The interesting paper of Merz and Cheng did not mention iron as a
plausible non-hormonal factor, which might in part explain the sex
differences in cardiovascular aging [1].
Mounting evidence suggests that the metabolic derangements and
detrimental cardiovascular effects usually attributed to menopause
represent only a mere consequence of the older age of menopausal women,
rather than related to the loss of ov...
The interesting paper of Merz and Cheng did not mention iron as a
plausible non-hormonal factor, which might in part explain the sex
differences in cardiovascular aging [1].
Mounting evidence suggests that the metabolic derangements and
detrimental cardiovascular effects usually attributed to menopause
represent only a mere consequence of the older age of menopausal women,
rather than related to the loss of ovarian function. In fact, heart
protection by premenopausal levels of female hormones, that is the
oestrogen hypothesis, is not consistent with epidemiological findings that
premenopausal hysterectomy essentially cancels the protection even in
patients with preservation of functioning ovaries [2]. On the contrary,
these data [2] suggest that an intact uterus has an important role in the
protection of premenopausal women, and this is likely related to the
beneficial effect of iron depletion in menstruating women (i.e. the iron
hypothesis suggested since 1981 by Sullivan [3]).
A protective effect of iron depletion may be related to the decreased
availability of redox-active iron within atherosclerotic lesions. Serum
ferritin concentrations, commonly used as a surrogate for iron stores, are
significantly lower in premenopausal menstruating women (25-50 ng/mL)
compared to men (140-150 ng/mL) of similar age, but slowly increase after
menopause. Interestingly, average menstrual blood loss each year (780 mL)
approximates blood loss from donating approximately two 500 mL units of
whole blood [4]. It is noteworthy that phlebotomy of one unit of whole
blood twice a year among predominantly white middle-aged and elderly men
with peripheral arterial disease, resulted in a significant decrease in
overall mortality, myocardial infarction and stroke over a several year
period, compared to the control group not phlebotomized [4]. Not
surprisingly, during the trial, the average serum ferritin concentration
in the iron reduction group was approximately 60 ng/mL compared to 110
ng/mL in the control group [4]. On the contrary, it has become evident
that supplemental iron use among elderly woman may be significantly and
dose dependently associated with increased total mortality [5].
In conclusion, higher vascular wall iron, contained in macrophages,
might in part explain the sex difference in cardiovascular ageing.
Moreover, donating blood twice a year by men and possibly postmenopausal
women might decrease CVD morbidity and mortality. Furthermore, unnecessary
iron supplements should be avoided and iron fortification of our food
supply should be questioned. Finally, randomized trials of iron depletion
for the primary and secondary prevention of vascular disease need to be
done.
1. Merz AA, Cheng S. Sex differences in cardiovascular ageing. Heart
2016 Feb [Epub ahead of print].
2. Kannel WB, Levy D. Menopause, hormones, and cardiovascular
vulnerability in women. Arch Intern Med 2004;164:479-81.
3. Sullivan JL. Iron and the sex difference in heart disease risk. Lancet
1981;1:1293-4.
4. Zacharski LR, Shamayeva G, Chow BK. Effect of controlled reduction of
body iron stores on clinical outcomes in peripheral arterial disease. Am
Heart J 2011;162:949-957.e1.
5. Mursu J, Robien K, Harnack LJ. Dietary supplements and mortality rate
in older women: the Iowa Woman's Health Study. Arch Intern Med
2011;171:1625-1633.
We thank Dr. Goldstein for bringing to our attention the iron
hypothesis as a potential non-hormonal factor contributing to sex
differences in cardiovascular aging. We also find intriguing the
possibility that iron depletion in menstruating women may be cardio-
protective. We had previously been aware of the potential role of iron as
a byproduct of heme-oxygenase activity in mediating cardiometabolic
risk,[1] with a numb...
We thank Dr. Goldstein for bringing to our attention the iron
hypothesis as a potential non-hormonal factor contributing to sex
differences in cardiovascular aging. We also find intriguing the
possibility that iron depletion in menstruating women may be cardio-
protective. We had previously been aware of the potential role of iron as
a byproduct of heme-oxygenase activity in mediating cardiometabolic
risk,[1] with a number of community studies having reported equivocal
findings when examining the relation between either iron or ferritin with
respect to outcomes.[2-5] It is our impression that heterogeneity in prior
study results may be related to differences in participant sampling
methods, the iron measures used (ferritin, total iron binding capacity,
transferrin saturation, serum iron, and dietary iron intake), and presence
of potential confounding variables that could influence both iron levels
and a given outcome of interest (e.g. inflammation, genetic variants).
