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Death in opera: A case study, “Tales of Hoffman” — Antonia
But there are other works in which the cause of death onstage is Repetfusion No Reperfusion less apparent. An opera in point is (n = 121 (n = 4) “Tales of Hoffman” by Jacques OfB-TG (SD) (@ml) 256 (78) 187 (43) fenbach, and in particular the third TXB-2 (SD) (pe/ml) 269 (94) 117 (38) or “Antonia” act. E-TG = p thromboglobulin; TXB-2 = thromtwxane-B-2. “Tales” was Offenbach’s last opera and unfinished when he died in 1880 of complications of gout and heart disease. His librettists, Jules thromboglobulin (B-TG) levels be consistent with our previously Barbier and Michel Carre, adapted measured at the end of brief SK presented data. their own stage play of 185 1 for his MHdD8udwudy,MD musical setting; the stage play was infusion and therefore did not find Jdm HIM, MD an explanation for our previous obbased on 3 stories by the German ZottanRoda,mo KdmM Rrk, MD author, musician and conductor, servations on increased B-TG levels Debrecen, Hungary after SK infusion.* painter and designer, law student 2 April 1992 The interpretation and compariand Berlin Supreme Court councilson of these 2 studies needs great 1. Bertolino G, Noris P, Previtali M, lor E. T. A. Hoffman, perhaps caution. First, we did not measure GambaG, FerrarioM, Montani N, Bal- more famous for his fantastical stoB-TG concentrations before SK in- duini CL. Plateletfunction after in vivo ry of the “Nutcracker and Mousefusions and therefore could not andin vitro treatmentwith thrombolytic king.” A prologue sets the tales: the make any conclusions on the early agents.Am J Cardiol 1992;69:457-461. narrator, Hoffman himself, awaits UdvardyM, HBrsfalviJ, BodaZ, Rak postinfusion changes of B-TG. The 2. K. Thromboticchangesin haemostasishis current flame, a soprano, and to mean lag period between the onset following intravenous Streptokinase pass the time, he regales his fellow of clinical signs and the initiation treatment for acute myocardialinfarc- students with his stories. In each of of thrombolytic therapy was >3 tion. Thromb Haemost 1990;63:146-147. the 3 acts that follows, Hoffman hours; thus, the difference between 3. FitzgeraldDJ, CatellaF, RoyL, Fitz- tells of an episode in his life in the timing of the 2 examinations geraldGA. Marked plateletactivationin which he loses his beloved to a sinisin pa- ter figure, the devil in disguise. In may have a greater impact and vivoafter intravenousstreptokinase more meaningful effect on the re- tients with acute myocardialinfarction. the first act, he loses Olympia, a sults, as was suggested by Berto- Circulation 1988;1:142-150. mechanical doll, to qoppelius, in 4. Eisenberg PR. Roleof newanticoagu- the second, he loses a Venetian lino. asadjunctivetherapyduringthromOur later results suggest that our lants courtesan, Giulietta, to Dappertutbolysis.Am J Caidiol1991;67:19A-24A. findings of increased platelet acti- 5. MaruyamaM, FarberNE, Vercellotti to, and in the third, Antonia dies vation after SK treatment of AM1 GM, JacobHS, GrossGJ. Evidencefor a after the machinations of Dr. Mirmay at least in part be regarded as a role of platelet activating factor in the acle. consequence of a reperfusion/reIt is the third story (act) that repathogenesis of irreversiblebut not reoxygenation injury (see table). versiblemyocardialinjury after reper- quires forensic analysis. In 1819, The increase of the plasmatic lev- fusionin dogs.Am Heart J 1990;120: Hoffman published “Rath Kres510-524. el of von Willebrand factor antigen, pel” (Councillor Crespel),’ in together with the reduction of an- Death in Opera: A Care Study, which a young woman sings to the tithrombin-III antigen concentratune of a violin made by her father, “Tales of Hoffman’* - Antonia tions and protein C activity, was an elected official and amateur also more significant in the reperfuThe investigation of death on the craftsman; as she reaches the topsion group. (B-TG and the other pa- operatic stage calls for the talents of most note of her song, his prized rameters did not change consideraa forensic pathologist. In the stan- Cremonese violin shatters and she bly in a patient who received 5-day dard repertory, mayhem is ram- dies. The librettists made some changes for Offenbach’s opera. In SK infusion therapy for inferior ca- pant. An opera in point is “Tosca” by Giacomo Puccini. By curtain fall Robert Lawrence’s analysis,2 they val vein thrombosis.) In many cases, platelet activa- at the end of the third act, the 3 “introduced the most effectively tion may be the consequence of re- principals are dead: the baritone evil of characters, the slimy Dr. perfusion and reoxygenation itself Scarpia murdered (a knife in his Miracle who, entering through the after SK treatment of AM1 (i.e., back) by Tosca, the tenor Cavara- walls when the door is denied him, increased thromboxane metabodossi shot by firing squad, and the induces Antonia to sing herself to lism,*13 thrombin-induced platelet soprano Tosca having leapt to her death while accompanying her on a activation,4 and release of plateletdeath from the parapet of the Cas- macabre violin.” activating factor and other biologitel Sant’Angelo. It is, for the audiBy what cause could singing incally active compounds5). The high ence, an extremely satisfying eve- duce the death of a young woman incidence of thrombotic reocclu- ning, because of the glorious music who has inherited from her mother, sions after the initial success of that accompanies these homicides/ an opera singer who died under similar circumstances, a beautiful thrombolytic therapy also seems to suicide. Treatment of Acute Myocardial Infarction with Streptokinase
