Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Should women be offered statin treatment? Certainly not!
- Uffe Ravnskov (11 May 2007)
-
Why Statins Should Not Be Prescribed To Women
- Paul J. Rosch (12 May 2007)
-
A sexy debate?
- George Loucas Tzanis, Philadelphia, USA 19107 (13 May 2007)
-
Absence of Evidence or Evidence of Absence?
- Peter R Bates (14 May 2007)
-
Why categorically deny treatment?
- Phillipa J Rispin (15 May 2007)
-
Why would anyone want low serum cholesterol?
- Barry A Groves (15 May 2007)
-
Thrombus: cause or consequence of myocardial infarction?
- Carlos Monteiro (15 May 2007)
-
Living off the fat of the land
- Peter J Selley (17 May 2007)
-
Re: Living off the fat of the land
- Peter W Ward (17 May 2007)
-
Re: Thrombus: cause or consequence of myocardial infarction?
- Alejandro F. Luque-Coqui (18 May 2007)
-
Lets be FAIR to the FAIRER sex
- Carolyn M Balaam (18 May 2007)
-
Low dose Statins are effective in Post menopausal women for primary prevention of Coronary Heart Disease (CHD)
- Professor Pranab Kumar Bhattacharya, Bhattacharya Rupak Bsc(cal),Msc(JU), Islam Sahidul DM(cal)Cardio RMO ICVS, IPGMER, Chatterjee Bhabani Prasad DM(Cal) Cardio consultant Cardiologist Practioners (19 May 2007)
-
Re: Re: Thrombus: cause or consequence of myocardial infarction?
- Carlos Monteiro (19 May 2007)
-
Would you bet?
- Luca Mascitelli (20 May 2007)
|
|
|||
|
Uffe Ravnskov, independent researcher Magle Stora Kyrkogata 9, 22350 Lund, Sweden
Send response to journal:
|
Professor
Grundy´s main argument for prescribing cholesterol lowering drugs to women is
that such treatment reduces their risk of cardiovascular events.1
Obviously he is dismissing the fact that no trial or meta-analysis has found any
effect on coronary or total mortality in women. Or perhaps he feels that the
relatively ‘tiny’ reduction in non-fatal cardiovascular events overwhelms
the adverse effects. It is true that, according to all industrial-sponsored
trial reports, side effects from statin treatment are rare, but much evidence
tells us that they are underreported.2 Muscular symptoms, for
instance, are said to occur in less than one percent, but researchers
independent on the drug companies have found the frequency to be 10-20 %,3
64 %4 and even 80 %.5 This side effect may not only be
painful, it also hampers exercising, the most important preventive measure for
cardiovascular disease.
Competing interests: None declared |
|||
|
|
|||
|
Paul J. Rosch, Physician 124 Park AVe., Yonkers, NY 10703 USA
Send response to journal:
|
Grundy's conclusions are based on Framingham data describing cholesterol as a "risk factor" for coronary heart disease, which implies that it is a causative agency. However, like hundreds of others so-called "risk factors", elevated cholesterol is actually a "risk marker", that merely shows some statistical association with various coronary events. A deep earlobe crease and premature baldness are also in this category but correcting them with plastic surgery or a hair transplant does not prevent coronary disease and neither does lowering cholesterol. In point of fact, follow-up Framingham data revealed a direct association between falling cholesterol levels over the first 14 years of the study and increased mortality rates over the following 18 years. For men above the age of 47, those with low cholesterol had mortality rates greater than those with high cholesterol. Those whose cholesterol had decreased spontaneously over 30 years were at greater risk of dying from heart disease than those whose cholesterol had increased. "For each 1% mg. drop in cholesterol there was an 11% increase in coronary and total mortality." In addition, the majority of patients with heart attacks do not have elevated cholesterols. The MRFIT (Multiple Risk Factor Intervention Trial), which was the largest and most serious effort to prove the links between the original Framingham heart disease risk factors of cholesterol, cigarette smoking and hypertension, showed no significant difference in coronary disease between the intervention group where these presumed etiologic factors were reduced, compared to controls. After ten years of adhering to a diet in which cholesterol consumption was cut by 42 percent, saturated fat consumption by 28 percent and total calories by 21 percent, there was a slight lowering of coronary heart disease mortality rates. However, this benefit was far outweighed by significantly increased total death rates from hemorrhagic stroke, cancer, suicide, accidents and violence. Kendrick correctly raises the issue of costs, which is a far greater problem in the U.S., due to the hundreds of millions of dollars spent on direct to consumer TV and other media advertising. This may be a factor in the exorbitant costs of statins, which are over 4,000 percent for Zocor (simvastatin) and over 4,700 percent for Lipitor (atorvastin) more than the cost of raw materials. With the possible exception of New Zealand, where it may soon be banned, the United States is the only country that permits direct to consumer advertising, which encourages the use of drugs for individuals in whom no benefits