Notwithstanding the high costs and lack of reimbursement associated with the use of positron emission tomography/computed tomography(PET/CT) in suspected cardiac implantable electronic device (CIED) infection(1), the ability of this modality to distinguish between infective and non infective vegetations is a powerful argument for its inclusion in the workup of suspected CIED. Evidence of the ability to make this distinction comes from two sources(2)(3). Firstly, in a retrospective study of 177 transoesophageal echocardiographic studies performed on 153 consecutive patients, a visible mass was observed on a device lead in 25 instances. In 11 studies this was a lead vegetation, in 13 instances only lead strands were seen, and in one instance a lead vegetation coexisted with a lead strand. Nevertheless, 18 of the 25 patients with lead-associated masses had no other evidence of infection. In that study the presence or absence of infection was adjudicated by three clinical investigators who independently reviewed all available clinical data without knowledge of the echocardiographic results(2). In another study, 63 consecutive patients(mean age 68.6) with suspected CIED were evaluated both by echocardiography(tranasthoracic and transoesophageal) and by PET/CT. Echocardiography was associated with a positive predictive value(PPV) of 83.3%, and a negative predictive value(NPV) of 69.2%. For PET/CT, PPV and NPV amounted to 100% and 93.9%, respectively(3). The additional ut...
Notwithstanding the high costs and lack of reimbursement associated with the use of positron emission tomography/computed tomography(PET/CT) in suspected cardiac implantable electronic device (CIED) infection(1), the ability of this modality to distinguish between infective and non infective vegetations is a powerful argument for its inclusion in the workup of suspected CIED. Evidence of the ability to make this distinction comes from two sources(2)(3). Firstly, in a retrospective study of 177 transoesophageal echocardiographic studies performed on 153 consecutive patients, a visible mass was observed on a device lead in 25 instances. In 11 studies this was a lead vegetation, in 13 instances only lead strands were seen, and in one instance a lead vegetation coexisted with a lead strand. Nevertheless, 18 of the 25 patients with lead-associated masses had no other evidence of infection. In that study the presence or absence of infection was adjudicated by three clinical investigators who independently reviewed all available clinical data without knowledge of the echocardiographic results(2). In another study, 63 consecutive patients(mean age 68.6) with suspected CIED were evaluated both by echocardiography(tranasthoracic and transoesophageal) and by PET/CT. Echocardiography was associated with a positive predictive value(PPV) of 83.3%, and a negative predictive value(NPV) of 69.2%. For PET/CT, PPV and NPV amounted to 100% and 93.9%, respectively(3). The additional utility of PET/CT is the ability to detect "unsuspected extracardiac sites of infection in up to 23% of patients with device-related sepsis"(4), thereby facilitating the fulfilment of Duke criteria for infective endocarditis(5). In those instances where the sensitivity of PET/CT is suboptimal that shortcoming is largely attributable to prior antibiotic use(6). Furthermore, negative PET/CT also identifies a group of patients who have excellent outcome without device extraction(6).
I have no funding, and no conflict of interest.
References
(1) DeSimone DC., Sohali MR., Mulpuru SK
Contemporary management of cardiac implantable electronic device infection
Heart 2019;105:961-965
(2)Downey BC., Juselius WE.,Pandian NG., Estes NAM., Link MS
Incidence and significance of pacemaker and implantable cardioverter-defibrillator lead masses discovered during transesophageal echocardiography
PACE 2011;34:679-683
(3) Erba PA., Sollini M., Conti U., Bandera F., Tascini C., De Tommasi SM
Radiolabeled WBC scintigraphy in the diagnostic work up of patients with suspected device-related infections
JACC Cardiovascular Imaging 2013;6:1075-1086
(4) Gutierrez-Carretero E., Rezaei K., Rodriguez-Mora F., de Alarcon A
Infections on cardiovascular implantable electronic devices: A critical review
Medical Research Archives 2019;Issue 3;page 1 to 64
(5) Tak T., Shukla S
Molecular diagnosis of infective endocarditis: a helpful addition to Duke criteria
Clin Med Res 2004;2:206-208
(6) Sarrazin J-F., Phillippon F., Trottier M., Tessier M
Role of radionuclide imaging for diagnosis of device and prosthetic valve infections
World Journal of Cardiology 2016;8:534-546
Under the heading "Changes in kidney function during intercurrent illness"(1) mention must be made of the risk of acute kidney injury when nonsteroidal anti inflammatory drugs(NSAIDs) are prescribed for acute gout, the latter complication(the equivalent of "intercurrent illness") sometimes documented as a consequence of diuretic use in congestive heart failure(CHF)(2). Coprescription of NSAIDs, diuretics, and angiotensin converting enzyme inhibitors(or angiotensin receptor blockers), so-called triple therapy, is associated with increased risk of acute kidney injury(rate ratio 1.31, 95% Confidence Interval 1.12 to 1.53)(3). This was shown in a nested case-control study which enrolled patients in whom hypertension was the indication for prescription of diuretics and/or angiotensin converting enzyme inhibitors(or angiotensin receptor blockers)(3), but might be equally applicable in the context of CHF. Additionally, among CHF patients who have a drug regime which includes spironolactone, the use of NSAIDs might increase the risk of hyperkalaemia. The rationale is that NSAIDs "interfere with the stimulatory effect of prostaglandins on the release of renin"(4). The risk of hyperkalaemia may be compounded by concurrent use of beta adrenergic blocking agents(4).
For all the above reasons, NSAIDs should be contraindicated in CHF patients with gout. The recommended alternatives include colcichine(5) and intraarticuoar corticosteroids(6), resp...
Under the heading "Changes in kidney function during intercurrent illness"(1) mention must be made of the risk of acute kidney injury when nonsteroidal anti inflammatory drugs(NSAIDs) are prescribed for acute gout, the latter complication(the equivalent of "intercurrent illness") sometimes documented as a consequence of diuretic use in congestive heart failure(CHF)(2). Coprescription of NSAIDs, diuretics, and angiotensin converting enzyme inhibitors(or angiotensin receptor blockers), so-called triple therapy, is associated with increased risk of acute kidney injury(rate ratio 1.31, 95% Confidence Interval 1.12 to 1.53)(3). This was shown in a nested case-control study which enrolled patients in whom hypertension was the indication for prescription of diuretics and/or angiotensin converting enzyme inhibitors(or angiotensin receptor blockers)(3), but might be equally applicable in the context of CHF. Additionally, among CHF patients who have a drug regime which includes spironolactone, the use of NSAIDs might increase the risk of hyperkalaemia. The rationale is that NSAIDs "interfere with the stimulatory effect of prostaglandins on the release of renin"(4). The risk of hyperkalaemia may be compounded by concurrent use of beta adrenergic blocking agents(4).
