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Urinary Tobacco Alkaloid Measurement in Patients Having Thromboangiitis Obliterans
LETTERS TO THE LETTERS TO EDITOR THE EDITOR Low-Dose Statin Concentration in Red Yeast Rice: A Confounding Effect on Outcome? To the Editor: The recent article by Becker et al1 reporting results from the Simvastatin vs Therapeutic Lifestyle Changes and Supplements: Randomized Primary Prevention Trial shows that patients with hyperlipidemia could benefit from lifestyle changes combined with ingestion of red yeast rice and fish oil. The significant weight difference between the 2 treatment groups—the patients in the alternative treatment group were obese and those in the simvastatin group were only overweight—is accounted for by the authors by an adjustment for baseline weight. However, even after this statistically correct adjustment, there is still the impression that the weight difference may have affected the results: the patients in the alternative treatment group lost about 5% of their body weight after a lifestyle change, with the expected changes in levels of triglycerides and high-density lipoprotein cholesterol. 2 Therefore, this part of the study confirms that reduction in body weight through dietary changes or increased physical activity optimally affects the lipid profile of obese patients and that excellent results are obtained when patients are made aware of the beneficial effects of such changes. The weight reduction in the alternative-treatment group cannot be the cause of the decrease in low-density lipoprotein cholesterol (LDL-C); indeed, even greater reductions in body weight have been shown not to affect LDL-C levels.3 Therefore, lifestyle changes and food supplements have had an important role in this decrease. The fact that red yeast rice contains low doses of lovastatin further obscures the comparison between the 2 groups. The authors have changed only the red yeast rice dose in accordance with the initial LDLC level; this implies that they are also aware of red yeast rice’s major cholesterol-lowering role. We would like to agree with the authors that dietary changes and increased physical activity lead to better LDL-C–lowering effects; however, in light of the results of the study, a more appropriate conclusion would be that the effect of low-dose statin therapy with food supplements and lifestyle changes is identical to the results achieved with therapeutic doses of statin. This finding is important because the lowering of the statin dose will lead to the reduction of adverse effects and will improve patient adherence to therapy. Plamen Hristov Yovchevski, MD, PhD Nadezhda Ivanova Doncheva, PhD Medical Institute of Ministry of Interior Sofia, Bulgaria 1. Becker DJ, Gordon RY, Morris PB, et al. Simvastatin vs therapeutic lifestyle changes and supplements: randomized primary prevention trial. Mayo Clin Proc. 2008;83(7):758-764. 2. Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association scientific statement on obesity and heart disease
© 2008 Mayo Foundation for Medical Education and Research
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from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006 Feb 14;113(6):898-918. Epub 2005 Dec 27. 3. Purnell JQ, Kahn SE, Albers JJ, Nevin DN, Brunzell JD, Schwartz RS. Effect of weight loss with reduction of intra-abdominal fat on lipid metabolism in older men. J Clin Endocrinol Metab. 2000;85(3):977-982.
In reply: The letter from Yovcheski and Doncheva highlights the importance of a careful diet and exercise program in reducing serum triglyceride levels and weight in people who are overweight. The Mediterranean diet has recently been found to lead to weight loss that was maintained for 2 years,1 suggesting that therapeutic lifestyle changes can be maintained for an extended period of time. In our study, the reduction of LDL-C in the alternative-treatment group was most likely due to the supplements provided to the participants and not simply to weight loss. This supposition was confirmed when we adjusted all variables for weight loss, including LDL-C levels; these results were not included in the article because of limits secondary to our small sample size. Although we agree with Yovcheski and Doncheva that therapeutic lifestyle changes can have a positive effect on the lipid profile of patients, we disagree with their conclusion that the “effect of low-dose statin therapy with food supplements and lifestyle changes is identical to the results achieved with therapeutic doses of statin.” The lovastatin equivalent of the dose used in our trial was 10 to 15 mg/d, a dose that would correspond to a simvastatin dose of 5.0 to 7.5 mg/d, far less than the 40 mg used in the standard group. We think that other properties of red yeast rice, specifically other monacolins, contributed to the 42% decrease in LDL-C seen in the alternative-treatment group. This intriguing and not well-studied effect of red yeast rice needs to be further investigated in larger trials with mortality and morbidity end points. Ingestion of fish oil may also have had a minor role in reducing LDL-C levels.2 David Becker Chestnut Hill Hospital Philadelphia, PA 1. Shai I, Schwarzfuchs D, Henkin Y, et al; Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359(3):229-241. 2. Lee JH, O’Keefe JH, Lavie CJ, Marchioli R, Harris WS. Omega-3 fatty acids for cardioprotection. Mayo Clin Proc. 2008;83(3):324-332.