have been shown. As a result, there are currently several suits against Pfizer for false Lipitor advertising to women and anyone over 65. As Grundy indicates, the Framingham data show that "only a few women without cardiovascular disease have a 10 year risk of coronary heart disease over 10% and the vast majority of these are over 60. He also argues that estimating absolute risk before starting statin therapy will insure that statins will not be prescribed inappropriately. However, the claim that "For every 1% fall in cholesterol there will be a 2% reduction in risk for coronary heart disease" refers to relative risk, which is deceptive and quite different. A study may show that after five years on a statin, patients had 34% fewer heart attacks than controls on statins, so that there is 34% relative risk reduction. What you are not told is that the absolute risk reduction is only 1.4% and that if the drug is taken by seventy-one people every day for five years, it will prevent one person from having a heart attack - but it is not known if that person will be you. Indeed, you will never see an advertisement that stating that a statin reduces heart attacks, if you look at the fine print on the bottom in mice type, which is mandated in some instances, it will say: Lipitor has NOT been shown to prevent heart disease or heart attacks.” ”Crestor has NOT been shown to prevent heart disease or heart attacks" Finally, any alleged cardioprotective effects of statins are clearly not related to lowering cholesterol or LDL since they are seen when these values are normal or low and a clear dose response relationship has never been demonstrated. Benefits are more likely due to anti-inflammatory, antithrombotic or other "pleiotropic" effects that do not correlate with lipid levels. Therefore, current criteria for dosage and duration of statin therapy based on achieving an arbitrary LDL level that few can achieve will only guarantee higher statin doses for longer periods of time that are known to increase the incidence of adverse side effects. This may account for the well-known poor adherence to statin therapy. Physicians and the public have a right to know about views contrary to the current cholesterol-coronary disease hypothesis but it is difficult to disseminate this information because of the powerful cholesterol cartel of manufacturers of cholesterol lowering products, low fat foods and blood testing equipment. Medical publications and the media do not want to risk losing their lucrative advertising revenues and those who oppose this dogma suffer severe retaliation and ad hominem attacks. Kilmer McCully lost his laboratory support and could not find employment for two years for suggesting that homocysteine might be as important a cause of coronary disease as cholesterol. Uffe Ravnskov's book, The Cholesterol Myths, was burned on a Finnish TV program and he was unjustly defamed on a Dutch TV program that aired his views. The British Medical Journal should be highly commended for sponsoring this open debate based on scientific data. Competing interests: None declared |
|||
|
|
|||
|
George Loucas Tzanis, Physician Jefferson Medical College, Philadelphia, USA 19107
Send response to journal:
|
Many women (and men) with isolated elevations in LDL cholesterol will live happy lives unburdened by cardiovascular disease. Others will have coronary events at a premature age with the same underlying pathophysiology as those men who benefit from statins. I think the debate should not be about whether women as a sex should be offered treatment or not. Rather the debate should be about how we should educate women (and men) about their personalized risks and benefits from various therapies that are available. Now that would be sexy. Competing interests: common sense |
|||
|
|
|||
|
Peter R Bates, Consultant in Metabolic Medicine Dept Metabolic Medicine, 23, Kensington Place, St Helier, Jersey, Channel Islands UK JE2 3PA
Send response to journal:
|
Since my time at medical school I have watched with interest an increasingly beleaguered and strident group of voices fight a rearguard action against the 'cholesterol hypothesis' of atheromatous disease. I am long enough in the tooth to recall standard pathology texts of the 1980s giving prominent space to the view that myocardial infarction had little if anything to do with coronary thrombosis.(1) Doubtless some believe that still, although their voice has been lost to mainstream discourse since the landmark trials of thrombolytic therapy. The 'anti-cholesterol hypothesis’ faction however continue to retreat to ever higher yet more circumscribed ground on which to make their stand, in this case identifying a sub-group within which the effect of LDL reduction on that hardest of end-points (total mortality) is yet to be definitively proven in randomised controlled trials.