For all the above reasons, NSAIDs should be contraindicated in CHF patients with gout. The recommended alternatives include colcichine(5) and intraarticuoar corticosteroids(6), respectively. According to the American College of Physicians Clinical Practice Guideline moderate quality evidence shows that colcichine 1.2 mg followed by 0.6 mg after 1 hour can be as effective, for pain control, as 1.2 mg followed by 0.6 mg/h for 6 hours. The lower dose regime is associated with lower prevalence of diahrroea(23% vs 77%)(5). The alternative is the use of intra articular corticosteroids, advocated in Australia(6), but not licensed for use in the UK.
I have on funding and no conflict of interest
References
(1) Change in renal function associate with drug treatment in heart failure: national guidance
Heart June 2019
(2) Spieker LE., Ruschitzka FT., Luscher TF., Noll G
The management of hyperuricemia and gout in patients with heart failure
Eur J Heart Failure 2002;4:403-410
(3)Lapi F., Azoulay L., Yin H., Nessim SJ., Suissa S
Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with nonsteroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study
BMJ 2013;346:e8525
(4) Palmer BF
Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system
N Engl J Med 2004;351:585-592
(5) Qaseem A., Harris RP., Forciea MA., for the Clinical Guideline Committee of the American College of Physicians
Management of acute and recurrent gout: A clinical practice guideline for the American College of Physicians
Ann Intern Med 2017;166:58-68
(6) Robinson PC., Stamp LK
The management of gout: Much has changed
RACGP 2016;45:299-302
We are grateful for the comments by David P Foley, Zoe Harcombe and Uffe Ravnsker on our paper.
Both American and UK guidelines for the treatment of cholesterol,[1,2] recommend monitoring percent reduction in low-density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. Our recently published paper [3] examined LDL-C reduction among patients initiating statins in the real-world setting.
With regard to the points raised:
Why didn’t you analyse the possible reasons for the observed ‘findings’?
Our study was not designed to establish causality so we are unable to analyse possible reasons for the observed findings. We are, however, undertaking further research to establish these latter.
David P Foley notes in his response, ‘it is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect’. However, it is important to avoid any erroneous impression that patients are started on low dose statins in primary care. As shown in Table 1, most patients in this study were actually prescribed moderate and high potency statins (70.9% in the sub-optimal responders compared to 81.8% in the optimal responders).
A study by Vupputuri et al,[4] examined LDL-C reduction and adherence among high-risk patients initiating statins in a real-world setting using electronic health records of 1,066 patients in the US. Of patients with high adherence...
We are grateful for the comments by David P Foley, Zoe Harcombe and Uffe Ravnsker on our paper.
Both American and UK guidelines for the treatment of cholesterol,[1,2] recommend monitoring percent reduction in low-density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. Our recently published paper [3] examined LDL-C reduction among patients initiating statins in the real-world setting.
With regard to the points raised:
Why didn’t you analyse the possible reasons for the observed ‘findings’?
Our study was not designed to establish causality so we are unable to analyse possible reasons for the observed findings. We are, however, undertaking further research to establish these latter.
David P Foley notes in his response, ‘it is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect’. However, it is important to avoid any erroneous impression that patients are started on low dose statins in primary care. As shown in Table 1, most patients in this study were actually prescribed moderate and high potency statins (70.9% in the sub-optimal responders compared to 81.8% in the optimal responders).
A study by Vupputuri et al,[4] examined LDL-C reduction and adherence among high-risk patients initiating statins in a real-world setting using electronic health records of 1,066 patients in the US. Of patients with high adherence in the study, 42.3% still did not achieve the LDL-C target, compared to 54.7% and 79.7% of those with intermediate and low-statin adherence.
Statin potency and adherence might explain some of the variations observed in LDL-C response. We, however, believe there might be other mediating variables or influences and we seek to find these in our on-going research.
This paper needs to be corrected to adjust for lifestyle differences.
Standard and recognised practice in peer-reviewed quantitative research studies is to report a baseline description of the study population including the proportion of missing variables.
The selection of potential covariates to adjust in our statistical model was therefore not determined simply by the observed patient characteristics that were found to be different between the two patient groups as suggested by Zoe Harcombe. The inclusion of all clinical and other related variables in a model, regardless of significance, in order to control for confounding can lead to unreliable estimates of effects and large standard errors.
An acceptable and appropriate approach for selection of potential covariates was used in our paper. A list of 31 potential variables (list provided in supplementary file of the paper) including alcohol misuse, smoking, gender were systematically and objectively assessed. The potential covariates that met the criteria outlined in the methods section, according to change in estimation criterion of effect estimator by 5% or more,[5] were selected for adjustment in the final regression models. Most of the 31 variables explored did not meet this criterion.
Questionable benefit of increasing the degree of cholesterol lowering
Our paper highlights the benefit of statins in reducing future cardiovascular disease (CVD) risk for both optimal and sub-optimal responders. For every 1 mmol/l fall in LDL-C, there was a 6% lower risk of CVD in those with < 40% reduction in LDL-C, compared to a 13% drop in those who attained the recommended 40% or more reduction. In a Cochrane Review by Taylor et al, reductions in all‐cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins.[6]
In relation to stress-related disorders as strong predictors of CVD, we note stress-related disorders show substantial comorbidity with other psychiatric disorders [7]. In our paper, severe mental illness was one of the potential covariates (Supplementary file – Appendix 1) assessed but was not found to be significantly associated with the exposure and outcome in our study.
To conclude, we would emphasise the main message from our paper. In the real-world primary care setting, optimal lowering of LDL-C is not observed within 2 years in over half of patients and these patients will experience significantly increased risk of future CVD. There is therefore a need for monitoring of LDL-C response and consideration of ongoing titration and appropriate management to achieve the recommended reduction in LDL-C.