Given that iron accumulation patterns have been observed to vary by age
and race as well as sex,[6] we agree that further studies investigating
the role of iron as a potential contributor to cardiovascular risk are
warranted. In particular, interventional studies could evaluate sex-based
differences and also account for variables that could influence both iron
levels and a given outcome of interest (e.g. blood donation and/or
phlebotomy patterns, supplemental intake of iron, dietary patterns
including heme vs. non-heme iron intake, and factors that might elevate
ferritin as part of the acute phase response). We look forward to learning
more about the potential contribution of iron depletion to sex differences
in cardiovascular disease, in particular, as additional evidence emerges
from this understudied field.
References
1. Fredenburgh LE, Merz AA, Cheng S. Haeme oxygenase signalling
pathway: implications for cardiovascular disease. Eur Heart J. 2015 Jun
21;36(24):1512-8. doi: 10.1093/eurheartj/ehv114. Epub 2015 Mar 31. Review.
PubMed PMID: 25827602; PubMed Central PMCID: PMC4475572.
2. Salonen JT, Nyyssonen K, Korpela H, Tuomilehto J, Sepp?nen R,
Salonen R. High stored iron levels are associated with excess risk of
myocardial infarction in eastern Finnish men. Circulation. 1992
Sep;86(3):803-11. PubMed PMID: 1516192.
3. Baer DM, Tekawa IS, Hurley LB. Iron stores are not associated with
acute myocardial infarction. Circulation. 1994 Jun;89(6):2915-8. PubMed
PMID: 8205708.
4. Mu?oz-Bravo C, Guti?rrez-Bedmar M, G?mez-Aracena J, Garc?a-
Rodr?guez A, Navajas JF. Iron: protector or risk factor for cardiovascular
disease? Still controversial. Nutrients. 2013 Jul 1;5(7):2384-404. doi:
10.3390/nu5072384. Review. PubMed PMID: 23857219; PubMed Central PMCID:
PMC3738979.
5. Basuli D, Stevens RG, Torti FM, Torti SV. Epidemiological
associations between iron and cardiovascular disease and diabetes. Front
Pharmacol. 2014 May 20;5:117. doi: 10.3389/fphar.2014.00117. eCollection
2014. Review. PubMed PMID: 24904420; PubMed Central PMCID: PMC4033158.
6. Zacharski LR, Ornstein DL, Woloshin S, Schwartz LM. Association of
age, sex, and race with body iron stores in adults: analysis of NHANES III
data. Am Heart J. 2000 Jul;140(1):98-104. PubMed PMID: 10874269.
The excellently analyzed paper from the Cardiovascular Health Study
on higher circulating adiponectin being associated with elevated risk of
atrial fibrillation (AF) in the elderly [1), calls for focusing attention
on this and analogous paradoxical manifestations accumulating in the
medical literature. The investigation by Macheret and associates involved
886 incident AF events in a cohort of older -predominantly female-...
The excellently analyzed paper from the Cardiovascular Health Study
on higher circulating adiponectin being associated with elevated risk of
atrial fibrillation (AF) in the elderly [1), calls for focusing attention
on this and analogous paradoxical manifestations accumulating in the
medical literature. The investigation by Macheret and associates involved
886 incident AF events in a cohort of older -predominantly female- adults.
It demonstrated a positive and linear, rather than inverse or U-shaped,
association between circulating adiponectin and incident AF, independent
of numerous potential confounders. Females were particularly involved,
although sex-stratified analysis was not provided, African-Americans were
much less susceptible than Whites, as were overweight/obese than lean
people.
Paradoxal behaviour of high adiponectin levels considered as a pro-
inflammatorily converted protein had been published from the Turkish Adult
Risk Factor study since 2008 repeatedly. Independently from obesity and
hyperinsulinemia, serum adiponectin disclosed epidemiologic evidence of
attenuation of anti-inflammatory activities (2). Serum adiponectin proved
to confer no protection against hypertension and was found to diverge in
women from men regarding protection against future coronary disease risk
(3).