(2) Increasingly, doing so in the name of evidence-based-medicine subverts the paradigm, which exhorts us to synthesise dispassionately the full and rich spectrum of evidence available then apply it as best we can (inevitably with some extrapolation) to the unique patient before us. To demand statistically significant hard outcome data applicable to every sub-group our patient may belong to before applying an intervention is evidence-based-medicine as clinical straitjacket. I fear Dr Kendrick would find himself therapeutically impotent in most patient encounters were he to apply this 'reductio ad absurdam' approach systematically. There comes a point in assessing the evidence for a treatment approach (in this case the use of statins to lower LDL cholesterol) when it has been shown to be so broadly effective in the generality that the null hypothesis to be disproved becomes the expectation that it will be equally effective in specific sub-groups in the absence of convincing evidence to the contrary. If one has dropped a large number of differently coloured rubber balls to the ground and found all of them to bounce it is reasonable to expect a similar result when handed another coloured ball made from similar material, until experiment demonstrates otherwise. It is in this sense that absence of incontrovertible evidence of effectiveness in women is not incontrovertible evidence of absence of effectiveness, a point well made by Professor Grundy.(3) The results from the statin trials do not point to highly divergent end points for men and women. The point estimates of effect are fully consistent with the null hypothesis of these studies that women benefit from statin therapy to the same degree as men bearing similar levels of cardiovascular risk. Indeed, some large and well-known studies in primary (AfCAPS/TexCAPS(4)) and secondary (CARE(5), 4S(6)) prevention showed more efficacious point estimates of relative risk reduction for women than men. With respect to the case in point, I submit that it is for Dr Kendrick to prove by reference to sufficiently-powered randomised controlled studies or meta-analyses that effects on total mortality (or indeed lesser cardiovascular endpoints) in women treated with statins differ statistically and systematically from those seen in men. This is not possible, since such studies do not exist. By this reasoning, it is Dr Kendrick who to date has not been able to assemble a fully credible evidence base for his thesis. Trawling secondary analyses of major trials to highlight non-significant apparent variations between sub-groups in the major treatment effect is a valid method to generate hypotheses for definitive future study but in the meantime deriving treatment decisions from such an exercise as Dr Kendrick does is scientifically invalid and 'Bad Medicine'. Of course, Dr Kendrick's central thesis, expounded repeatedly and at length elsewhere, is not merely that statins are ineffective in women but that atherosclerotic disease has little or nothing to do with LDL cholesterol levels in either sex.(7) Dr Kendrick and his ilk do us a great service by continually challenging our assumptions and forcing us to return to the literature to test what we thought we knew. The debate generated is enjoyable to watch and to participate in, but meantime what is the pragmatic physician to do given our present state of knowledge, confronted by a diabetic Maori woman aged 70 at apparently high risk of future vascular events? Although there should always be room in science and medicine for elegant counter- hypotheses such as Dr Kendrick’s, presently the overwhelming message of the epidemiological and experimental literature regarding cholesterol and vascular disease remains that statins do ‘exactly what it says on the tin’. They lower LDL cholesterol levels and by that action reduce cardiovascular morbidity and mortality without any clear evidence for heterogeneity of effect between sub-groups at similar baseline risk.(8,9) Until the synthesised evidence proves otherwise, extrapolate and treat. References: 1. Muir’s Textbook of Pathology 12th Edition, Anderson JR (ed.) Edward Arnold, London 1985 2. Kendrick M. Should women be offered cholesterol lowering drugs to prevent cardiovascular disease- NO. BMJ 2007;334:983 3. Grundy SC. Should women be offered cholesterol lowering drugs to prevent cardiovascular disease- YES. BMJ 2007;334:982 4. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of Air Force/Texas coronary atherosclerosis prevention study. JAMA 1998;279:1615-22. 5. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335: 1001-9. 6. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S). Lancet 1994;344:1383-9. 7. The Great Cholesterol Con, Kendrick M. John Blake, London 2007. 8. Cholesterol Treatment Trialists’ Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366:1267-1278. 9. Law MR, Wald NJ, Rudnicka AR Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis BMJ 2003; 326: 1423-1427. Competing interests: PB has received assistance with the cost of attending conferences from a number of companies that market statins |
|||
|
|
|||
|
Phillipa J Rispin, Freelance medical writer-editor Montreal, Quebec, Canada H4A 2H5
Send response to journal:
|