References:
1. National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. London: : National Institute for Health and Care Excellence 2016.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129:S1-45. doi:10.1161/01.cir.0000437738.63853.7a
3.Akyea RK, Kai J, Qureshi N, et al. Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease. Heart 2019;:heartjnl-2018-314253. doi:10.1136/heartjnl-2018-314253
4. Vupputuri S, Joski PJ, Kilpatrick R, et al. LDL cholesterol response and statin adherence among high-risk patients initiating treatment. Am J Manag Care 2016;22:e106-15.
5. Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol 1993;138:923–36.
6. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease (Review). Cochrane Database Syst Rev Published Online First: 2013. doi:10.1002/14651858.CD004816.pub5.www.cochranelibrary.com
7. Song H, Fang F, Arnberg FK, et al. Stress related disorders and risk of cardiovascular disease: population based, sibling controlled cohort study. BMJ 2019;365:l1255. doi:10.1136/bmj.l1255
This study has already been inappropriately quoted in the media which is what the public read and misinformation is propagating. The authors need to take some responsibility for failing to point out that the dosing of the statins prescribed (most likely archaic low dose simvastatin) isn't analysed and long term compliance isn't addressed in this ' primary prevention population based longitudinal non interventional study'
Cardiologists are going to inundated with questions from patients with coronary disease on statins who have misinterpreted information which is incomplete and misrepresented - the title of the study needs to be highlighted 'Initiation of statins' is well put and needs to be remembered. The study cannot address the 'ongoing management' of cardiovascular risk with appropriate cardiovascular investigation of patients and optimization of preventative strategies as this study does not address this crucial aspect.
It is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect so that low doses initiated in general practice are actually ineffective and this is what the study shows NOT that statins are ineffective but that medical practice of blanket prescribing of low doses of statins is ineffective without monitoring of response and ongoing titration to achieve evidence based targets. This omission from the conclusions needs to be corrected and it ne...
This study has already been inappropriately quoted in the media which is what the public read and misinformation is propagating. The authors need to take some responsibility for failing to point out that the dosing of the statins prescribed (most likely archaic low dose simvastatin) isn't analysed and long term compliance isn't addressed in this ' primary prevention population based longitudinal non interventional study'
Cardiologists are going to inundated with questions from patients with coronary disease on statins who have misinterpreted information which is incomplete and misrepresented - the title of the study needs to be highlighted 'Initiation of statins' is well put and needs to be remembered. The study cannot address the 'ongoing management' of cardiovascular risk with appropriate cardiovascular investigation of patients and optimization of preventative strategies as this study does not address this crucial aspect.
It is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect so that low doses initiated in general practice are actually ineffective and this is what the study shows NOT that statins are ineffective but that medical practice of blanket prescribing of low doses of statins is ineffective without monitoring of response and ongoing titration to achieve evidence based targets. This omission from the conclusions needs to be corrected and it needs to be emphasized that patients with cardiovascular disease on proper high dose statins are not part of this study at all.
The conclusion of this article was twofold: 1) approximately half of primary care patients put on statins did not achieve at least a 40% reduction in LDL-Cholesterol (the sub-optimal group) and 2) those who did (the optimal group) had fewer cardiovascular incidents over the next (approximately six) years.
Table 1 in the paper shows that the sub-optimal group have 1.43 times the “alcohol misuse” of the optimal group. There is no more information on alcohol consumption beyond this. Were the alcohol misusers also far less likely to be non or moderate drinkers and far more likely to be heavy and frequent drinkers?
The smoking information shows that, from the limited information available, the sub-optimal group were 25% more likely to be smokers. However, there is no smoking information for 96% of patients. There is no activity information – were the drinking/smokers more likely to be sedentary? Were they more likely to be obese?
There were more men in the sub-optimal group. The sub-optimal patients were more likely to be poorly-controlled diabetics and less likely to have hypertension treated.
Correspondence with the researchers confirmed that the HRs in Table 2 were not adjusted for anything other than age and baseline LDL-Cholesterol. They were not adjusted for alcohol misuse, or smoking, or gender, or any other lifestyle factors that were known to be different between the two groups – even with vast amounts of missing information.
The conclusion of this article was twofold: 1) approximately half of primary care patients put on statins did not achieve at least a 40% reduction in LDL-Cholesterol (the sub-optimal group) and 2) those who did (the optimal group) had fewer cardiovascular incidents over the next (approximately six) years.
Table 1 in the paper shows that the sub-optimal group have 1.43 times the “alcohol misuse” of the optimal group. There is no more information on alcohol consumption beyond this. Were the alcohol misusers also far less likely to be non or moderate drinkers and far more likely to be heavy and frequent drinkers?
The smoking information shows that, from the limited information available, the sub-optimal group were 25% more likely to be smokers. However, there is no smoking information for 96% of patients. There is no activity information – were the drinking/smokers more likely to be sedentary? Were they more likely to be obese?
There were more men in the sub-optimal group. The sub-optimal patients were more likely to be poorly-controlled diabetics and less likely to have hypertension treated.
Correspondence with the researchers confirmed that the HRs in Table 2 were not adjusted for anything other than age and baseline LDL-Cholesterol. They were not adjusted for alcohol misuse, or smoking, or gender, or any other lifestyle factors that were known to be different between the two groups – even with vast amounts of missing information.
The entire differences between the groups for CVD events were credited to statins/the degree of cholesterol-lowering. None to lifestyle differences. This should be corrected, as it is wrong and misleading.
In their prospective cohort study of 165,411 primary care patients, Akyea et al. claim that suboptimal responders on statin treatment will experience significantly increased risk of future cardiovascular disease (CVD)(1). As many cardiovascular events may heal without serious health problems, we consider mortality as the most important outcome. Among the 80,802 patients with optimal cholesterol lowering, 821 (1.01 %) died from CVD. Among the 84,609 patients with suboptimal cholesterol-lowering 873 (1.03 %) died. This means that to prevent one cardiovascular death by optimal cholesterol lowering you have to increase the degree of lowering in 5,000 patients for six years. This is hardly a benefit because several independent researchers have reported that serious side effects from statin treatment are much more common than reported in the statin trials (2). The small numbers reported in the trial reports are achieved by excluding participants who suffer from side effects of the drug during a few weeks long run-in period before the start of the trial. That this is an effective method to lower the number of side effects appeared in the IDEAL trial where this method wasn´t used and where a high statin dose was compared with a low dose, because in that trial almost half of the participants in both groups suffered from serious side effects (2).