Urinary Tobacco Alkaloid Measurement in Patients Having Thromboangiitis Obliterans To the Editor: The recent Residents’ Clinic by Geske et al1 points out the difficulties of diagnosing thromboangiitis obliterans (TAO or Buerger disease) when the patient admits past smoking but denies current tobacco use.1 Denial and rationalization are common features of tobacco dependence, and an objective measure of tobacco use is critical in such circumstances. The tobacco alkaloids nicotine and cotinine can be
October 2008;83(10):1187-1189
•
www.mayoclinicproceedings.com
1187
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
LETTERS TO THE EDITOR
measured in blood and urine and are biomarkers of nicotine exposure. Serum cotinine, with an elimination half-life of 18 to 20 hours, is able to detect nicotine use after 2 to 3 days of abstinence. However, elevated levels of both nicotine and cotinine are also common after use of therapeutic nicotine replacement products and so are not specific markers of tobacco use. In contrast, the urinary tobacco alkaloids anabasine and nornicotine are specific for tobacco use and can be used to distinguish patients who are abstaining from tobacco and using nicotine replacement therapy from those who are smoking.2 Because anabasine and nornicotine are not metabolites of nicotine, they indicate current tobacco use if detected in urine. As mentioned by Geske et al,1 the relationship of tobacco to TAO has been known for decades. In an early series from Mayo Clinic, only 5 of 350 men (aged 25-55 years) with TAO were nonsmokers.3 In the discussion, Dr W. J. Mayo quipped: “On the whole, smoking seems a habit which has possibilities for harm, and has little to its credit.” Of course, this report from Mayo Clinic dates to 1931, long before most of the detrimental effects of tobacco use were known. However, as Geske et al1 point out, the misconception that tobacco dependence treatment is unsuccessful in patients with TAO is common. Quite the contrary, we found that smokers with TAO were no more tobacco dependent than smokers with coronary artery disease; thus, treatment should be aggressively pursued in these patients.4 We also observed that patients with TAO smoked fewer cigarettes per day than patients with coronary artery disease and were more likely to have made a serious attempt to stop in the past. Certainly for smokers with such a severe medical problem as TAO, residential treatment for tobacco dependence offers the best option to stop and remain abstinent from smoking.5 An overall 1-year smoking abstinence rate of 45% was reported after an 8-day residential treatment program.6 In patients who continue to smoke, TAO is relentlessly progressive and results in chronic and severe pain, gangrene, and autoamputation. Urinary tobacco alkaloids should be measured in patients with TAO who deny smoking to detect surreptitious smoking. Aggressive tobacco dependence treatment, including residential treatment, should be offered to patients with this disease as soon as possible. Richard D. Hurt, MD J. Taylor Hays, MD Mayo Clinic Rochester, MN 1. Geske JB, Calvin AD, McDonald FS. 37-year-old man with painful foot. Mayo Clin Proc. 2008;83(7):821-824. 2. Moyer TP, Charlson JR, Enger RJ, et al. Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Clin Chem. 2002; 48(9):1460-1471. 3. Barker N. The tobacco factor in thrombo-angiitis obliterans. Proc Staff Meet Mayo Clin. 1931;6(2):65-68. 4. Cooper LT, Henderson SS, Ballman KV, et al. A prospective, case-control study of tobacco dependence in thromboangiitis obliterans (Buerger’s disease). Angiology. 2006;57(1):73-78.
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5. Hooten WM, Bruns HK, Hays JT. Inpatient treatment of severe nicotine dependence in a patient with thromboangiitis obliterans (Buerger’s disease). Mayo Clin Proc. 1998;73(6):529-532. 6. Hays JT, Wolter TD, Eberman KM, Croghan IT, Offord KP, Hurt RD. Residential (inpatient) treatment compared with outpatient treatment for nicotine dependence. Mayo Clin Proc. 2001;76(2):124-133.