Should women be offered statin treatment? Uffe Ravnskov replies “Certainly not!” and cites, among other reasons, the great risk of becoming infertile or of giving birth to a child with malformations. These do not seem to be good reasons for denying treatment –- any treatment -- to a competent and informed patient. Why not let the patient decide if the possibility of infertility will be a problem for her and then discuss the advisability of medication? Why not let her decide if she is willing to prevent or to terminate pregnancy and then discuss whether she should take or not take a certain medication? Among female candidates for statin treatment would not some be post-menopausal? In that case, the issue of fertility is entirely irrelevant. Denying a treatment to all because it might be harmful to some does not seem right. Competing interests: None declared |
|||
|
|
|||
|
Barry A Groves, Independent Researcher, maintains www.second-opinions.co.uk OX7 6LP
Send response to journal:
|
I know this debate applies only to women; however, with the evidence of the harm that low cholesterol does in both sexes, I would like to widen it slightly. Studies show that: Low cholesterol increases overall risk of death in young, middle aged and elderly men. Low cholesterol increases overall myocardial infarction in women. Low cholesterol increases cancer risk. Specific cancers are: Squamous cell cancers; Small cell lung cancers; Liver cancer; Multiple myeloma; Adrenal cancer; Colon cancer and oother gastrointestinal cancers; Brain cancers and eight Cancers of the blood. Low cholesterol compromises immune function. There are more Infections and deaths in surgical patients with low cholesterol levels. Low cholesterol has deleterious effects on the brain. Conditions associated with low cholesterol include: Depression; Mood changes; Aggressive behaviour; Abuse of children and partners; Suicide; Violent deaths; Alzheimer’s disease; Parkinson’s disease; Strokes and cerebral haemorrhage. Low cholesterol is more common in Diabetes and obesity. It also increases: Kidney disease; Crohn’s disease in children; and Sickle cell anaemia. On the other hand, high cholesterol protects against ischaemic heart disease risk and congestive heart failure. So, what do we mean by 'low'? The evidence suggests that a Low cholesterol level is one that is below about 4.8 mmol/L. In some of the cancer studies, a level below 7.0 mmol/L increases risk. The real question is: why on earth would anyone want to lower their cholesterol level? (63 references, which is why I haven't included them, but they are available on request barrygroves@tiscali.co.uk.) Competing interests: None declared |
|||
|
|
|||
|
Carlos Monteiro, President Infarct Combat Project
Send response to journal:
|
Yes, some still, as ourselves, believing that coronary thrombosis is a result not the cause of myocardial infarction. We agree with Dr. Peter R Bates when he says the voice of those who have the opinion that coronary thrombosis is a consequence of myocardial infarction has been lost to mainstream discourse in favour of thrombolytic therapy. However, the proof of efficacy of thrombolysis for AMI depends on 9 randomized placebo-controlled trials totalling 58,511 patients. The meta- analysis of these trials showed an overall survival advantage of about only 2% (11.5% vs 9.6 %) in favour of thrombolysis meaning that 2% of patients would be benefited by thrombolysis and 98% would not. It should take into account that the use of thrombolytics comes with an additional clinical price besides potentially fatal bleeding complications (1). Regarding the coronary thrombus as consequence of acute myocardial infarction, the great American pathologist Dr. William Roberts told in 1972 (2): "The infrequency of coronary thrombi in patients dying suddenly of cardiac disease and in those with transmural necrosis who never have shock or congestive heart failure suggests that the thrombi may be consequences rather than causes of AMI". In the same direction Giorgio Baroldi, another great pathologist and professor from Italy, reinforced this view in a paper from 2005 (3). He stated: a) infarct size is not related to severity of coronary atherosclerotic lumen reduction and number of main vessels with severe stenosis; b) long survival (interval from the beginning to death) prevails in large infarcts; c) extensive myocardial fibrosis, as expression of chronic disease, does not correlate with infarct size; and d) the frequency of an occlusive thrombus is significantly higher in the largest infarcts supporting its secondary formation. By the way, we defend the following coronary heart disease theories:
Carlos Monteiro
References: 1) Thrombolysis for Acute Myocardial Infarction: Drug Review, David K. Cundiff, Medscape General Medicine, January 2, 2002. Full free text at http://www.medscape.com/viewarticle/414942 2) Coronary Arteries in Fatal Acute Myocardial Infarction, ROBERTS, WC, Circulation, Vol XLV, January 1972 Full free text at http://circ.ahajournals.org/cgi/reprint/45/1/215 (Reprint with 13 MB) 3) Baroldi G, Bigi R, Cortigiani L: Ultrasound imaging versus morphopathology in cardiovascular diseases: coronary collateral and myocardial ischemia. Cardiovasc Ultrasound 2005, 3:6 Full (free) text at http://www.cardiovascularultrasound.com/content/3/1/6 Competing interests: None declared |