Adiponectin is not the only plasma protein to show paradoxical
outcome. HDL-cholesterol and its constituents apolipoprotein(apo) A-I, A-
II, and apoE have formed relevant underlying mechanisms for hypertension,
metabolic syndrome, type-2 diabetes, coronary heart disease, chronic
kidney disease and osteoarthritis. Not cholesterol itself, but cholesterol
-overloaded high-density lipoprotein particles were independently
associated with progression of carotid atherosclerosis in a cardiovascular
disease-free Chinese population. High apo A-I levels, rather than
conferring protection against incident type-2 diabetes, independently
predicted it among Turks. The apoB/LDL-cholesterol ratio, a measure of
small dense low-density lipoprotein particles, was highly predictive of
diabetes in Finnish men.
It may thus be concluded that the enigma of high adiponectin levels
and adverse outcomes in older people is most likely a consequence of
proinflammatory state and autoimmune activation. Diverse factors such as
sex, age, race/ethnicity, susceptibility to impaired glucose tolerance
modulate this phenomenon, formed on one hand by autoimmune components
composed of protective plasma proteins turned proinflammatory, on the
other hand by proteins sustaining epitope damage and partially escaping
immunoassay (4).
References
1. Macheret F, Bartz TM, Djusse L. et al. Higher circulating
adiponectin levels are associated with increased risk of atrial
fibrillation in older adults. Heart 2015;101:1368-1374
2. Onat A, Hergenc G, Dursunoglu D, et al. Relatively high levels of
serum adiponectin in obese women, a potential indicator of anti-
inflammatory dysfunction: Relation to sex hormone-binding globulin. Int J
Biol Sci 2008;4:208-14
3. Onat A, Aydin M, Can G, et al. High adiponectin levels fail to
protect against risk of hypertension and, in women, against coronary
disease: involvement in autoimmunity? World J Diabet 2013;4:219-25
4. Onat A, Can G. Enhanced proinflammatory state and autoimmune
activation: a breakthrough to understanding chronic diseases. Curr Pharm
Design 2014; 20:575-84
Roffi et al.1 report that contemporary outcomes following carotid
stenting (CAS) in large-scale registries were comparable to carotid
endarterectomy (CEA). They also concluded that, over time, complication
rates following CAS had decreased.1
We recently reviewed outcomes after >1,500,000 procedures in 21
administrative dataset registries where procedural death/stroke rates were
reported for both CEA and CAS....
Roffi et al.1 report that contemporary outcomes following carotid
stenting (CAS) in large-scale registries were comparable to carotid
endarterectomy (CEA). They also concluded that, over time, complication
rates following CAS had decreased.1
We recently reviewed outcomes after >1,500,000 procedures in 21
administrative dataset registries where procedural death/stroke rates were
reported for both CEA and CAS.2 One key finding was that CAS was
associated with in-hospital/30-day death/stroke rates which exceeded the
3% American Heart Association (AHA) risk threshold for asymptomatic
patients in 9/21 registries (43%). In symptomatic patients, death/stroke
rates exceeded the 6% AHA risk threshold in 13/18 (72%) registries and
exceeded 10% in 5/18 registries (28%).2 We also found no evidence of a
decline (over time) in procedural risks after CAS.2
There is no doubt that CAS experts are now reporting excellent and
durable outcomes, and it is also true that CAS offers benefits (over CEA)
in terms of avoiding cranial nerve injury. However, there is a discrepancy
between what is being reported in randomised trials and what is happening
in the 'real world', especially in symptomatic patients. Some argue that
most strokes following CAS are non-disabling (i.e. not clinically
important), but Thomas Brott (CREST Principal Investigator) has stated
that any perioperative stroke is associated with poorer long term
survival, just as with perioperative myocardial infarction.3
In conclusion, we agree with Marco Roffi that with better patient
selection, improvements in stent design/protection devices and (most
importantly) centralization of CAS procedures into high-volume centres,
procedural risks following CAS will become similar to CEA. But, is the
movement into 'higher volume' centres really happening? Sadly, evidence
suggests that in the USA, if nowhere else, many CAS practitioners perform
only 1-3 procedures each year,4 making it impossible to ever overcome the
learning curve.
The future is certainly looking brighter for CAS, but key opinion
leaders now need to 'step up to the plate' to ensure that patients are
only treated by experienced CAS practitioners with audited outcomes within
AHA risk thresholds. This will not be popular, but evidence suggests that
until it does, nothing will change.
