In this article, the authors follow a very ambitious objective: to refute the LDL central role in atherosclerosis paradigm. There is an ironic statement that quotes: if you point to the King, be sure not to leave him alive. Here I’m afraid this article leaves the King alive because the methodology chose had inferior quality of evidence in relation to a well-done metanalisys like –for example- the one which was published by the Cholesterol Treatment Trialist (CTT).
In order to the studies included in this selection there were some inconsistencies. First of all, the WOSCOPS trial and the AFCAPS/TexCAPS trial were used to analyze the effect of a reduction at least of 30% in LDL but these two pivotal articles showed a reduction of 20% and 25%, respectively. In fact, in the pilots’ study there were only 157 deaths from 6605 patients randomized so the study hadn’t enough statistical power to analyze the mortality endpoint. In the same direction, the selection of the SEAS study was controversial because in spite of achieves a 61% reduction in LDL, the population included hadn’t a clear indication of statin treatment in relation of ethical considerations, affecting the results in order to MACE and mortality. Also it was very polemical to include trials as SHARP or AURORA with patients on dialysis because we know this kind of treatment actives a lot of mechanisms of morbidity and mortality with independence of the LDL level. Other weak point is to analyze mortality taking in...
In this article, the authors follow a very ambitious objective: to refute the LDL central role in atherosclerosis paradigm. There is an ironic statement that quotes: if you point to the King, be sure not to leave him alive. Here I’m afraid this article leaves the King alive because the methodology chose had inferior quality of evidence in relation to a well-done metanalisys like –for example- the one which was published by the Cholesterol Treatment Trialist (CTT).
In order to the studies included in this selection there were some inconsistencies. First of all, the WOSCOPS trial and the AFCAPS/TexCAPS trial were used to analyze the effect of a reduction at least of 30% in LDL but these two pivotal articles showed a reduction of 20% and 25%, respectively. In fact, in the pilots’ study there were only 157 deaths from 6605 patients randomized so the study hadn’t enough statistical power to analyze the mortality endpoint. In the same direction, the selection of the SEAS study was controversial because in spite of achieves a 61% reduction in LDL, the population included hadn’t a clear indication of statin treatment in relation of ethical considerations, affecting the results in order to MACE and mortality. Also it was very polemical to include trials as SHARP or AURORA with patients on dialysis because we know this kind of treatment actives a lot of mechanisms of morbidity and mortality with independence of the LDL level. Other weak point is to analyze mortality taking into account studies that not official report it as ODYSSEY long Term and ODYSSEY COMBO I.
On the other hand, this article enlists essays in secondary prevention like FOURIER or IMPROVE-IT but it doesn’t include the HPS –with its huge statistical weight- or PROSPER –which achieves minor coronary death in elderly patients- or PROVE-IT or TNT. This situation looks like a whimsical selection without a solid support instead of a consistent piece of evidence.
I believe LDL central role in atherosclerosis is not quit questionable as the methodology used to calculate cardiovascular risk on primary prevention population or the residual risk in patients with prior heart disease. In my opinion, this would allow us to take the cardiovascular disease as the first cause of death of the world.
In this article, the authors follow a very ambitious objective: to refute the LDL central role in atherosclerosis paradigm. There is an ironic statement that quotes: if you point to the King, be sure not to leave him alive. Here I’m afraid this article leaves the King alive because the methodology chose had inferior quality of evidence in relation to a well-done metanalisys like –for example- the one which was published by the Cholesterol Treatment Trialist (CTT).
In order to the studies included in this selection there were some inconsistencies. First of all, the WOSCOPS trial and the AFCAPS/TexCAPS trial were used to analyze the effect of a reduction at least of 30% in LDL but these two pivotal articles showed a reduction of 20% and 25%, respectively. In fact, in the pilots’ study there were only 157 deaths from 6605 patients randomized so the study hadn’t enough statistical power to analyze the mortality endpoint. In the same direction, the selection of the SEAS study was controversial because in spite of achieves a 61% reduction in LDL, the population included hadn’t a clear indication of statin treatment in relation of ethical considerations, affecting the results in order to MACE and mortality. Also it was very polemical to include trials as SHARP or AURORA with patients on dialysis because we know this kind of treatment actives a lot of mechanisms of morbidity and mortality with independence of the LDL level. Other weak point is to analyze mortality taking in...