|||
|
|
|||
|
Peter J Selley, General Practitioner Bow Devon EX17 6EY
Send response to journal:
|
It is a sad state of affairs that the subject of a debate is already enshrined in the NICE-driven Quality and Outcomes Framework (QOF) - the annual reward and incentive programme detailing GP practice achievement results. http://www.ic.nhs.uk/services/qof I feel very uneasy about the use of more and more drugs to drive patients' blood pressures and cholesterols endlessly downwards, egged on by the financial carrot of QOF. One small consolation is that, after starting a life-long sentence of statins, patients do seem to die happier, if not any later, knowing that their cholesterol (checked annually of course) is lower. Well done Dr Kendrick Competing interests: Lowering women's cholesterol boosts my pay |
|||
|
|
|||
|
Peter W Ward, GP Central Gateshead Medical Group NE8 5LD
Send response to journal:
|
I have fantasized about being able to offer women who the QOF deems suitable for statins a choice between the tablet or money. The choice would be the statin or a monthly payment equivalent to the cost of the statin into their bank account. I wonder what would increase their health and sense of well being the most? Competing interests: None declared |
|||
|
|
|||
|
Alejandro F. Luque-Coqui, Independent cardiologist Celaya Gto Mexico
Send response to journal:
|
Well the same great American pathologist William Roberts also said " "Statins are miracle drugs, that are to atherosclerosis what penicillin was to infectious disease" (1) All this discussion about cholesterol and its role in atherosclerosis is especially based on beliefs and feelings. Whether thrombus is cause or consequence of myocardial infarction was an interesting issue until in a classic and multicitation study, DeWood(2) clarified in a very clever study this controversy, defining the prevalence of total coronary occlusion in the hours after transmural myocardial infarction, with coronary arteriography in 322 patients admitted within 24 hours of infarction. Total coronary occlusion was observed in 110 of 126 patients (87 per cent) who were evaluated within four hours of the onset of symptoms; this proportion decreased significantly, to 37 of 57 (65 per cent), when patients were studied 12 to 24 hours after the onset of symptoms. So at that time I said "now I understand why pathologists could not find intracoronary thrombus unless the autopsy could be done very early, and 27 years later I see this commentary, I respect that but... of course I strongly disagree. So my conclusion is that Shaughnessy and Slawson were absolutely right when they classified medical thoughts as: Levels of belief (3)
and everybody can believe..... whatever. 1.- Roberts WC. The underused miracle drugs: the statins drugs are to atherosclerosis what penicillin was to infectious disease. Am J Cardiol 1996;78:377-378 2.- DeWood MA, Spores J, Notske R et al. Prevalence of total coronary oclussion during the early hours of transmural myocardial infarction. N Engl J Med 1980;303:897-902 3.- Shaughnessy AF, Slawson DC. Easy ways to resist change in medicine BMJ 2004; 329: 1473-1474. Competing interests: None declared |
|||
|
|
|||
|
Carolyn M Balaam, Practice Nurse Pound House Surgery HP10 0EE
Send response to journal:
|
SD seeking clarification of PPI, 18.5.07 Scenario: Mother dies at 57 from IHD - smoker all her life. Daughter, non-smoker (unless you count passive for 18 years), healthy lifestyle, health conscious nurse with cholesterol of 6.8 goes to GP. Persuades GP to commence on statin "to see if it makes a difference". Probably 20% he says. Blood test 1 month later - cholesterol 4.3! Yes,I want to see my first new Grandchild grow up. I'll keep taking the pills whatever the debate and arguments because I don't want to have an MI at 57! I've seen an awful lot of men who come to their GP abusing their bodies with a high alcohol intake, eating spicy curries, and smoking who are given a proton pump inhibitor and they have NO intention of changing their lifestyles. Do we decide NOT to treat them with (high cost) PPI's because they won't adhere to health advice? Maybe that should be another topic! Competing interests: To see my Grandchildren grow up! |
|||
|
|
|||
|
Professor Pranab Kumar Bhattacharya, Professor of Pathology, Incharge Unit, Blood Bank& VCTC, Cytogenetics,Ronald Ross Malaria Clinic Institute of POst Graduate Medical Education & Research, 244A AJC Bose Road, Kolkata-700020, W.B,, Bhattacharya Rupak Bsc(cal),Msc(JU), Islam Sahidul DM(cal)Cardio RMO ICVS, IPGMER, Chatterjee Bhabani Prasad DM(Cal) Cardio consultant Cardiologist Practioners
Send response to journal:
|