References
1. Roffi M, Kulcsar Z, Carrera E, et al. Carotid artery stenting.
Heart 2016 Mar 4. pii: heartjnl-2015-307638. doi: 10.1136/heartjnl-2015-
307638 [Epub ahead of print]
2. Paraskevas KI, Kalmykov EL, Naylor AR. Stroke/Death Rates
Following Carotid Artery Stenting and Carotid Endarterectomy in
Contemporary Administrative Dataset Registries: A Systematic Review. Eur J
Vasc Endovasc Surg. 2016;51:3-12.
3. von Allmen R. Dismantling the different myths around the CREST
trial. Vascular News. 2012;53(1):10. Available at:
http://www.vascularnews.com/vn-newspaper-
pdfs?DocumentScreen=detail&cl=371&ccs=655. Accessed on March 23, 2016.
4. Choi JC, Johnston SC, Kim AS. Early outcomes after carotid artery
stenting compared with endarterectomy for asymptomatic carotid stenosis.
Stroke. 2015;46:120-125.
We read with interest the letter by dr Shah [1] regarding our recent
meta-analysis: "Complete revascularisation in ST-elevation myocardial
infarction and multivessel disease: meta-analysis of randomised controlled
trials" [2]. The meta-analysis was designed to compare complete
multivessel PCI (MV-PCI) with non-complete MV-PCI in ST-elvation
myocardial infarction (STEMI) and MV disease. Complete MV...
We read with interest the letter by dr Shah [1] regarding our recent
meta-analysis: "Complete revascularisation in ST-elevation myocardial
infarction and multivessel disease: meta-analysis of randomised controlled
trials" [2]. The meta-analysis was designed to compare complete
multivessel PCI (MV-PCI) with non-complete MV-PCI in ST-elvation
myocardial infarction (STEMI) and MV disease. Complete MV-PCI was defined
as revascularisation to non-infarct-related artery lesions during index
procedure, non-complete MV-PCI-encompassed culprit-only revascularization
(COR) and staged approaches. First of all, we appreciate the comments by
Shah and are glad that our research has become of interest to a large
international readership. At the same time we believe that criticism about
methodology or clinical meaningfulness of a meta- analysis should be based
upon specific clinical knowledge of the topic, and, above all, careful
reading of the meta-analysis design.
Shah suggests that because the majority of staged procedures were
performed within days to weeks of their index procedures, they would be
considered more like complete than incomplete revascularizations over a 12
-month follow-up. This is a simply arbitrary reclassification, given the
large time discrepancy between the two approaches in all included studies
that were however not designed to define an optimal timing, nor it was the
primary focus of our paper. As a result, Shah speculates that staged PCI
should became anyhow bundled in the same group with complete
revascularization. This arbitrary re-reclassification is also in contrast
with the natural history of the untreated coronary lesions. These patients
present a different risk profile from those allocated to staged PCI; as a
reflection of this, the untreated lesions over time in the second group
have led to an accrual over time of the MI rates in the IRA- only treated
patients; a difference in time in this group is pivotal to demonstrate the
impact of leaving a non culprit plaque untreated; same applies to staged
procedures. The approach in our analysis therefore reflects true clinical
practice and indeed is based on coronary- and risk profile evaluation of
the patients with non culprit plaques. An arbitrary, fixed time-frame
second revascularisation for all patients with non culprit lesions is not
only infeasible in clinical setting but, indeed, dangerous treating in the
same way patients with different coronary artery lesions; as a sensitivity
analysis, a stratified meta-analysis by intervention in the control group
was performed as well. Our study was not designed to compare in the same
setting complete revascularization (CR) vs index hospitalization CR vs
later date CR vs IRA only revascularization; neither was any study
conducted to date.
Secondly, Shah is concerned about the validity of the findings due to
inconsistency driven by inclusion of the entire complete revascularization
cohort from the Complete versus Culprit-Lesion Only Primary PCI Trial
(CvLPRIT), while in the Supplementary Table 5 CR was performed during the
index procedure for 97 patients [3]. Current meta-analysis was performed
according to intention-to-treat (ITT) which is recommended as the least
biased way to estimate intervention effects in randomized trials [4]:
principles of ITT analyses are, first of all, to classify participants in
the intervention groups to which they were randomized, regardless of the
intervention they actually received, therefore inclusion of post-hoc
analyses which is the case for Supplementary Table 5, is not only
forbidden by design of the meta-analysis but may also lead to attrition
bias with patients dropping out from the initial randomization group and
consequently to results that are unequal in regard to exposure and/or
outcome. In the methods section of the CvLPRIT one reads that "if
randomized to complete revascularization, it was mandated that the IRA be
treated first. If there were no clinical contraindications, complete
revascularization was recommended at the same sitting to reduce multiple
vascular punctures, avoid prolonged hospitalization, and attenuate
potential patient dropout". Decision for the procedure to be staged was
based on clinical reasons and left to the operator, which we cannot answer
for.