In this article, the authors follow a very ambitious objective: to refute the LDL central role in atherosclerosis paradigm. There is an ironic statement that quotes: if you point to the King, be sure not to leave him alive. Here I’m afraid this article leaves the King alive because the methodology chose had inferior quality of evidence in relation to a well-done metanalisys like –for example- the one which was published by the Cholesterol Treatment Trialist (CTT).
In order to the studies included in this selection there were some inconsistencies. First of all, the WOSCOPS trial and the AFCAPS/TexCAPS trial were used to analyze the effect of a reduction at least of 30% in LDL but these two pivotal articles showed a reduction of 20% and 25%, respectively. In fact, in the pilots’ study there were only 157 deaths from 6605 patients randomized so the study hadn’t enough statistical power to analyze the mortality endpoint. In the same direction, the selection of the SEAS study was controversial because in spite of achieves a 61% reduction in LDL, the population included hadn’t a clear indication of statin treatment in relation of ethical considerations, affecting the results in order to MACE and mortality. Also it was very polemical to include trials as SHARP or AURORA with patients on dialysis because we know this kind of treatment actives a lot of mechanisms of morbidity and mortality with independence of the LDL level. Other weak point is to analyze mortality taking into account studies that not official report it as ODYSSEY long Term and ODYSSEY COMBO I.
On the other hand, this article enlists essays in secondary prevention like FOURIER or IMPROVE-IT but it doesn’t include the HPS –with its huge statistical weight- or PROSPER –which achieves minor coronary death in elderly patients- or PROVE-IT or TNT. This situation looks like a whimsical selection without a solid support instead of a consistent piece of evidence.
I believe LDL central role in atherosclerosis is not quit questionable as the methodology used to calculate cardiovascular risk on primary prevention population or the residual risk in patients with prior heart disease. In my opinion, this would allow us to take the cardiovascular disease as the first cause of death of the world.
I read with interest the latest evidence for honey and treatment of coughs which was also reported widely in the national press (1). Honey has been shown in laboratory in vitro studies to inhibit bacterial growth including Helicobacter pylori linked with dyspepsia and gastritis (2, 3). Concentrations between 10-20% honey has been shown to be effective against both Gram negative and Gram positive bacteria (3). My late father Professor MNH Chowdhury, a clinical bacteriologist, researched this in the 1990s and advocated Manuka honey especially for its healing and antibacterIal properties. Interestingly, the in vitro findings showed some isolates were resistant to various antimicrobial agents but honey inhibited these organisms also (3). Secondary bacterial infections may respond to this simple remedy after primary viral coughs and colds and need further clinical study.
References
1. Abuelgasim H, Albury C, Lee J. Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis. BMJ Evidence Based Med 2020, 18 Aug online; bmjebm-2020-111336.
2. Rashed RS, Ayoola EA, Mofleh IA, Chowdhury MNH, Mahmood K, Faleh FZ. Helicobacter pylori and dyspepsia in an Arab population. Trop Geogr Med 1992; 44(4), 304-7.
3. Ali AT, Chowdhury MNH, al Humayyad MS. Inhibitory effect of natural honey on Helicobacter pylori. Trop Gastroenterol 1991; 12(3), 139-43.
It is risky to propose that agent offering symptomatic relief should replace microbial cure. Two are different aspects and different approaches.
Besides honey may not be considered entirely safe. Many environmental Journals are raising voice against contamination of honey either by microbes or by antimicrobials.
Clinicians must know if the Upper Respiratory Infection is going to be entirely selflimited and will not progress to Pneumonia, or lead to late Sequelae like Rheumatic Fever Rheumatic Heart Disease.
If only symptomatic relief is to be achieved, one wonders if home made sugar syrup may work as well as honey will. Moreover homemade sugar syrup will not carry microbes or antimicrobials!
Arvind Joshi MBBS MD FCGP FAMS FICP.
The Editor
Read with interest the article
" Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis"
Symptomatic relief and treatment of infections are entirely different treatment goals.