Statins can reduce the risk of cardiovascular events and are cost effective. Use of Statins has become mandatory in range of disorders from coronary heart disease to ischemic cerebro-vascular diseases and in several others high risk conditions such as in diabetes mellitus and in hypertension. Statins showed effective out come even for severe infections such as in pneumonias, sepsis and in bacterimia. At least six(6) studies have proved statins use with decreased risks of severe sepsis or death(1). Coronary heart disease (CHD) remains a major wide world threat in relation to human mortality and morbidity in the developed and in the developing countries. The disease is initiated with the assault of multiple risk factors on endothelium and progress to formation of sub optimal foam cells, atheroma and diffuse coronary artery disease. The coronary arteries are eventually riddled with diffuse atheroma at different stages of evolution & progression, including angiographic stenosis, typical of stable angina with other vessels evolution like carotid artery, resulting stroke For primary prevention of CHD in general population and in community begins with the risk factor control. Seven major conventional risk factors in the Framingham studies were age, sex, BP, Total and LDL cholesterol, Smoking, Diabetes Mellitus and LVH.. For patients with stable angina only hypertension therapy and lipid lowering drugs with statins receive level A recommendation from US authorities and Europeans authorities that focuses on life style control, aspirin and Statins(2). The use of diet rich in fruits, vegetables, whole grains, fish ,low salt, soya, nuts ,low fat dairy products, omega-3- fatty acids containing fish- causes reduction of BP, weight and attenuation of inflammation and coagulation process. Therefore these diets can be expected to reduce the rate of progression of coronary artery disease. Increasing evidences show protective effect of Omege-3 fatty acids derived from oily fish or from plant extract. Moderate alcohol intake gives mortality reduction rate20%. Aerobic isometric exercise at least 3times a week for at least 20 minutes at 70-85% of heart rate can reduce mortality form CHD 20%. Results of observational; studies in different populations indicate a continuous positive relation ship between CHD risk and blood cholesterol concentration (specially LDL level) that extends well bellow the range seen in many developed countries population without any defective threshold bellow which a lower cholesterol concentration is not associated with a risk. The basic aim henceforth is to reduce the level of LDL 1.0- 1.5 mmol/L over 5 years period. In the context of lipid and cardiovascular risk is principally determined by concentration. of LDL cholesterol and HDL cholesterol ratio and to a lesser extent on triglyceride conc. Cholesterol to HDL cholesterol ratio is thus an appropriate measure to risk assessment and should be preferred target for treatment. Reduction in coronary death and non fatal AMI become 11% in the 1st year, 24% in the 2nd year, 33% in 3rd -5th year and 36% in 6th & subsequent years in a Scandinavian study (3). The most compelling evidences for cholesterol lowering comes from the trials using statins with non-fatal & fatal clinical cardiac events and end points like AMI or cardiac death. The early major statins trials in people with established CVD was using Simvastatin and Paravastatin and the trials were CARE, LIPD and in asymptomatic individuals who were at risk of developing CVD were using Paravastatin and Lovastatin were VOSCOPS, AFCAPS, TEXCAPS. All these trials showed significant reduction in coronary events and mortality both in men & in women by 23%. Over the past 10 years fourteen (14) randomized controlled trials were established with effects of statins across a broad range of patients group (5). CTT collaborators study considered 90,056 people of age range 35-75 years where 24% participants (21,575) were women, having all 21% diabetes mellitus and 47% preexisting CHD and 55% had history of hypertension. Their Pre- treatment levels of LDL cholesterol were 3.79 mmol/L ranging from 3.03 to 4.96mmol/L. After statin therapy 23% reduction happened in all case mortality. Only 8116 cases had death of which 57% were from vascular and 43% from non-vascular causes. The study CTT concluded that incidence of major coronary events, coronary revascularization & stroke reduces proportionally to reduction of LDL per mmol/L(5). Another significant meta analysis of CARE, LIPID, VOSCOPS, AFCAPS/ TEXAPS trial showed significant reductions in major coronary events by 31%, coronary mortality by 29% and all cause mortality reduced by 21% But in most of the statin trials women were poorly represented and were considered to achieve a lower risk reduction then men, frequently not reaching the statistical significance Costa. J et al in a meta analysis of a randomized controlled trials where they included 12 studies both diabetic and non diabetic men & women showed that use of statin for reduction of LDL cholesterol, caused reduction for major coronary events 21% in diabetic patients and 23% in non diabetic patients (both men & women)(4). The another study by Haruo Nakamura and his colleagues in a randomized open labeled study investigating Paravstatin low doses (10-20 mg/day) with 8000 population of which 69% were women (2718) kept with diet group and 68% women (2387) were kept with Diet+ Paravastatin, having BP 132+-16.8/78.4+-10.4. In the paravastatin group, 42% had hypertension, 21%, had DM and 6% were smoker & total cholesterol 6.27mmol/L, TG 1.44mmol/L, HDL 