Di Biase L,et al.Feasibility and safety of dabigatran versus warfarin for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol 2012;59:1168-74.
5. Bin Abdulhak AA, Khan AR, Tleyjeh IM, et al.Safety and efficacy of interrupted dabigatran for peri-procedural anticoagulation in catheter ablation of atrial fibrillation: a systematic review and meta- analysis.Europace (2013) 15 (10): 1412-1420
6. Providencia R, Albenque J-P, Combes S, et al. Safety and efficacy of dabigatran versus warfarin in patients undergoing catheter ablation of atrial fibrillation: a systematic review and meta-analysis. Heart Published Online First: 22 July 2013 doi: 10.1136/heartjnl-2013- 304386.
7. Hohnloser S, Camm A. Safety and efficacy of dabigatran etexilate during catheter ablation of atrial fibrillation: a meta-analysis of the literature. Europace 2013;15(10):1407-11.
Conflict of Interest:
Have I missed something here?
Am I missing something here? It is generally accepted that the omission of a single dose of dabigatran, which has a short elimination half-life, may place a patient at risk of thromboembolism. So why should atrial fibrillation ablation be any different especially when one is potentially stimulating thrombus formation in the left atrium during and possibly after the procedure? Why not continue the drug through the procedure as reported by Maddox et al (1)? Is it not completely illogical to do otherwise? More trials of this approach are needed. Abdulhak's meta- analysis (his reference 2) did not include any studies of uninterrupted dabigatran treatment.
1.Maddox W, Kay GN, Yamada T et al. Dabigatran versus warfarin for uninterrupted oral anticoagulation during atrial fibrillation ablation. Journal of Cardiac Electrophysiology 2013;24:861-865
Conflict of Interest:
Instantaneous Wave-free Ratio: a Word of Caution or Reliable Parameter?
TO THE EDITOR: We take great interest in the paper1 by Nijjer et al. with regard to instantaneous wave-free ratio (iFR) assessing improvement in coronary haemodynamics after percutaneous coronary intervention (PCI). However, we have some concerns about the invasive, pressure-only index, iFR.
iFR, a novel resting index without hyperemia, is calculated over five heartbeats as the ratio of distal to proximal coronary pressures during the diastolic. The assumption is that the resistance during a particular part of diastole will be as low as the average resistance during the complete heart cycle in hyperemia and not be influenced by adenosine infusion.2 Nevertheless, assumption is assumption, whilst numerical equation makes sense. Fluid-dynamics equation elucidates that iFR is able to predict the severity of stenosis (e.g. a 70% long LAD stenosis) only when friction is the predominant cause of energy loss within the stenosis. 2 That is to say, a short 50% left main stenosis, in which separation and turbulent flow are responsible for the energy loss, creates a negligible resting gradient with an extremely large hyperemic gradient. In the recent Resolve registry3, a poor correlation was found between iFR and fractional flow reserve (FFR). Only if iFR was <0.82 (as in 24% of the 1,539 patients) could hyperemia be omitted to achieve a 95% certainty of making the correct decision whether or not to revascularize. So our question raised again, is iFR equivalent to FFR?4 It is not even instantaneously measured as the name suggests or totally independent of pharmacological vasodilatation, because it is calculated as an average value and strongly influenced by hyperemia.2 We really appreciate this prospective observational study applying iFR to assess improvement in coronary haemodynamics after PCI. It found that the change in iFR after intervention (0.20?0.21) was similar to ?FFR 0.22?0.15 (p=0.25). Surely, based on the data the study presented, iFR might be used to objectively document improvement in coronary haemodynamics following PCI in a similar manner to FFR.1 However, iFR may have a highly variable measurement in clinical practice, as it is almost unachievable to create a true resting condition and obscure to determine what extent some hyperemia is present.
Reference 1. Nijjer SS, et al. Improvement in coronary haemodynamics after percutaneous coronary intervention: Assessment using instantaneous wave- free ratio. Heart. 2013; 2. Pijls NH. Fractional flow reserve to guide coronary revascularization. Circ J. 2013; 77: 561-569. 3. A. J. Resolve: A multicenter study to evaluating the diagnostic accuracy of ifr compared to ffr. J Am Coll Cardiol. 2013; 4. Fan GX and Xu YW. Is the instantaneous wave-free ratio equivalent to fractional flow reserve? J Am Coll Cardiol. 2013; 62: 943.
Conflict of Interest:
Re:Use SMART risk score to correct under- and overtreatment.
Complex drug regimens and overtreatment in elderly persons are important medical issues. Less stringent treatment for example of blood pressure, may be allowed or is even advisable in the elderly, especially in the presence of coexisting morbidities, adverse side effects of medication or impaired mobility. Still, the SMART risk score will not help determine which patients can safely withdraw treatment for several reasons. First, SMART risk score predictions are based on current practice. This means: assuming optimal medical treatment according to current standards, including antiplatelet therapy, lipid-lowering and blood pressure-lowering medication when indicated. Second, the SMART study was not a trial. This means that the counterfactual situation, withdrawal of treatment, is not observed. The magnitude of the risk increase and potential rebound effects after withdrawal of treatment are, therefore, unknown. Third, the patient described above is non-existent. According to the SMART risk score, a 70-year old male with a history of a PCI 11 years earlier has a minimum risk of 20%, assuming no other risk factors are present. Thus, at this age, all patients will be at high risk, some only more than others. In conclusion, we advise using the SMART risk score only for identifying those patients at highest risk for recurrent vascular events and to consider intensifying treatment, but not for making decisions about treatment withdrawal. We agree with our colleagues that stopping preventive treatment is an underexposed activity in clinical practice and need proper scientific evaluation. Assessing the effects of stopping medication in prospective randomized clinical trials would deliver answers to these burning questions.
Conflict of Interest:
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