A clinician must decide very clearly either on clinical grounds or with investigations, if the infection is going to be a selflimited one which will subside completely without any antimicrobial and also will not cause any late Sequelae. A very important example in this regards used to be Streptococcal throat infections which often would subside without proper antimicrobial treatment, only to cause Rheumatic Fever, Rheumatic Arthritis and Rheumatic Heart Disease later. Not necessarily upper respiratory tract infections, post Streptococcal Glomerulonephritis, post Rickettsial complications are some of the examples where not symptomatic relief, but prompt and adequuate treatment of infections with antimicrobials is crucial for preventing devastating Sequelae.
It is often very difficult to to foresee which respiratory or for that matter any infection will be self limited and will not cause any serious Sequelae if no antimicrobials are used.
That is the CATCH!
Arvind Joshi;
MBBS, MD; FCGP, FAMS;
Founder Convener and President:
Our Own Discussion Group,
602-C, Megh Apartments,
Ganesh Peth Lane, Dadar West;
Mumbai PIN 400028;
Consaltant...
The Editor
Read with interest the article
" Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis"
Symptomatic relief and treatment of infections are entirely different treatment goals.
A clinician must decide very clearly either on clinical grounds or with investigations, if the infection is going to be a selflimited one which will subside completely without any antimicrobial and also will not cause any late Sequelae. A very important example in this regards used to be Streptococcal throat infections which often would subside without proper antimicrobial treatment, only to cause Rheumatic Fever, Rheumatic Arthritis and Rheumatic Heart Disease later. Not necessarily upper respiratory tract infections, post Streptococcal Glomerulonephritis, post Rickettsial complications are some of the examples where not symptomatic relief, but prompt and adequuate treatment of infections with antimicrobials is crucial for preventing devastating Sequelae.
It is often very difficult to to foresee which respiratory or for that matter any infection will be self limited and will not cause any serious Sequelae if no antimicrobials are used.
That is the CATCH!
Arvind Joshi;
MBBS, MD; FCGP, FAMS;
Founder Convener and President:
Our Own Discussion Group,
602-C, Megh Apartments,
Ganesh Peth Lane, Dadar West;
Mumbai PIN 400028;
Consaltant Physician at Ruchi Diagnostic Center and Ruchi Clinical Laboratory, Sunshine CHS, Plot 58,
Kharghar PIN 410210,
Maharashtra State, INDIA.
FICP
Might it be helpful to clarify in the title or abstract that the paper relates solely to estrogen containing contraceptives, and essentially the oral versions?
In a systematic review of cholesterol reduction clinical trials, DuBroff et al claimed that “the evidence presented challenges cardiovascular disease prevention through targeted reductions of LDL-cholesterol”. However, it should be noted that the concept authors claim to challenge has never been proved, nor properly tested (1). This raises the question of whether there is a need to disprove an unproven concept. In science, the burden is on the proof.
Nevertheless, if it was to disprove, we must recognize the limitations of the present study. Regarding testing "the target paradigm", the authors first categorized the trials as to whether they did or did not meet average LDL-cholesterol reduction recommended by AHA/ACC 2018 guidelines (2) for individuals. Then, they intended to test the association between reaching this arbitrary target (suggested by one specific guideline) with the trial being positive or negative regarding death or cardiovascular events. However, no statistical inference was performed for this main analysis and no significance level was presented for the interaction between reaching the target and having clinical benefit. Instead, in this systematic review that intended to test a hypothesis that implied interaction phenomenon, the authors "intentionally did not perform a meta-analysis" under the justification that trials “involved three different drug classes”.
Finally, as the authors noted, it was a systematic review of s...
In a systematic review of cholesterol reduction clinical trials, DuBroff et al claimed that “the evidence presented challenges cardiovascular disease prevention through targeted reductions of LDL-cholesterol”. However, it should be noted that the concept authors claim to challenge has never been proved, nor properly tested (1). This raises the question of whether there is a need to disprove an unproven concept. In science, the burden is on the proof.