1.49 mmol/L, LDL 4.05 mmol/L. Their study showed 30% reduction of end point of coronary heart disease in the diet + paravastatin group versus the diet group for the AMI( fatal or non fatal) or SCD or angina or coronary revascularization(6) So use of statins has a definite role in primary prevention of coronary heart disease in both men & women. The JBS-2 guide line is to provide low doses of statin(10mg/daily) to individuals who are >20% CVD risk. In the West Bengal we the cardiologists often get AMI or acute coronary syndrome even a large group of patients in the middle aged around 50 years who have average cholesterol level< 200mg/dl, average LDL around 100mg/dl and average HDL 30 mg /dl without any risk factors. The present authors of this article also thinks it is better to provide statin to all men aged >40years and over even without CVD risk and in women at post menopausal women with one or more risk factors like hypertension.,obesity, family history of premature death by CHD, or of Indian origin, or with diabetes mellitus. Use of Statin in low dose also beneficial& also cost effective at menopausal period & on ward References 1)Reimar.W.Thomson “ The lesser kown effects of Statins, bnefits on infections Out comes may be explained by healthy user effect “ BMJ 333:11th nov 980- 81:2006 2)Lionel.H. Opie; Patrick. J. Comnerford, Bernard J Gersh “ Controversies in Cardiology-1 Series” The Lancet 367: Jan7:69-78 3)The Scandinavian Simvastatin Survival Study Group: Randomized trial of cholesterol lowering in 4444 people with coronary heart disease: The Scandinavian Survival Study “ The Lancet 344:1389-99:1994 4)Joao. Costa, Merganda Borges, Daudio David Et al “ Efficacy of lipid lowering drug treatment for diabetic and non diabetic patients : Meta- analysis of Randomized controlled trial” BMJ 332:13th may :1115-18:2006 5)Cholesterol Treatment Trialists (CCT) Collaborators “ Efficacy and safety of cholesterol lowering treatment: Prospective meta analysis of data from 90056 participants in 14 randomized trials of Statin “ The Lancet 366:1267_78:2006 6)Haruo Nakamura. Kikuo Arakawa, Hiroshiqe “ Primary prevention of Cardiovascular disease with Paravastatin in Japan (The MEGA Study): a prospective randomized controlled trial “ The lancet 368:1155-63:2006 Acknowledgement= Authors gratefully acknowledges contribution of Mr Ritwik Bhattacharya & Bholanath Bhattacharya of Sodepur 24 parganas (north)Kol-110 Miss Upasana Bhattacharya of Delhi Public School Ruby park Kolkata in this article Authors_ *Professor Pranab Kumar Bhattacharya MD(cal), FIC path(Ind) Professor of Pathology, In charge of Unit, In charge of Blood Bank &VCTC,In charge of Cytogenetics, Ex- In charge of Ronald Ross Malaria Clinic Institute of Post Graduate Medical Education &Research (IPGMER)244A AJC Bose Road , Kolkata-700020, India 2) **Mr. Rupak Bhattacharya Bsc(cal), Msc( JU) Purbapalli Po= Sodepur, 24Parganas(north), West Bengal, Pin 700110 3) *Dr. Sahidul Islam MD (cal)Dip Card(Cal), DM (cal) RMO Cum Clinical Tutor Institute of Cardiovascular Sciences IPGMER, Kolkata-20 4) ***Dr. Bhabani Prasad chatterjee DM(cal) Cardio Consultant Cardiologist practioners Competing interests: None declared |
|||
|
|
|||
|
Carlos Monteiro, President Infarct Combat Project
Send response to journal:
|
Unfortunatelly, another ‘pearl’ from William Roberts it was said in 1984: “When I have an acute myocardial infarction take me to the hospital that has a cardiac catheterization laboratory and open cardiac surgical facilities” (1) Regarding De Wood I should cite again Giorgio Baroldi and Colleagues (2): "The very high frequency of coronary occlusion seen angiographically in AMI patients does not correspond to that observed in pathological studies in which the mean figure is 50% for AMI and 29% for SUD patients. Nevertheless, different selection of material, divergent definition and an absence of a correct correlation of all pertinent variables give reason of dissimilar conclusions. In 200 selected AMIs and 208 SUD cases the unique cause of occlusion was a thrombus found in 41% and 29% respectively. In AMI group it correlated significantly with a lumen reduction greater than 70% (93%), length of plaque more than 6 millimeters (95%), its concentric shape (100%), prevailing atheroma (84%), medial neuritis (92%) infarct size greater than 50% (86%). SUD cases showed a similar behavior. In reality, both clinicians and pathologists observe a phenomenon which started before, missing its onset and sequence of events to distinguish whether primary or secondary." In an editorial by O’Neill, W.W. in 1998 (3) published in American Journal of Cardiology he has commented about the results of study showing the absence of thrombosis during the AMI in substantial number of patients. This study made by Murakami et al from Japan (4), using intracoronary catheters to aspirate occlusive tissues, has been performed during myocardial infarction and confirm the pathological findings that intracoronary thrombus is absent in a substantial number of patients indicating it contributes little to the pathogenesis of average AMI. Also, Rittersma et al in a recent