Furthermore, Akyea et al. have not reported total mortality in the two groups. This failure may introduce another bias because tota...
In their prospective cohort study of 165,411 primary care patients, Akyea et al. claim that suboptimal responders on statin treatment will experience significantly increased risk of future cardiovascular disease (CVD)(1). As many cardiovascular events may heal without serious health problems, we consider mortality as the most important outcome. Among the 80,802 patients with optimal cholesterol lowering, 821 (1.01 %) died from CVD. Among the 84,609 patients with suboptimal cholesterol-lowering 873 (1.03 %) died. This means that to prevent one cardiovascular death by optimal cholesterol lowering you have to increase the degree of lowering in 5,000 patients for six years. This is hardly a benefit because several independent researchers have reported that serious side effects from statin treatment are much more common than reported in the statin trials (2). The small numbers reported in the trial reports are achieved by excluding participants who suffer from side effects of the drug during a few weeks long run-in period before the start of the trial. That this is an effective method to lower the number of side effects appeared in the IDEAL trial where this method wasn´t used and where a high statin dose was compared with a low dose, because in that trial almost half of the participants in both groups suffered from serious side effects (2).
Furthermore, Akyea et al. have not reported total mortality in the two groups. This failure may introduce another bias because total mortality was higher in at least seven
statin trials (AFCAPS/TEXcaps, ASPEN, TNT, SPARCL, DEBATE, SEAS and GISSI-HF) (2).
A relevant question is also whether the higher risk among those with suboptimal cholesterol lowering was due to their higher cholesterol or whether they have been more stressed than the optimally treated patients because in a recent study by Song et al (3) stress related disorders were strong predictors of CVD. This fact induces yet another bias in the study by Akyea et al. because several studies have shown that stress may raise serum cholesterol substantially (4-7), and stress may increase the risk of CVD in many other ways (8). We consider that mental stress is the most likely explanation of the difference because a recent review of the medical literature has documented that the general view about the role of cholesterol in CVD does not satisfy any of Bradford Hill´s criteria for a medical hypothesis (2).
1. Akyea RK, Kai J, Qureshi N, et al. Heart 2019;0:1–7. doi:10.1136/heartjnl-2018-314253
2. Ravnskov U, de Lorgeril M, Diamond DM, et al. LDL-C does not cause cardiovascular disease: a comprehensive review of current literature. Exp Rev Clin Pharmacol 2018;11:959-70. doi: 10.1080/17512433.2018.1519391.
3. Song H, Fang F, Arnberg FK et al. Stress related disorders and risk of cardiovascular disease: population based, sibling controlled cohort study. BMJ 2019;365:l1255.
4. Friedman M, Rosenman RH, Carroll V. Changes in the serum cholesterol and blood-clotting time in men subjected to cyclic variation of occupational stress. Circulation 1958;17:852-61.
5. Thomas PD, Goodwin JM, Goodwin JS. Effect of social support on stress-related changes in cholesterol level, uric acid level, and immune function in an elderly sample. Am J Psychiatry 1985;142:735-7.
6. Grundy SM, Griffin AC: Effects of periodic mental stress on serum cholesterol levels. Circulation 1959;19:496-8.
7. Muldoon MF, Bachen EA, Manuck SB et al. Acute cholesterol responses to mental stress and change in posture. Arch Intern Med 1992;152:775-80.
8. Thrall G, Lane D, Carroll D, Lip GY. A systematic review of the effects of acute psychological stress and physical activity on haemorheology, coagulation, fibrinolysis and platelet reactivity: Implications for the pathogenesis of acute coronary syndromes. Thromb Res 2007;120:819-47.
Under the "diagnosis" heading the authors asserted that "hypothyroidism can be deemed the aetiology of pericardial effusion or cardiac tamponade if a high TSH level has been found, after excluding other secondary causes like a neoplastic, bacterial or an inflammatory process"(1).. I would add that, if the patient's hypothyroidism is of autoimmune aetiology, Addison's disease is a secondary cause that also requires urgent exclusion(2).
In one report, a 21 year old man presented with cardiac tamponade, in association with a TSH level of 17.9 microUnits/L(normal range 0.35-5.0 microUnits/L), and serum thyroxine and serum tri-iodothyronine levels which were both at the lower limit of the normal range. Serum cortisol, however, was 0.5 micrograms/dl(normal range 3.0-23.0 mcd/dl). Tests for thyroid and adrenal autoantibodies were positive, thereby fulfilling the criteria for Type 2 autoimmune polyglandular syndrome(Type-2 APS).
Comment
On the basis of the above observations the work-up of patients with pericardial effusion of presumed hypothyroid aetiology should include evaluation of adrenal function, because Addison's disease can, in its own right, be the underlying cause of cardiac tamponade(3). Furthermore, irrespective of hormonal status, pericardial effusion in a patient with Type 2 APS may ultimately be attributable to the "serositis" component of that syndrome, rendering the effusion capable of relapsing...
Under the "diagnosis" heading the authors asserted that "hypothyroidism can be deemed the aetiology of pericardial effusion or cardiac tamponade if a high TSH level has been found, after excluding other secondary causes like a neoplastic, bacterial or an inflammatory process"(1).. I would add that, if the patient's hypothyroidism is of autoimmune aetiology, Addison's disease is a secondary cause that also requires urgent exclusion(2).
In one report, a 21 year old man presented with cardiac tamponade, in association with a TSH level of 17.9 microUnits/L(normal range 0.35-5.0 microUnits/L), and serum thyroxine and serum tri-iodothyronine levels which were both at the lower limit of the normal range. Serum cortisol, however, was 0.5 micrograms/dl(normal range 3.0-23.0 mcd/dl). Tests for thyroid and adrenal autoantibodies were positive, thereby fulfilling the criteria for Type 2 autoimmune polyglandular syndrome(Type-2 APS).