Nevertheless, if it was to disprove, we must recognize the limitations of the present study. Regarding testing "the target paradigm", the authors first categorized the trials as to whether they did or did not meet average LDL-cholesterol reduction recommended by AHA/ACC 2018 guidelines (2) for individuals. Then, they intended to test the association between reaching this arbitrary target (suggested by one specific guideline) with the trial being positive or negative regarding death or cardiovascular events. However, no statistical inference was performed for this main analysis and no significance level was presented for the interaction between reaching the target and having clinical benefit. Instead, in this systematic review that intended to test a hypothesis that implied interaction phenomenon, the authors "intentionally did not perform a meta-analysis" under the justification that trials “involved three different drug classes”.
Finally, as the authors noted, it was a systematic review of studies not suited to test the paradigm of targets. The primary test for this hypothesis should be the randomization of patients to have drug doses adjusted to a target goal or to have a fixed dose.
In fact, a proper conclusion of a systematic review that aimed to “test the validity of this [target] paradigm” would be for absence of evidence, instead of claiming evidence of absence by very limited data analysis against a unproven concept.
That being said, the value of using LDL-cholesterol targets has never been demonstrated, nor should be reinforced by guidelines.
2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2019 Jun 18;139(25):e1182-e1186]. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/CIR.0000000000000625
Like so many purported pundits, DuBroff R, de Lorgeril M [1] have attempted to dispute the significance of the role of saturated fat (triglycerides) and LDL-cholesterol in the development of coronary artery disease, while noting the importance of inflammation itself [1,2]. In law, ignorance of the law is not a defense - the same is true for medicine. Not understanding something does not make you an expert [2] and it does not make your argument valid. Appealing to the court of public opinion does not make it so either. Accordingly, we present a brief explanation of why the authors [1,2] – and others – have presented an invalid discussion of the role fat and LDL-cholesterol plays in coronary artery disease.
In the mid-1990s, as one of the reviewers for the American Heart Association, the first author of this letter, Dr Richard M Fleming (RMF) introduced a then controversial theory stating that Coronary Artery Disease (CAD) is the result of an inflammatory process, which builds up within the walls of the arteries impairing their ability to dilate and increase coronary blood flow when needed; thus producing regional blood flow differences resulting in angina [3-6] and ultimately myocardial infarction (MI) and death.
In recent years, people promoting various dietary and lifestyle practices – particularly those promoting LowCarb-Keto diets, have used the obesity epidemic to focus attention on obesity and weight loss. These same individuals have not demonstrated th...
Like so many purported pundits, DuBroff R, de Lorgeril M [1] have attempted to dispute the significance of the role of saturated fat (triglycerides) and LDL-cholesterol in the development of coronary artery disease, while noting the importance of inflammation itself [1,2]. In law, ignorance of the law is not a defense - the same is true for medicine. Not understanding something does not make you an expert [2] and it does not make your argument valid. Appealing to the court of public opinion does not make it so either. Accordingly, we present a brief explanation of why the authors [1,2] – and others – have presented an invalid discussion of the role fat and LDL-cholesterol plays in coronary artery disease.
In the mid-1990s, as one of the reviewers for the American Heart Association, the first author of this letter, Dr Richard M Fleming (RMF) introduced a then controversial theory stating that Coronary Artery Disease (CAD) is the result of an inflammatory process, which builds up within the walls of the arteries impairing their ability to dilate and increase coronary blood flow when needed; thus producing regional blood flow differences resulting in angina [3-6] and ultimately myocardial infarction (MI) and death.
In recent years, people promoting various dietary and lifestyle practices – particularly those promoting LowCarb-Keto diets, have used the obesity epidemic to focus attention on obesity and weight loss. These same individuals have not demonstrated the actual impact their diets have on CAD, anymore than BigPharma has by reporting changes in lipid levels using their drugs. To demonstrate such change in CAD - either by drug or dietary intervention - requires more than the mere showing of changes in weight or serum blood tests as discussed infra. It requires the actual measurement of the changes occurring within the walls of the coronary arteries themselves – not some other artery – where the actual inflammation and resulting change in coronary artery function exists [3,6].