In reply: We appreciate the insightful points made by Hurt and Hays. We agree that diagnostic studies of tobacco use would augment the evaluation of TAO and could prove particularly helpful in cases such as the one we presented, in which tobacco use was initially denied. In our case, angiography was required for the diagnosis of TAO; when the patient was presented with the angiographic findings while his mother was absent, he admitted to ongoing tobacco use. Urinary tobacco alkaloids might well be of benefit for assessing smoking cessation at subsequent follow-up visits for this patient. Given the strong linkage between tobacco use and TAO, we continue to advocate smoking cessation. Hurt and Hays provide excellent examples of data that further support this approach. Jeffrey B. Geske, MD Andrew D. Calvin, MD, MPH Furman S. McDonald, MD, MPH Mayo Clinic Rochester, MN
Hysteroscopic Sterilization in Women With Pulmonary Vascular Disease To the Editor: We read with interest the recent article by Famuyide et al1 on hysteroscopic sterilization in women with severe cardiac disease. We were particularly interested in the inclusion of patients with pulmonary vascular disease, whom the authors rightly describe as having increased risk of poor outcomes related to general anesthesia.2 The cohort described in this study included primarily patients with structural heart disease or acquired cardiac disease and associated pulmonary hypertension. Patients with pulmonary arterial hypertension (PAH) associated with congenital left-to-right shunt have a better prognosis than those with idiopathic PAH or PAH with other associated conditions.3 We have found hysteroscopic sterilization to be successful in patients with idiopathic PAH as well as congenital heart disease–associated PAH. Our clinic is a referral center for pulmonary vascular disease. Similar to the cohort described by Famuyide et al,1 our patients are counseled against pregnancy because of poor maternal and fetal outcomes with PAH.4 Many of our patients are treated with endothelin receptor antagonists, which are potentially teratogenic; thus, these patients require either sterilization or 2 reliable methods of birth control. We have referred 6 patients with PAH for hysteroscopic sterilization; 2 patients were unable to undergo the procedure, one because tubal ostia were not visible and one because of a previous tubal pregnancy, a contraindication to the procedure. In the remaining 4 patients (Table), all of whom successfully underwent hysteroscopic sterilization, no procedure- or anesthesia-re-
October 2008;83:(10):1187-1189
•
www.mayoclinicproceedings.com
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
© 2008 Mayo Foundation for Medical Education and Research
Mayo Clin Proc.
•
from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006 Feb 14;113(6):898-918. Epub 2005 Dec 27. 3. Purnell JQ, Kahn SE, Albers JJ, Nevin DN, Brunzell JD, Schwartz RS. Effect of weight loss with reduction of intra-abdominal fat on lipid metabolism in older men. J Clin Endocrinol Metab. 2000;85(3):977-982.
In reply: The letter from Yovcheski and Doncheva highlights the importance of a careful diet and exercise program in reducing serum triglyceride levels and weight in people who are overweight. The Mediterranean diet has recently been found to lead to weight loss that was maintained for 2 years,1 suggesting that therapeutic lifestyle changes can be maintained for an extended period of time. In our study, the reduction of LDL-C in the alternative-treatment group was most likely due to the supplements provided to the participants and not simply to weight loss. This supposition was confirmed when we adjusted all variables for weight loss, including LDL-C levels; these results were not included in the article because of limits secondary to our small sample size. Although we agree with Yovcheski and Doncheva that therapeutic lifestyle changes can have a positive effect on the lipid profile of patients, we disagree with their conclusion that the “effect of low-dose statin therapy with food supplements and lifestyle changes is identical to the results achieved with therapeutic doses of statin.” The lovastatin equivalent of the dose used in our trial was 10 to 15 mg/d, a dose that would correspond to a simvastatin dose of 5.0 to 7.5 mg/d, far less than the 40 mg used in the standard group. We think that other properties of red yeast rice, specifically other monacolins, contributed to the 42% decrease in LDL-C seen in the alternative-treatment group. This intriguing and not well-studied effect of red yeast rice needs to be further investigated in larger trials with mortality and morbidity end points. Ingestion of fish oil may also have had a minor role in reducing LDL-C levels.2 David Becker Chestnut Hill Hospital Philadelphia, PA 1. Shai I, Schwarzfuchs D, Henkin Y, et al; Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359(3):229-241. 2. Lee JH, O’Keefe JH, Lavie CJ, Marchioli R, Harris WS. Omega-3 fatty acids for cardioprotection. Mayo Clin Proc. 2008;83(3):324-332.