Comment
On the basis of the above observations the work-up of patients with pericardial effusion of presumed hypothyroid aetiology should include evaluation of adrenal function, because Addison's disease can, in its own right, be the underlying cause of cardiac tamponade(3). Furthermore, irrespective of hormonal status, pericardial effusion in a patient with Type 2 APS may ultimately be attributable to the "serositis" component of that syndrome, rendering the effusion capable of relapsing or remitting irrespective of concurrent hormone replacement therapy(4).
An important caveat to interpretation of raised TSH levels is that, in the presence of primary hypoadrenalism, a raised serum TSH does not necessarily signify coexistence of primary hypothyroidism. On its own, primary hypoadrenalism can cause elevation of serum TSH which reverts to the normal range during the course of corticosteroid replacement therapy(5). In the latter report a 26 year old man with Addison's disease had a documented pretreatment serum TSH of 32 microUnits/L. Over a 2 year period of corticosteroid replacement therapy his serum TSH progressively fell to 2.5 microUnits/L, without concomitant thyroid replacement therapy. During that period both his serum thyroxine and serum tri-iodothyronine levels remained well within the normal range(5).
Finally, even in the presence of the coexistence of raised serum TSH and subnormal serum thyroxine clinicians should remain vigilant for type 2 APS, notwithstanding the fact that an identical biochemical scenario was depicted by the authors of the clinical vignette(1). In one case report a 24 year old man had a diagnosis of primary hypothyroidism characterised by serum thyroxine 40 nmol/L(normal 60-140 nmol/L), tri-iodothyronine 1.2 nmol/L(normal 1.6-3.0 nmol/L), and serum TSH 90 microUnits/L. However, he deteriorated after commencing thyroid replacement therapy, and this deterioration proved to be attributable to coexisting Addison's disease. Thyroxine was stopped, and he received corticosteroid replacement therapy instead. Over a period of 18 months of corticosteroid replacement therapy he experienced clinical improvement, and his thyroid function tests reverted to the normal range without the benefit of concomitant thyroid replacement therapy(6).
References
(1)Chahine J., Ala CK., Pantalone KM., Klein AL
Pericardial diseases in patients with hypothyroidism
Heart 2019;0:1-7,doi 10.1136/heartjnl-2018-314528
(2) Bacal A., Mathew G., Pyle J., Pauwaa S., Kazi M
Cardiac tamponade as initial presentation of autoimmune ployglandular syndrome type 2
AACE Clinical Case Reports 2018;4:e195-e198
(3) Torfoss D., von der Lippe E., Jacobsen D
Cardiac tamponade preceding adrenal insufficiency-an unusual presentation of Addison's disease: a report of two cases
Journal of Internal Medicine 1997;241:525-528
(4) Tucker WS., Niblack GD., McLean RH., Alspaught MA., Wyatt RJ., Jordan SC et al
Serositis with autoimmune endocrinopathy: Clinical and immunogenetic features
Medicine 1987;66:138-147
(5) Candrina R., Giustina G
Addison's disease and corticosteroid-reversible hypothyroidism
J Endocrinol Invest 1987;10:523-524
(6) Burrows AW
Reversible hypothyroidism after steroid replacement for Addison's disease
Postgrad Med J 1981;57:368-370
We read the article by Godino et al describing the risk of non-revascularisation of a coronary chronic total occlusion (CTO) for the cardiac death, sudden cardiac death and sustained ventricular arrhythmias (SCD/SVA) with great interest 1. After reading in detail, we have the following comments.
At first, although the authors mentioned a little in the DISCUSSION, the effect of medications for the prevention of cardiac death and SCD/SVA may better be clarified in the subjects. As they stated, because those who received CTO lesion revascularisation tend to have longer dual antiplatelet therapy and receive more hospital visit for follow-up coronary angiography to recheck, there might be such confounding factors. For example, the third generation P2Y12 class of adenosine diphosphate (ADP) receptors inhibitor was approved in 2009 in Europe 2. How was its distribution compared to conventional clopidogrel treatment? And appropriate statin treatment would be also associated with plaque stability and reduced cardiac adverse events as well as the beta-blocker administration for the prevention of SCD/SVA 3. Because the follow-up period was long as up to 12-years, the difference of these medication strategies between two groups should be clarified. The same also applies to the used stent types. The importance of current manuscript would be much better after these concerns were clarified.
Second, the multivariate analysis of Table 3 contains 2 factors,...
We read the article by Godino et al describing the risk of non-revascularisation of a coronary chronic total occlusion (CTO) for the cardiac death, sudden cardiac death and sustained ventricular arrhythmias (SCD/SVA) with great interest 1. After reading in detail, we have the following comments.
At first, although the authors mentioned a little in the DISCUSSION, the effect of medications for the prevention of cardiac death and SCD/SVA may better be clarified in the subjects. As they stated, because those who received CTO lesion revascularisation tend to have longer dual antiplatelet therapy and receive more hospital visit for follow-up coronary angiography to recheck, there might be such confounding factors. For example, the third generation P2Y12 class of adenosine diphosphate (ADP) receptors inhibitor was approved in 2009 in Europe 2. How was its distribution compared to conventional clopidogrel treatment? And appropriate statin treatment would be also associated with plaque stability and reduced cardiac adverse events as well as the beta-blocker administration for the prevention of SCD/SVA 3. Because the follow-up period was long as up to 12-years, the difference of these medication strategies between two groups should be clarified. The same also applies to the used stent types. The importance of current manuscript would be much better after these concerns were clarified.
Second, the multivariate analysis of Table 3 contains 2 factors, “CTO not revascularised” and “left ventricular ejection fraction (LVEF)”. However, from Table1, there was significant difference in left ventricular ejection fraction between CTO-R group and CTO-NR group. Thus, I suspect that these 2 factors, “CTO not revascularised” and “LVEF” may have significant multicollinearity. From the METHODS section, the authors wrote that comprehensive set of covariates, based on clinical relevance at univariate analysis and data from previous investigations were used. However, how did you exclude the multicollinearity? If you use the variance inflation factor (VIF), you may better present the VIF of enrolled variables. Because I guess if you include both CTO-NR and LVEF into multivariate analysis, CTO-NR may be excluded and only LVEF was preserved after step-wise method, i.e, the difference of the prognosis may be attributed to only LVEF difference.