The arguments presented by DuBroff [1] and Ravnskov [2] erroneously use studies measuring lipid and inflammatory surrogate markers - blood tests - to support their position, while others [7] use this same approach to support their dietary recommendations by showing weight loss, and occasionally reductions in cholesterol levels – at least initially in some people. As more studies have been done, it has been shown that these initial reductions in lipid levels either do not occur for everyone or are followed by a subsequent increase. This has forced the purported diet pundits to support the position that LDL-cholesterol and saturated (triglycerides) fat do not clog the (coronary or other) arteries [7].
For the authors [1,2,7] to declare that saturated fat and LDL-cholesterol have nothing to do with the development of inflammatory CAD demonstrates a complete failure to understand the “Inflammation and Heart Disease” Theory [5,8], or a failure to have read it, and therefore cannot be taken seriously.
The specific claims made by Malhotra [7] introduces yet another major misconception into the discussion of CAD. Specifically, the process of “clogging of the coronary arteries.” The narrowing or “clogging” of the coronary artery lumen – where the blood flows - so frequently referred to as CAD, is actually a late process in the development of the inflammatory changes that are CAD [9-15].
CAD begins with an inflammatory process, which first distends the wall of the artery outward away from the lumen – impairing the function of the artery - and only later encroaches upon the coronary lumen itself [3,5,9]. Recognition that the rupture of this inflammatory process may occur following minimal or no coronary lumen narrowing [3-5,9] has resulted in the recent acknowledgement by the Cardiology community that infarction of myocardium may occur with (Type I) or without (TYPE II) coronary lumen obstruction.
Fleming and Harrington’s research published in 2008 [16] demonstrated that the relationship between weight loss, and changes in lipids and other blood tests reflecting inflammatory processes [5], are only mildly-to-moderately correlated with actual changes occurring within the coronary arteries themselves. Thus further exposing the erroneous artery “clogging” statement - using the results of blood tests – to declare that saturated fat and cholesterol are not involved in CAD.
To understand the impact LowCarb-Keto diets - or for that matter any diet or drug treatment - has on CAD, one needs to measure what is actually happening to the coronary arteries themselves [17-19]; quantitatively now made possible using FMTVDM [6].
To state that Saturated fat and LDL-cholesterol has nothing to do with CAD and do not result in the “clogging” of coronary arteries or CAD itself, and then to state that CAD is a chronic inflammatory condition - raises serious concerns about the motivation and integrity of their arguments. It also raises serious questions about their actual understanding of the ”Inflammation and Heart Disease” and “Angina” Theories [3,5,20]. Ignorance is not bliss - “we can teach it to you, but we cannot understand it for you.”
We are sadly reminded of these words from Billy Madison:
“Mr. Madison, what you just said is one of the most insanely idiotic things I have ever heard. At no point in your rambling incoherent response were you even close to anything that could be considered a rational thought. Everyone in this room is now dumber for having listened to it. I award you no points and may God have mercy on your soul.”
Acknowledged potential COI: FMTVDM (The Fleming Method for Tissue and Vascular Differentiation and Metabolism) [6] is issued to the first author. The first author authored the “Inflammation and Heart Disease” and “Angina” Theories.
References:
1. DuBroff R, de Lorgeril M. Fat or fiction: the diet-heart hypothesis. BMJ Evidence-Based Medicine 2019 doi:10.1136/bmjebm-2019-111180.
2. Ravnskov U, de Lorgeril M, Diamond DM, et al. LDL-C does not cause cardiovascular disease: a comprehensive review off the current literature. Expert review of clinical pharmacology
3. Fleming RM. Chapter 29. Atherosclerosis: Understanding the relationship between coronary artery disease and stenosis flow reserve. Textbook of Angiology. John C. Chang Editor, Springer-Verlag, New York, NY. 1999. pp. 381-387.
4. Fleming RM. Chapter 30. Cholesterol, Triglycerides and the treatment of hyperlipidemias. Textbook of Angiology. John C. Chang Editor, Springer-Verlag, New York, NY. 1999, pp. 388-396.
5. Fleming RM. Chapter 64. The Pathogenesis of Vascular Disease. Textbook of Angiology. John C. Chang Editor, Springer-Verlag New York, NY. 1999, pp. 787-798.