Urinary Tobacco Alkaloid Measurement in Patients Having Thromboangiitis Obliterans To the Editor: The recent Residents’ Clinic by Geske et al1 points out the difficulties of diagnosing thromboangiitis obliterans (TAO or Buerger disease) when the patient admits past smoking but denies current tobacco use.1 Denial and rationalization are common features of tobacco dependence, and an objective measure of tobacco use is critical in such circumstances. The tobacco alkaloids nicotine and cotinine can be
October 2008;83(10):1187-1189
•
www.mayoclinicproceedings.com
1187
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
LETTERS TO THE EDITOR
measured in blood and urine and are biomarkers of nicotine exposure. Serum cotinine, with an elimination half-life of 18 to 20 hours, is able to detect nicotine use after 2 to 3 days of abstinence. However, elevated levels of both nicotine and cotinine are also common after use of therapeutic nicotine replacement products and so are not specific markers of tobacco use. In contrast, the urinary tobacco alkaloids anabasine and nornicotine are specific for tobacco use and can be used to distinguish patients who are abstaining from tobacco and using nicotine replacement therapy from those who are smoking.2 Because anabasine and nornicotine are not metabolites of nicotine, they indicate current tobacco use if detected in urine. As mentioned by Geske et al,1 the relationship of tobacco to TAO has been known for decades. In an early series from Mayo Clinic, only 5 of 350 men (aged 25-55 years) with TAO were nonsmokers.3 In the discussion, Dr W. J. Mayo quipped: “On the whole, smoking seems a habit which has possibilities for harm, and has little to its credit.” Of course, this report from Mayo Clinic dates to 1931, long before most of the detrimental effects of tobacco use were known. However, as Geske et al1 point out, the misconception that tobacco dependence treatment is unsuccessful in patients with TAO is common. Quite the contrary, we found that smokers with TAO were no more tobacco dependent than smokers with coronary artery disease; thus, treatment should be aggressively pursued in these patients.4 We also observed that patients with TAO smoked fewer cigarettes per day than patients with coronary artery disease and were more likely to have made a serious attempt to stop in the past. Certainly for smokers with such a severe medical problem as TAO, residential treatment for tobacco dependence offers the best option to stop and remain abstinent from smoking.5 An overall 1-year smoking abstinence rate of 45% was reported after an 8-day residential treatment program.6 In patients who continue to smoke, TAO is relentlessly progressive and results in chronic and severe pain, gangrene, and autoamputation. Urinary tobacco alkaloids should be measured in patients with TAO who deny smoking to detect surreptitious smoking. Aggressive tobacco dependence treatment, including residential treatment, should be offered to patients with this disease as soon as possible. Richard D. Hurt, MD J. Taylor Hays, MD Mayo Clinic Rochester, MN 1. Geske JB, Calvin AD, McDonald FS. 37-year-old man with painful foot. Mayo Clin Proc. 2008;83(7):821-824. 2. Moyer TP, Charlson JR, Enger RJ, et al. Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Clin Chem. 2002; 48(9):1460-1471. 3. Barker N. The tobacco factor in thrombo-angiitis obliterans. Proc Staff Meet Mayo Clin. 1931;6(2):65-68. 4. Cooper LT, Henderson SS, Ballman KV, et al. A prospective, case-control study of tobacco dependence in thromboangiitis obliterans (Buerger’s disease). Angiology. 2006;57(1):73-78.
1188
Mayo Clin Proc.
•
5. Hooten WM, Bruns HK, Hays JT. Inpatient treatment of severe nicotine dependence in a patient with thromboangiitis obliterans (Buerger’s disease). Mayo Clin Proc. 1998;73(6):529-532. 6. Hays JT, Wolter TD, Eberman KM, Croghan IT, Offord KP, Hurt RD. Residential (inpatient) treatment compared with outpatient treatment for nicotine dependence. Mayo Clin Proc. 2001;76(2):124-133.
In reply: We appreciate the insightful points made by Hurt and Hays. We agree that diagnostic studies of tobacco use would augment the evaluation of TAO and could prove particularly helpful in cases such as the one we presented, in which tobacco use was initially denied. In our case, angiography was required for the diagnosis of TAO; when the patient was presented with the angiographic findings while his mother was absent, he admitted to ongoing tobacco use. Urinary tobacco alkaloids might well be of benefit for assessing smoking cessation at subsequent follow-up visits for this patient. Given the strong linkage between tobacco use and TAO, we continue to advocate smoking cessation. Hurt and Hays provide excellent examples of data that further support this approach. Jeffrey B. Geske, MD Andrew D. Calvin, MD, MPH Furman S. McDonald, MD, MPH Mayo Clinic Rochester, MN
Hysteroscopic Sterilization in Women With Pulmonary Vascular Disease To the Editor: We read with interest the recent article by Famuyide et al1 on hysteroscopic sterilization in women with severe cardiac disease. We were particularly interested in the inclusion of patients with pulmonary vascular disease, whom the authors rightly describe as having increased risk of poor outcomes related to general anesthesia.2 The cohort described in this study included primarily patients with structural heart disease or acquired cardiac disease and associated pulmonary hypertension. Patients with pulmonary arterial hypertension (PAH) associated with congenital left-to-right shunt have a better prognosis than those with idiopathic PAH or PAH with other associated conditions.3 We have found hysteroscopic sterilization to be successful in patients with idiopathic PAH as well as congenital heart disease–associated PAH. Our clinic is a referral center for pulmonary vascular disease. Similar to the cohort described by Famuyide et al,1 our patients are counseled against pregnancy because of poor maternal and fetal outcomes with PAH.4 Many of our patients are treated with endothelin receptor antagonists, which are potentially teratogenic; thus, these patients require either sterilization or 2 reliable methods of birth control. We have referred 6 patients with PAH for hysteroscopic sterilization; 2 patients were unable to undergo the procedure, one because tubal ostia were not visible and one because of a previous tubal pregnancy, a contraindication to the procedure. In the remaining 4 patients (Table), all of whom successfully underwent hysteroscopic sterilization, no procedure- or anesthesia-re-
October 2008;83:(10):1187-1189
•
www.mayoclinicproceedings.com
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.