study examined (5, 6) retrieved thrombus material aspirated using the Rescue percutaneous thrombectomy catheter (Boston Scientific, Natick MA) in 211 patients undergoing primary PCI within six hours of symptom onset. They then established, by histological indicators, the age of the aspirated thrombi. The researchers found thrombus in 199/211 patients, of whom fresh thrombus was identified in just under half. By contrast, 51% of patient samples contained thrombus that had lytic or organized changes suggesting that it had originated days or weeks before the occlusive event. Strikingly, clinical characteristics did not differ between the patients with fresh thrombus and those with "older" thrombus, although men were more likely to have fresh thrombus than were women. (6). By the way, "red" thrombus, namely a coagulum, is frequently and erroneously considered as thrombus. Pathological findings in necropsy showing coronary thrombosis as consequence of AMI and not its cause were reported by different groups since almost 50 years ago (7, 8, 9). These were confirmed by other experimental studies using different procedures (10, 11). Finally I have to mention the recent review from Giorgi Baroldi and colleagues (12), where they have discussed the behaviour and meaning of components of the human coronary atherosclerotic plaque to emphasize the inconsistency of current myths like: 1. Experimental hypercholesterol model and correspondent human conditions do not represent the natural history of atherosclerosis in coronary arteries in the general population. 2. Physiological intimal thickening can not be interpreted as starting point of the atherosclerotic process. 3. Fatty streak does not represent the early atherosclerotic lesion. 4. Calcification is not synonymous of severe stenosis. 5. Hemorrhage is not consequent to endothelial fissuration. 6. Prevention of macrophage "inflammation" as source of substances able to disrupt the fibrous cap allowing rupture and thrombosis as well as identification of the thickness of fibrous cap to diagnose a vulnerable plaque may have little, if any, sense. Rupture and thrombosis may be secondary phenomena and not the cause of an acute coronary syndrome. 7. Degree and number of severe coronary plaques do not predict onset, course, complications and death in CHD. References: 1) When I have an acute myocardial infarction take me to the hospital that has a cardiac catheterization laboratory and open cardiac surgical facilities. Am J Cardiol. 1984;53(9):1410. Facts and ideas from anywhere William C. Roberts, MD http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=132529 2) Ultrasound imaging versus morphopathology in cardiovascular diseases. Coronary collateral circulation and atherosclerotic plaque Giorgio Baroldi, Riccardo Bigi and Lauro Cortigiani Full free text at http://www.cardiovascularultrasound.com/content/3/1/6 3) Coronary thrombosis during acute myocardial infarction: Roberts was right!, Am J Cardiology 1998 Oct 1; 82(7): 896-7) 4)) Intracoronary aspiration thrombectomy for acute myocardial infarction, Am. J Cardiology Oct 1;82(7):839-44) 5) Plaque instability occurs days to weeks before occlusive coronary thrombosis, Heartwire February 24, 2005 Shelley Wood at http://www.theheart.org/article/395155.do 6) Rittersma SZH, van der Wal AC, Koch KT, et al. Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis. A pathological thrombectomy study in primary percutaneous coronary intervention. Circulation 2005; 111:1160-1165. Full free text at http://circ.ahajournals.org/cgi/content/full/111/9/1160 7) Spain D.M. and Bradess, V.A.: The Relationship of coronary thrombosis to coronary atherosclerosis and ischemic heart disease (a necropsy study covering a period of 25 years) Am J Med Sci, 240:701, 1960 8) Frequency of coronary thrombosis related to duration of survival from onset of acute fatal episodes of myocardial ischemia, Circulation, 22:816, 1960; Roberts, W.C.: 9) Coronary arteries in fatal acute myocardial infarction, Circulation, 42:215, 1972, Roberts W. C.. 10) Hellstrom, H.R.: Myocardial infarct as a cause of coronary thrombosis, Circulation, 42 (Suppl III): 165, 1970 11) Erhardt, L.R. et al: Formation of coronary arterial thrombi in relation to onset of necrosis in acute myocardial infarction in man, a clinical and autoradiographic study, Am Heart J, 91:592, 1976) 12) Ultrasound imaging versus morphopathology in cardiovascular diseases. Coronary atherosclerotic plaque Giorgio Baroldi , Riccardo Bigi and Lauro Cortigiani Full free text at http://www.cardiovascularultrasound.com/content/2/1/29 Competing interests: None declared |
|||
|
|
|||
|
Luca Mascitelli, M.D. Chief of Sanitary Service Comando Brigata alpina Julia, Udine 33100 Italy
Send response to journal:
|
dear Professor Bhattacharya, put your statin in your drinking water: I won't drink it. I'm in my 40s, have a healty lifestyle, and my tot Chol is around 7. Your drug won't add one healthy day to my presumably long life (and I'm not a woman!!) Competing interests: Following Osler's statement: 'One of the first duties of the physician is to educate the masses not to take medicine.’ |
|||