Thirdly, Shah cited part of the methods from the study by Maamoun et
al. [5] and concluded this study was an observational cohort; this remark
is however incorrect because what is reported also in the abstract is: "A
total of 78 patients (72 males and 6 females) with ST-elevation MI
presented within 12 h from the onset of symptom who had at least two
angiographically-documented diseased coronary arteries (luminal diameter
narrowing ?70%) and received primary PCI were included. They were randomly
assigned to receive either PCI for culprit vessel only in the initial
procedure (SR group) followed by another session of angioplasty to other
diseased vessels (within 7 days), or (CR group) consisted of 42 patients
who had received complete revascularization during the initial procedure
after intracoronary administration of nitroglycerin to avoid stenting of
functionally nonsignificant lesions". We have no reasons to believe it was
otherwise.
Finally, Shah advises that the trial by Ghani et al. [6] should have
had as well been included in the meta-analysis. While report by Ghani et
al. comprises a follow-up study, the main results derive from the article
by Dambrink et al. [7]. This study was intentionally excluded as not
pertinent to the design of the meta-analysis. Dambrink et al. randomized
STEMI patients to invasive and conservative treatment after primary
angioplasty. In the invasive- group, "ischaemia-guided additional
revascularisation was performed during the in-hospital phase after primary
PCI or in an out-patient setting but no later than three weeks after
STEMI", therefore nowhere close to complete MV-PCI during index procedure.
The last claim of other studies intentionally omitted, undermining the
validity of this meta-analysis, we leave to the discretion of the Heart
Editor and the Readership.
References
1. Rahman Shah. Letter to the Editor regarding heartjnl-2014-
307293.R2 - Complete Revascularization in ST-Elevation Myocardial
Infarction and Multivessel Disease. Meta-Analysis of Randomized Controlled
Trials. 17.03.2016
2. Kowalewski M, Schulze V, Berti S, Waksman R, Kubica J,
Kolodziejczak M, Buffon A, Suryapranata H, Gurbel PA, Kelm M, Pawliszak W,
Anisimowicz L, Navarese EP. Complete revascularisation in ST-elevation
myocardial infarction and multivessel disease: meta-analysis of randomised
controlled trials. Heart 2015;101:1309-1317.
3. Gershlick AH, Khan JN, Kelly DJ, et al. Randomized trial of
complete versus lesion-only revascularization in patients undergoing
primary percutaneous coronary intervention for STEMI and multivessel
disease: the CvLPRIT trial. J Am Coll Cardiol. 2015;65:963-72.
4. Newell DJ. Intention-to-treat analysis: implications for
quantitative and qualitative research. Int J Epidemiol 1992;21:837-841.
5. Maamoun W, Elkhaeat N, Elarasy R. Safety and feasibility of
complete simultaneous revascularization during primary PCI in patients
with STEMI and multivessel disease. Egyptian Heart J 2011;63:39-43.
6. Ghani A1, Dambrink JH, van 't Hof AW, et al. Treatment of non-
culprit lesions detected during primary PCI: long-term follow-up of a
randomised clinical trial. Neth Heart J. 2012 Sep; 20(9): 347-353
7. Dambrink JH, Debrauwere JP, van 't Hof AW, Ottervanger JP,
Gosselink AT, Hoorntje JC, de Boer MJ, Suryapranata H. Non-culprit lesions
detected during primary PCI: treat invasively or follow the guidelines?
EuroIntervention 2010;5:968-975.
ALICE was beginning to get very tired of sitting by her sister on the bank and of having nothing to do: once or twice she had peeped into the book her sister was reading, but it had no pictures or conversations in it, "and what is the use of a book," thought Alice, "without pictures or conversations?'