6. The Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) using same state single or sequential quantification comparisons. Patent Number 9566037. Issued 02/14/2017.
7. Malhotra A, Redberg R, Meier P. Saturated fat does not clog the arteries: coronary heart disease is a chronic inflammatory condition, the risk of which can be effectively reduced from healthy lifestyle interventions. British J Sports Med 2017;51:1111-1112.
8. 20/20 Segment on Heart Disease and Inflammation. https://www.youtube.com/watch?v=Hvb_Ced7KyA&t=22s
9. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316(22):1371-1375.
10. Fleming RM., Kirkeeide RL, Smalling RW, Gould KL. Patterns in Visual Interpretation of Coronary Arteriograms as Detected by Quantitative Coronary Arteriography. J Am Coll. Cardiol. 1991;18:945- 951.
11. Fleming RM, Harrington GM. Quantitative Coronary Arteriography and its Assessment of Atherosclerosis. Part 1. Examining the Independent Variables. Angiology 1994;45(10):829-833.
12. Fleming RM, Harrington GM. Quantitative Coronary Arteriography and its Assessment of Atherosclerosis. Part 2. Calculating Stenosis Flow Reserve Directly from Percent Diameter Stenosis. Angiology 1994;45(10):835-840.
13. Fleming RM. Shortcomings of coronary angiography. Letter to the Editor. Cleve Clin J Med 2000;67:450.
14. Fleming RM. Coronary Artery Disease is More than Just Coronary Lumen Disease. Amer J Card 2001;88:599-600.
15. Fleming RM, Harrington GM. TAM-A.7 Sestamibi redistribution measurement defines ischemic coronary artery lumen disease. 56th Annual Meeting of the Health Physics Society. (American Conference of Radiological Safety) West Palm Beach, FL, USA, 30 June 2011. http://hpschapters.org/2011AM/program/singlesession.php3?sessid=TAM-A
16. Fleming RM, Harrington GM. What is the Relationship between Myocardial Perfusion Imaging and Coronary Artery Disease Risk Factors and Markers of Inflammation? Angiology 2008;59:16-25.
17. Fleming RM, Fleming MR, Chaudhuri TK. Replacing Cardiovascular Risk Factors with True AI and Absolute Quantifiable Measurement (FMTVDM) of Coronary Artery Disease. Inter J Res Studies Med & Health Sci. 2019;4(11):11- 13. ISSN:2456-6373.
18. Fleming RM, Fleming MR, Chaudhuri TK. Are we prescribing the right diets and drugs for CAD, T2D, Cancer and Obesity? Int J Nuclear Med Radioactive Subs 2019;2(2):000115.
19. Fleming RM, Fleming MR, Chaudhuri TK, Harrington GM. Cardiovascular Outcomes of Diet Counseling. Edel J Biomed Res Rev. 2019;1(1):20-29.
20. Fleming RM., Boyd L., Forster M. Angina is Caused by Regional Blood Flow Differences - Proof of a Physiologic (Not Anatomic) Narrowing, Joint Session of the European Society of Cardiology and the American College of Cardiology, Annual American College of Cardiology Scientific Sessions, Anaheim, California, USA, 12 March 2000, 49th (Placed on internet www.prous.com for physician training and CME credit, April 2000.)
Thank you for this measured summary of the recently published HYGIA trial. I am pleased to see you mention the BedMed study ongoing. Readers may be interested to know that there is another study, already in follow-up, which will provide further evidence on whether night-time dosing of blood pressure medications really is better in the prevention of cardiovascular events and mortality.
The University of Dundee's Treatment in Morning vs Evening (TIME, www.timestudy.co.uk) study, funded by the British Heart Foundation, aims to answer the same research question. TIME has recruited 21,104 participants across the UK and should finish in the first half of 2020.
In this article, the authors follow a very ambitious objective: to refute the LDL central role in atherosclerosis paradigm. There is an ironic statement that quotes: if you point to the King, be sure not to leave him alive. Here I’m afraid this article leaves the King alive because the methodology chose had inferior quality of evidence in relation to a well-done metanalisys like –for example- the one which was published by the Cholesterol Treatment Trialist (CTT).