Disclosures
The authors have no conflict of interest related to the manuscript.
Acknowledgements
None.
References
1 Godino C, Giannattasio A, Scotti A, et al. Risk of cardiac and sudden death with and without revascularisation of a coronary chronic total occlusion. Heart 2019 Feb 21. pii: heartjnl-2018-314076. doi: 10.1136/heartjnl-2018-314076.
2 Mousa SA, Jeske WP, Fareed J. Antiplatelet therapy prasugrel: a novel platelet ADP P2Y12 receptor antagonist. Clin Appl Thromb Hemost 2010 ;16:170-6.
3 Park JJ, Chae IH, Cho YS, et al. The recanalization of chronic total occlusion leads to lumen area increase in distal reference segments in selected patients: an intravascular ultrasound study. JACC Cardiovasc Interv 2012 ;5:827-36.
Editor, We agree with Lavie et al that the current standard model of delivering cardiac rehabilitation (CR) predominantly in hospital or centre based facilities has reached saturation and we should be looking at offering alternatives which could improve the global suboptimal rates of participation in CR. [1] Uptake of CR in heart failure remains particularly poor with rates of less than 20% in Europe. [2].
Clinicians and commissioners should consider implementing the findings of a UK based multicentre trial on home-based CR [3] which responds to the updated 2018 NICE guidance recommendation that adults with heart failure are offered a “..personalised, exercise-based CR programme – in a format and setting (at home, in the community or in the hospital) that is easily accessible” [https://www.nice.org.uk/guidance/ng106/chapter/Recommendations#cardiac-r... ]
We believe REACH HF to be the largest randomised trial of home based CR (co-developed by clinicians, academics, caregivers and patients) in heart failure with reduced ejection fraction and it provides important new evidence for a novel home-based CR programme in terms of benefit to patients and their caregivers. [3]
The results of the REACH HF trial show that it is possible to significantly improve patients’ health related quality of life and that the intervention has a cost of £418 per patient, within th...
Editor, We agree with Lavie et al that the current standard model of delivering cardiac rehabilitation (CR) predominantly in hospital or centre based facilities has reached saturation and we should be looking at offering alternatives which could improve the global suboptimal rates of participation in CR. [1] Uptake of CR in heart failure remains particularly poor with rates of less than 20% in Europe. [2].
Clinicians and commissioners should consider implementing the findings of a UK based multicentre trial on home-based CR [3] which responds to the updated 2018 NICE guidance recommendation that adults with heart failure are offered a “..personalised, exercise-based CR programme – in a format and setting (at home, in the community or in the hospital) that is easily accessible” [https://www.nice.org.uk/guidance/ng106/chapter/Recommendations#cardiac-r... ]
We believe REACH HF to be the largest randomised trial of home based CR (co-developed by clinicians, academics, caregivers and patients) in heart failure with reduced ejection fraction and it provides important new evidence for a novel home-based CR programme in terms of benefit to patients and their caregivers. [3]
The results of the REACH HF trial show that it is possible to significantly improve patients’ health related quality of life and that the intervention has a cost of £418 per patient, within the current NHS tariff of £477 for CR. [3]
Importantly, we have recently also demonstrated the long term cost effectiveness of home-based CR programmes like REACH HF in a cost effectiveness modelling analysis [4].This analysis shows that REACH-HF has an average cost per quality adjusted life year gained (QALY) of £1,720 with a 78% probability of being cost effective at the UK accepted threshold of £20,000/QALY gained. [4]
Home based CR programmes allow the delivery of care closer to where people need it and could also help towards achieving the ambitious target of offering CR to 85% of eligible patients set in the recently released NHS long-term plan (https://www.longtermplan.nhs.uk/online-version/chapter-3-further-progres...)
We believe that programmes, such as REACH-HF, can provide an affordable, cost effective CR intervention for service commissioners which can offset the current inequity in access to rehabilitation by patients with heart failure both in the UK and elsewhere.
Authors: Hasnain M Dalal (a, b), Rod S Taylor (a, c), Colin Greaves (d) and Patrick Doherty (e)
Affiliations:(a) Institute of Health Research, University of Exeter Medical School, Exeter, UK (b) Royal Cornwall Hospitals NHS Trust, Truro, UK (c) Institute of Health and Well Being, School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow and Institute of Health Research, University of Exeter Medical School, Exeter UK (d) School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, UK (e) Department of Health Sciences, University of York, York, UK
References
1. Lavie CJ, Kachur S and Milani R V. Making cardiac rehabilitation more available and affordable. Heart 2019; 105: 94–95. doi:10.1136/heartjnl-2018-313762
2. Bjarnason-Wehrens B, McGee H, Zwisler AD, Piepoli M, et al. Cardiac rehabilitation in Europe: results from the European Cardiac Rehabilitation Inventory Survey. Eur J Cardiovasc Prev Rehabil 2010;17:410-8. doi.org/10.1097/HJR.0b013e328334f42
3. Dalal HM, Taylor RS, Jolly K, et al. The effects and costs of home-based rehabilitation for heart failure with reduced ejection fraction: The REACH-HF multicentre randomized controlled trial. Eur J Prev Cardiol, Epub ahead of print 10 October 2018. doi.org/ 10.1177/2047487318806358.