So she was considering, in her own mind (as well as she could, for the hot day made her feel very sleepy and stupid), whether the pleasure of making a daisy-chain would be worth the trouble of getting up and picking the daisies, when suddenly a White Rabbit with pink eyes ran close by her.
There was nothing so very remarkable in that; nor did Alice think it so very much out of the way to hear the Rabbit say to itself "Oh dear! Oh dear! I shall be too late!" (when she thought it over afterwards it occurred to her that she ought to have wondered at this, but at the time it all seemed quite natural); but, when the Rabbit actually took a watch out of its waistcoat-pocket, and looked at it, and then hurried on, Alice started to her feet, for it flashed across her mind that she had never before seen a rabbit with either a waistcoat-pocket, or a watch to take out of it, and burning with curiosity, she ran across the field after it, and was just in time to see it pop down a large rabbit-hole under the hedge.
To the Editor:
We read with great interest the recent meta-analysis by Kowalewski et al.[1] The authors should be congratulated for their work. However, we would like to make few comments about some issues with the meta-analysis.
First, complete revascularizations (CRs) done as staged procedures (SPs) were analyzed with the incomplete revascularization group, but endpoints were measured at a median follow-up of 12 months. Becaus...
To the Editor:
We read with great interest the recent meta-analysis by Kowalewski et al.[1] The authors should be congratulated for their work. However, we would like to make few comments about some issues with the meta-analysis.
First, complete revascularizations (CRs) done as staged procedures (SPs) were analyzed with the incomplete revascularization group, but endpoints were measured at a median follow-up of 12 months. Because the majority of SPs were performed within days to weeks of their index procedures, clinical wisdom suggests they would behave more like CRs than incomplete revascularizations over a 12-month follow-up. Therefore, we believe that from statistical and clinical points of view, CRs performed as SPs should have been included in the complete revascularization group, as was done in other meta-analyses and randomized trials.[2] Furthermore, the authors did not consistently analyzed CRs performed as SPs with the incomplete arm. In the Complete versus Culprit-Lesion Only Primary PCI Trial (CvLPRIT), CR was performed during the index procedure for 97 patients (Supplementary Table 5 in the CvLPRIT trial),[2] but this group (for this meta-analysis)was combined with patients receiving CRs as SPs, bringing the total to 150. This inconsistency significantly impacts the validity of the meta-analysis.
In addition, the title indicates the study was a meta-analysis of randomized trials, yet it included the study by Maamoun et al, an observational cohort study,[3] as evidenced by a statement in the Methods section. Maamoun et al state, "Group 1 consisted of 36 patients presented in the 1st year of the study and had undergone primary PCI for culprit vessel only in the initial procedure followed by another session of angioplasty to other diseased vessels and group 2 consisted of 42 patients presented in the 2nd year of the study and had received complete revascularization during the initial procedure."
Finally, the authors did not include a trial by Ghani et al.[4] No reason for this omission was mentioned in the Methods or Discussion. Therefore, we wonder if other studies were also omitted, undermining the validity of this meta-analysis.
References:
1. Kowalewski M, Schulze V, Berti S, et al. Complete revascularisation in ST-elevation myocardial infarction and multivessel disease: meta-analysis of randomised controlled trials. Heart. 2015;101(16):1309-17.
2. Gershlick AH, Khan JN, Kelly DJ, et al. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial. J Am Coll Cardiol. 2015;65:963-72.
3. Maamoun W, Elkhaeat N, Elarasy R. Safety and feasibility of complete simultaneous revascularization during primary PCI in patients with STEMI and multivessel disease. Egyptian Heart J 2011;63:39-43.
4. Ghani A1, Dambrink JH, van 't Hof AW, et al. Treatment of non-culprit lesions detected during primary PCI: long-term follow-up of a randomised clinical trial. Neth Heart J. 2012 Sep; 20(9): 347-353.