Show MoreIn order to the studies included in this selection there were some inconsistencies. First of all, the WOSCOPS trial and the AFCAPS/TexCAPS trial were used to analyze the effect of a reduction at least of 30% in LDL but these two pivotal articles showed a reduction of 20% and 25%, respectively. In fact, in the pilots’ study there were only 157 deaths from 6605 patients randomized so the study hadn’t enough statistical power to analyze the mortality endpoint. In the same direction, the selection of the SEAS study was controversial because in spite of achieves a 61% reduction in LDL, the population included hadn’t a clear indication of statin treatment in relation of ethical considerations, affecting the results in order to MACE and mortality. Also it was very polemical to include trials as SHARP or AURORA with patients on dialysis because we know this kind of treatment actives a lot of mechanisms of morbidity and mortality with independence of the LDL level. Other weak point is to analyze mortality taking in...
In this article, the authors follow a very ambitious objective: to refute the LDL central role in atherosclerosis paradigm. There is an ironic statement that quotes: if you point to the King, be sure not to leave him alive. Here I’m afraid this article leaves the King alive because the methodology chose had inferior quality of evidence in relation to a well-done metanalisys like –for example- the one which was published by the Cholesterol Treatment Trialist (CTT).
Show MoreIn order to the studies included in this selection there were some inconsistencies. First of all, the WOSCOPS trial and the AFCAPS/TexCAPS trial were used to analyze the effect of a reduction at least of 30% in LDL but these two pivotal articles showed a reduction of 20% and 25%, respectively. In fact, in the pilots’ study there were only 157 deaths from 6605 patients randomized so the study hadn’t enough statistical power to analyze the mortality endpoint. In the same direction, the selection of the SEAS study was controversial because in spite of achieves a 61% reduction in LDL, the population included hadn’t a clear indication of statin treatment in relation of ethical considerations, affecting the results in order to MACE and mortality. Also it was very polemical to include trials as SHARP or AURORA with patients on dialysis because we know this kind of treatment actives a lot of mechanisms of morbidity and mortality with independence of the LDL level. Other weak point is to analyze mortality taking in...
I read with interest the latest evidence for honey and treatment of coughs which was also reported widely in the national press (1). Honey has been shown in laboratory in vitro studies to inhibit bacterial growth including Helicobacter pylori linked with dyspepsia and gastritis (2, 3). Concentrations between 10-20% honey has been shown to be effective against both Gram negative and Gram positive bacteria (3). My late father Professor MNH Chowdhury, a clinical bacteriologist, researched this in the 1990s and advocated Manuka honey especially for its healing and antibacterIal properties. Interestingly, the in vitro findings showed some isolates were resistant to various antimicrobial agents but honey inhibited these organisms also (3). Secondary bacterial infections may respond to this simple remedy after primary viral coughs and colds and need further clinical study.
References
1. Abuelgasim H, Albury C, Lee J. Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis. BMJ Evidence Based Med 2020, 18 Aug online; bmjebm-2020-111336.
2. Rashed RS, Ayoola EA, Mofleh IA, Chowdhury MNH, Mahmood K, Faleh FZ. Helicobacter pylori and dyspepsia in an Arab population. Trop Geogr Med 1992; 44(4), 304-7.
3. Ali AT, Chowdhury MNH, al Humayyad MS. Inhibitory effect of natural honey on Helicobacter pylori. Trop Gastroenterol 1991; 12(3), 139-43.
It is risky to propose that agent offering symptomatic relief should replace microbial cure. Two are different aspects and different approaches.
Besides honey may not be considered entirely safe. Many environmental Journals are raising voice against contamination of honey either by microbes or by antimicrobials.
Clinicians must know if the Upper Respiratory Infection is going to be entirely selflimited and will not progress to Pneumonia, or lead to late Sequelae like Rheumatic Fever Rheumatic Heart Disease.
If only symptomatic relief is to be achieved, one wonders if home made sugar syrup may work as well as honey will. Moreover homemade sugar syrup will not carry microbes or antimicrobials!
Arvind Joshi MBBS MD FCGP FAMS FICP.