4. Taylor RS, Sadler S, Dalal HM et al "The cost effectiveness of REACH-HF and home-based cardiac rehabilitation in the treatment of heart failure with reduced ejection fraction: a decision model-based analysis" Eur J Prev Cardiol, 2019 10.1177/2047487319833507 [In press, accepted 5.2.2019]
Given the fact that the entire purpose of blood pressure measurement is to identify the cut-off level of blood pressure that increases the risk for cerebral, cardiac, and renal events, and that "brachial blood pressure can be an imperfect surrogate for central aortic pressure"(1), the latter being independently correlated with incident cardiovascular disease and cardiovascular risk(2), the ultimate test of the utility of the novel cuffless device is the degree to which it deviates from central blood pressure. Only 33% of conventional brachial blood pressure values have been found to lie within 5 mm Hg below or above intra-arterial values(3). The other challenge is the validity of cuffless blood pressure measurements obtained from patients with atrial fibrillation
References
(1)Messerli F., Williams B., Ritz E
Essential hypertension
Lancet 2007;370:591-603
(2) Agabiti-Rosei E., Mancia G., O'Rourke MF et al
Cntral blood pressure measurements and antihypertensive therapy: A consensus statement
Hypertension 2007;50:154-160
(3)Manios E., Vemmos K., Tsivgoulis G et al
Comparison of noninvasive oscillometric and intraarterial blood pressure measurements in hyperacute stroke
Blood Press Monit 2007;12:149-156
Notwithstanding the high costs and lack of reimbursement associated with the use of positron emission tomography/computed tomography(PET/CT) in suspected cardiac implantable electronic device (CIED) infection(1), the ability of this modality to distinguish between infective and non infective vegetations is a powerful argument for its inclusion in the workup of suspected CIED. Evidence of the ability to make this distinction comes from two sources(2)(3). Firstly, in a retrospective study of 177 transoesophageal echocardiographic studies performed on 153 consecutive patients, a visible mass was observed on a device lead in 25 instances. In 11 studies this was a lead vegetation, in 13 instances only lead strands were seen, and in one instance a lead vegetation coexisted with a lead strand. Nevertheless, 18 of the 25 patients with lead-associated masses had no other evidence of infection. In that study the presence or absence of infection was adjudicated by three clinical investigators who independently reviewed all available clinical data without knowledge of the echocardiographic results(2). In another study, 63 consecutive patients(mean age 68.6) with suspected CIED were evaluated both by echocardiography(tranasthoracic and transoesophageal) and by PET/CT. Echocardiography was associated with a positive predictive value(PPV) of 83.3%, and a negative predictive value(NPV) of 69.2%. For PET/CT, PPV and NPV amounted to 100% and 93.9%, respectively(3). The additional ut...
Show MoreUnder the heading "Changes in kidney function during intercurrent illness"(1) mention must be made of the risk of acute kidney injury when nonsteroidal anti inflammatory drugs(NSAIDs) are prescribed for acute gout, the latter complication(the equivalent of "intercurrent illness") sometimes documented as a consequence of diuretic use in congestive heart failure(CHF)(2). Coprescription of NSAIDs, diuretics, and angiotensin converting enzyme inhibitors(or angiotensin receptor blockers), so-called triple therapy, is associated with increased risk of acute kidney injury(rate ratio 1.31, 95% Confidence Interval 1.12 to 1.53)(3). This was shown in a nested case-control study which enrolled patients in whom hypertension was the indication for prescription of diuretics and/or angiotensin converting enzyme inhibitors(or angiotensin receptor blockers)(3), but might be equally applicable in the context of CHF. Additionally, among CHF patients who have a drug regime which includes spironolactone, the use of NSAIDs might increase the risk of hyperkalaemia. The rationale is that NSAIDs "interfere with the stimulatory effect of prostaglandins on the release of renin"(4). The risk of hyperkalaemia may be compounded by concurrent use of beta adrenergic blocking agents(4).
Show MoreFor all the above reasons, NSAIDs should be contraindicated in CHF patients with gout. The recommended alternatives include colcichine(5) and intraarticuoar corticosteroids(6), resp...
We are grateful for the comments by David P Foley, Zoe Harcombe and Uffe Ravnsker on our paper.
Both American and UK guidelines for the treatment of cholesterol,[1,2] recommend monitoring percent reduction in low-density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. Our recently published paper [3] examined LDL-C reduction among patients initiating statins in the real-world setting.
With regard to the points raised:
Why didn’t you analyse the possible reasons for the observed ‘findings’?
Our study was not designed to establish causality so we are unable to analyse possible reasons for the observed findings. We are, however, undertaking further research to establish these latter.
Show MoreDavid P Foley notes in his response, ‘it is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect’. However, it is important to avoid any erroneous impression that patients are started on low dose statins in primary care. As shown in Table 1, most patients in this study were actually prescribed moderate and high potency statins (70.9% in the sub-optimal responders compared to 81.8% in the optimal responders).
A study by Vupputuri et al,[4] examined LDL-C reduction and adherence among high-risk patients initiating statins in a real-world setting using electronic health records of 1,066 patients in the US. Of patients with high adherence...
This study has already been inappropriately quoted in the media which is what the public read and misinformation is propagating. The authors need to take some responsibility for failing to point out that the dosing of the statins prescribed (most likely archaic low dose simvastatin) isn't analysed and long term compliance isn't addressed in this ' primary prevention population based longitudinal non interventional study'
Show MoreCardiologists are going to inundated with questions from patients with coronary disease on statins who have misinterpreted information which is incomplete and misrepresented - the title of the study needs to be highlighted 'Initiation of statins' is well put and needs to be remembered. The study cannot address the 'ongoing management' of cardiovascular risk with appropriate cardiovascular investigation of patients and optimization of preventative strategies as this study does not address this crucial aspect.
It is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect so that low doses initiated in general practice are actually ineffective and this is what the study shows NOT that statins are ineffective but that medical practice of blanket prescribing of low doses of statins is ineffective without monitoring of response and ongoing titration to achieve evidence based targets. This omission from the conclusions needs to be corrected and it ne...
The conclusion of this article was twofold: 1) approximately half of primary care patients put on statins did not achieve at least a 40% reduction in LDL-Cholesterol (the sub-optimal group) and 2) those who did (the optimal group) had fewer cardiovascular incidents over the next (approximately six) years.
Table 1 in the paper shows that the sub-optimal group have 1.43 times the “alcohol misuse” of the optimal group. There is no more information on alcohol consumption beyond this. Were the alcohol misusers also far less likely to be non or moderate drinkers and far more likely to be heavy and frequent drinkers?
The smoking information shows that, from the limited information available, the sub-optimal group were 25% more likely to be smokers. However, there is no smoking information for 96% of patients. There is no activity information – were the drinking/smokers more likely to be sedentary? Were they more likely to be obese?
There were more men in the sub-optimal group. The sub-optimal patients were more likely to be poorly-controlled diabetics and less likely to have hypertension treated.