Atrial fibrillation (AF) constitutes a major risk factor for stroke and death.1 ,2 The potential of biomarkers to improve the prognostication concerning stroke and other cardiovascular events in patients with AF is gaining strength of evidence and clinical promise. In particular the biomarkers of cardiovascular stress and dysfunction such as cardiac troponin (cTn), a marker of myocardial cell damage; N-terminal B-type natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction; and growth-differentiation factor-15 (GDF-15), a marker of inflammation and oxidative stress, have been shown to be strong independent predictors.3–8 Although inflammatory activation has been linked to the occurrence of AF and to a prothrombotic state, the association with subsequent cardiovascular events during treatment with oral anticoagulation has not been fully established.9–14 Prior studies evaluating the relation between inflammation and cardiovascular events in patients with AF have often been exploratory and did not take into account the protective effect of oral anticoagulation. In addition the associations with outcomes have not been fully adjusted for other risk indicators, in particular other cardiovascular biomarkers, which recently have show
The interesting paper of Merz and Cheng did not mention iron as a plausible non-hormonal factor, which might in part explain the sex differences in cardiovascular aging [1].
Mounting evidence suggests that the metabolic derangements and detrimental cardiovascular effects usually attributed to menopause represent only a mere consequence of the older age of menopausal women, rather than related to the loss of ov...
We thank Dr. Goldstein for bringing to our attention the iron hypothesis as a potential non-hormonal factor contributing to sex differences in cardiovascular aging. We also find intriguing the possibility that iron depletion in menstruating women may be cardio- protective. We had previously been aware of the potential role of iron as a byproduct of heme-oxygenase activity in mediating cardiometabolic risk,[1] with a numb...
Testing article responses 2
Testing article responses
The excellently analyzed paper from the Cardiovascular Health Study on higher circulating adiponectin being associated with elevated risk of atrial fibrillation (AF) in the elderly [1), calls for focusing attention on this and analogous paradoxical manifestations accumulating in the medical literature. The investigation by Macheret and associates involved 886 incident AF events in a cohort of older -predominantly female-...
Roffi et al.1 report that contemporary outcomes following carotid stenting (CAS) in large-scale registries were comparable to carotid endarterectomy (CEA). They also concluded that, over time, complication rates following CAS had decreased.1
We recently reviewed outcomes after >1,500,000 procedures in 21 administrative dataset registries where procedural death/stroke rates were reported for both CEA and CAS....
To the Editor:
We read with interest the letter by dr Shah [1] regarding our recent meta-analysis: "Complete revascularisation in ST-elevation myocardial infarction and multivessel disease: meta-analysis of randomised controlled trials" [2]. The meta-analysis was designed to compare complete multivessel PCI (MV-PCI) with non-complete MV-PCI in ST-elvation myocardial infarction (STEMI) and MV disease. Complete MV...
ALICE was beginning to get very tired of sitting by her sister on the bank and of having nothing to do: once or twice she had peeped into the book her sister was reading, but it had no pictures or conversations in it, "and what is the use of a book," thought Alice, "without pictures or conversations?'
So she was considering, in her own mind (as well as she could, for the hot day made her feel very sleepy and stupid), whether the pleasure of making a daisy-chain would be worth the trouble of getting up and picking the daisies, when suddenly a White Rabbit with pink eyes ran close by her.
There was nothing so very remarkable in that; nor did Alice think it so very much out of the way to hear the Rabbit say to itself "Oh dear! Oh dear! I shall be too late!" (when she thought it over afterwards it occurred to her that she ought to have wondered at this, but at the time it all seemed quite natural); but, when the Rabbit actually took a watch out of its waistcoat-pocket, and looked at it, and then hurried on, Alice started to her feet, for it flashed across her mind that she had never before seen a rabbit with either a waistcoat-pocket, or a watch to take out of it, and burning with curiosity, she ran across the field after it, and was just in time to see it pop down a large rabbit-hole under the hedge.
Atrial fibrillation (AF) constitutes a major risk factor for stroke and death.1 ,2 The potential of biomarkers to improve the prognostication concerning stroke and other cardiovascular events in patients with AF is gaining strength of evidence and clinical promise. In particular the biomarkers of cardiovascular stress and dysfunction such as cardiac troponin (cTn), a marker of myocardial cell damage; N-terminal B-type natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction; and growth-differentiation factor-15 (GDF-15), a marker of inflammation and oxidative stress, have been shown to be strong independent predictors.3–8 Although inflammatory activation has been linked to the occurrence of AF and to a prothrombotic state, the association with subsequent cardiovascular events during treatment with oral anticoagulation has not been fully established.9–14 Prior studies evaluating the relation between inflammation and cardiovascular events in patients with AF have often been exploratory and did not take into account the protective effect of oral anticoagulation. In addition the associations with outcomes have not been fully adjusted for other risk indicators, in particular other cardiovascular biomarkers, which recently have show
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