The Editor
Show MoreRead with interest the article
" Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis"
Symptomatic relief and treatment of infections are entirely different treatment goals.
A clinician must decide very clearly either on clinical grounds or with investigations, if the infection is going to be a selflimited one which will subside completely without any antimicrobial and also will not cause any late Sequelae. A very important example in this regards used to be Streptococcal throat infections which often would subside without proper antimicrobial treatment, only to cause Rheumatic Fever, Rheumatic Arthritis and Rheumatic Heart Disease later. Not necessarily upper respiratory tract infections, post Streptococcal Glomerulonephritis, post Rickettsial complications are some of the examples where not symptomatic relief, but prompt and adequuate treatment of infections with antimicrobials is crucial for preventing devastating Sequelae.
It is often very difficult to to foresee which respiratory or for that matter any infection will be self limited and will not cause any serious Sequelae if no antimicrobials are used.
That is the CATCH!
Arvind Joshi;
MBBS, MD; FCGP, FAMS;
Founder Convener and President:
Our Own Discussion Group,
602-C, Megh Apartments,
Ganesh Peth Lane, Dadar West;
Mumbai PIN 400028;
Consaltant...
Might it be helpful to clarify in the title or abstract that the paper relates solely to estrogen containing contraceptives, and essentially the oral versions?
In a systematic review of cholesterol reduction clinical trials, DuBroff et al claimed that “the evidence presented challenges cardiovascular disease prevention through targeted reductions of LDL-cholesterol”. However, it should be noted that the concept authors claim to challenge has never been proved, nor properly tested (1). This raises the question of whether there is a need to disprove an unproven concept. In science, the burden is on the proof.
Nevertheless, if it was to disprove, we must recognize the limitations of the present study. Regarding testing "the target paradigm", the authors first categorized the trials as to whether they did or did not meet average LDL-cholesterol reduction recommended by AHA/ACC 2018 guidelines (2) for individuals. Then, they intended to test the association between reaching this arbitrary target (suggested by one specific guideline) with the trial being positive or negative regarding death or cardiovascular events. However, no statistical inference was performed for this main analysis and no significance level was presented for the interaction between reaching the target and having clinical benefit. Instead, in this systematic review that intended to test a hypothesis that implied interaction phenomenon, the authors "intentionally did not perform a meta-analysis" under the justification that trials “involved three different drug classes”.
Finally, as the authors noted, it was a systematic review of s...
Show MoreLike so many purported pundits, DuBroff R, de Lorgeril M [1] have attempted to dispute the significance of the role of saturated fat (triglycerides) and LDL-cholesterol in the development of coronary artery disease, while noting the importance of inflammation itself [1,2]. In law, ignorance of the law is not a defense - the same is true for medicine. Not understanding something does not make you an expert [2] and it does not make your argument valid. Appealing to the court of public opinion does not make it so either. Accordingly, we present a brief explanation of why the authors [1,2] – and others – have presented an invalid discussion of the role fat and LDL-cholesterol plays in coronary artery disease.
In the mid-1990s, as one of the reviewers for the American Heart Association, the first author of this letter, Dr Richard M Fleming (RMF) introduced a then controversial theory stating that Coronary Artery Disease (CAD) is the result of an inflammatory process, which builds up within the walls of the arteries impairing their ability to dilate and increase coronary blood flow when needed; thus producing regional blood flow differences resulting in angina [3-6] and ultimately myocardial infarction (MI) and death.
In recent years, people promoting various dietary and lifestyle practices – particularly those promoting LowCarb-Keto diets, have used the obesity epidemic to focus attention on obesity and weight loss. These same individuals have not demonstrated th...
Show MoreThank you for this measured summary of the recently published HYGIA trial. I am pleased to see you mention the BedMed study ongoing. Readers may be interested to know that there is another study, already in follow-up, which will provide further evidence on whether night-time dosing of blood pressure medications really is better in the prevention of cardiovascular events and mortality.
The University of Dundee's Treatment in Morning vs Evening (TIME, www.timestudy.co.uk) study, funded by the British Heart Foundation, aims to answer the same research question. TIME has recruited 21,104 participants across the UK and should finish in the first half of 2020.
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