Correspondence with the researchers confirmed that the HRs in Table 2 were not adjusted for anything other than age and baseline LDL-Cholesterol. They were not adjusted for alcohol misuse, or smoking, or gender, or any other lifestyle factors that were known to be different between the two groups – even with vast amounts of missing information.
The enti...
Show MoreIn their prospective cohort study of 165,411 primary care patients, Akyea et al. claim that suboptimal responders on statin treatment will experience significantly increased risk of future cardiovascular disease (CVD)(1). As many cardiovascular events may heal without serious health problems, we consider mortality as the most important outcome. Among the 80,802 patients with optimal cholesterol lowering, 821 (1.01 %) died from CVD. Among the 84,609 patients with suboptimal cholesterol-lowering 873 (1.03 %) died. This means that to prevent one cardiovascular death by optimal cholesterol lowering you have to increase the degree of lowering in 5,000 patients for six years. This is hardly a benefit because several independent researchers have reported that serious side effects from statin treatment are much more common than reported in the statin trials (2). The small numbers reported in the trial reports are achieved by excluding participants who suffer from side effects of the drug during a few weeks long run-in period before the start of the trial. That this is an effective method to lower the number of side effects appeared in the IDEAL trial where this method wasn´t used and where a high statin dose was compared with a low dose, because in that trial almost half of the participants in both groups suffered from serious side effects (2).
Furthermore, Akyea et al. have not reported total mortality in the two groups. This failure may introduce another bias because tota...
Show MoreUnder the "diagnosis" heading the authors asserted that "hypothyroidism can be deemed the aetiology of pericardial effusion or cardiac tamponade if a high TSH level has been found, after excluding other secondary causes like a neoplastic, bacterial or an inflammatory process"(1).. I would add that, if the patient's hypothyroidism is of autoimmune aetiology, Addison's disease is a secondary cause that also requires urgent exclusion(2).
Show MoreIn one report, a 21 year old man presented with cardiac tamponade, in association with a TSH level of 17.9 microUnits/L(normal range 0.35-5.0 microUnits/L), and serum thyroxine and serum tri-iodothyronine levels which were both at the lower limit of the normal range. Serum cortisol, however, was 0.5 micrograms/dl(normal range 3.0-23.0 mcd/dl). Tests for thyroid and adrenal autoantibodies were positive, thereby fulfilling the criteria for Type 2 autoimmune polyglandular syndrome(Type-2 APS).
Comment
On the basis of the above observations the work-up of patients with pericardial effusion of presumed hypothyroid aetiology should include evaluation of adrenal function, because Addison's disease can, in its own right, be the underlying cause of cardiac tamponade(3). Furthermore, irrespective of hormonal status, pericardial effusion in a patient with Type 2 APS may ultimately be attributable to the "serositis" component of that syndrome, rendering the effusion capable of relapsing...
To the Editor
We read the article by Godino et al describing the risk of non-revascularisation of a coronary chronic total occlusion (CTO) for the cardiac death, sudden cardiac death and sustained ventricular arrhythmias (SCD/SVA) with great interest 1. After reading in detail, we have the following comments.
Show MoreAt first, although the authors mentioned a little in the DISCUSSION, the effect of medications for the prevention of cardiac death and SCD/SVA may better be clarified in the subjects. As they stated, because those who received CTO lesion revascularisation tend to have longer dual antiplatelet therapy and receive more hospital visit for follow-up coronary angiography to recheck, there might be such confounding factors. For example, the third generation P2Y12 class of adenosine diphosphate (ADP) receptors inhibitor was approved in 2009 in Europe 2. How was its distribution compared to conventional clopidogrel treatment? And appropriate statin treatment would be also associated with plaque stability and reduced cardiac adverse events as well as the beta-blocker administration for the prevention of SCD/SVA 3. Because the follow-up period was long as up to 12-years, the difference of these medication strategies between two groups should be clarified. The same also applies to the used stent types. The importance of current manuscript would be much better after these concerns were clarified.
Second, the multivariate analysis of Table 3 contains 2 factors,...
Editor, We agree with Lavie et al that the current standard model of delivering cardiac rehabilitation (CR) predominantly in hospital or centre based facilities has reached saturation and we should be looking at offering alternatives which could improve the global suboptimal rates of participation in CR. [1] Uptake of CR in heart failure remains particularly poor with rates of less than 20% in Europe. [2].
Show MoreClinicians and commissioners should consider implementing the findings of a UK based multicentre trial on home-based CR [3] which responds to the updated 2018 NICE guidance recommendation that adults with heart failure are offered a “..personalised, exercise-based CR programme – in a format and setting (at home, in the community or in the hospital) that is easily accessible” [https://www.nice.org.uk/guidance/ng106/chapter/Recommendations#cardiac-r... ]
We believe REACH HF to be the largest randomised trial of home based CR (co-developed by clinicians, academics, caregivers and patients) in heart failure with reduced ejection fraction and it provides important new evidence for a novel home-based CR programme in terms of benefit to patients and their caregivers. [3]
The results of the REACH HF trial show that it is possible to significantly improve patients’ health related quality of life and that the intervention has a cost of £418 per patient, within th...
Given the fact that the entire purpose of blood pressure measurement is to identify the cut-off level of blood pressure that increases the risk for cerebral, cardiac, and renal events, and that "brachial blood pressure can be an imperfect surrogate for central aortic pressure"(1), the latter being independently correlated with incident cardiovascular disease and cardiovascular risk(2), the ultimate test of the utility of the novel cuffless device is the degree to which it deviates from central blood pressure. Only 33% of conventional brachial blood pressure values have been found to lie within 5 mm Hg below or above intra-arterial values(3). The other challenge is the validity of cuffless blood pressure measurements obtained from patients with atrial fibrillation
References
(1)Messerli F., Williams B., Ritz E
Essential hypertension
Lancet 2007;370:591-603
(2) Agabiti-Rosei E., Mancia G., O'Rourke MF et al
Cntral blood pressure measurements and antihypertensive therapy: A consensus statement
Hypertension 2007;50:154-160
(3)Manios E., Vemmos K., Tsivgoulis G et al
Comparison of noninvasive oscillometric and intraarterial blood pressure measurements in hyperacute stroke
Blood Press Monit 2007;12:149-156
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