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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 70
SEPTEMBER 15, 1992
voice and a frail physique? Offenbath helps the forensic pathologist here. It is near the end of the act, and Dr. Miracle appears magically to the consternation of Crespel and Hoffman who fear the doctor’s evil ministrations. Dr. Miracle sings: “Nineteen. Glorious springtime of life. And now, let me take your pulse. . . Sh! Quiet while I count. . . Her pulse - very uneven and fast (inegal et vif). A dangerous symptom! Now sing! Now sing!” In the score, Offenbach has set the accompaniment in triplets (in duple rhythm, 3 sixteenth notes followed by a sixteenth note pause or rest) beginning with the taking of Antonia’s pulse (stage direction) by Dr. Miracle. Antonia sings and dies, and another of Hoffman’s loves is lost. It should be noted that the use of musical values to represent the pulse goes back to Herophilus, a physician and contemporary of Aristotle in the fourth century BC, who interpreted thepulse according to “its rhythm or cadence which he likened to musical time and measures of verse.“3 In Nancy, France, in 1747 (with a second edition in 1769, in Amsterdam), Francois Nicolas Marquet published a book devoted to his special musical notation representing the varieties of palpated pulses.4 “He stated that those accustomed to play on the lute made the best judges of the pulse!“3 Antonia has an inherited condition that under stress manifests itself as a cardiac arrhythmia followed by sudden death. Although the following discussion is speculative given the limited evidence, I believe, for the forensic pathologist, the differential diagnosis includes: (a) hereditary prolongation of the Q-T interval, (b) “malignant” hypertrophic cardiomyopathy, and (c) mitral valve prolapse. Hereditary prolongation of the Q-T interval is a non-sex-linked autosomal dominant inherited condition in which the patient is prone to syncope, with ventricular fibrillation and sudden death. A few such families have been described,5 some with associated neural deafness (the Romano-Ward syndrome,
which is of recessive inheritance). But these are rare conditions, and many subjects affected have lived into the fifth decade. “Malignant” hypertrophic cardiomyopathy has been characterized by sudden and unexpected death as the initial manifestation of cardiac disease,6 often in the second or third decade of life. However, a third of these patients with sudden death have had chronic progressive heart failure or peripheral thromboembolic events. There are no defined patterns of inheritance. Mitral valve prolapse was first described in the medical literature in 1963 when Barlow et al7 reported on the clinical features associated with systolic clicks originating in the mitral apparatus. There is evidence to suggest that mitral valve prolapse is inherited as an autosoma1 dominant condition8 and may also be associated with the inheritance, as an autosomal dominant, of a physical habitus characterized by narrow anterior posterior chest dimension and a longer arm span (a thin and frail appearance, perhaps a form fruste of the Marfan syndrome) .9 Patients with the mitral valve prolapse syndrome may complain of shortness of breath and fatigue, and may be frail in spirit as well as in habitus. Cardiac arrhythmias and conduction abnormalities may be frequent, with both atria1 and ventricular tachyarrhythmias welldescribed. Although the sudden death syndrome is rare, Chesler et allo reported 39 cases, predominantly women, in which 6 of 7 patients showed ventricular ectopy in electrocardiograms available before death. In their report, case 3 was a lQyear-old female who died suddenly and whose mother had died in similar circumstances at age 36. Kligfield et al” reviewed the literature and suggested that sudden death occurs more commonly in those patients with mitral valve prolapse who also have significant mitral regurgitation; these patients are also reported to have frequent and complex atria1 and ventricular arrhythmias. The incidence may be as high as 0.5% annually, suggesting up to 4,000 deaths of which two
thirds likely have hemodynamically significant mitral regurgitation and one third have no insufficiency. Whether increased plasma catecholamines related to stress (“Now sing! Now sing!“) or present as an associated state of autonomic dysfunction/imbalance may predispose subjects to ventricular ectopy or catastrophic arrhythmia, or both, is not known, but has been suggested. l2 Antonia sings and dies. An autopsy would show redundant mitral leaflets probably with annular dilatation, and myxomatous changes on microscopic examination. Antonia should have been treated with /3adrenergic blockers and could have then sung to her heart’s content to a sedate and regular accompaniment, if to the loss of the dramatic and tragic, requisite to grand opera. )nonrd 0. Dauber, MD New York, New York 9 April 1991
1. Selected Writings of ETA Hoffman, edited and translated by Kent LJ and Knight E. Chicago: University of Chicago Press, 1969:168-188. 2. Les Contes d’Hoffman, piano score, English version by Ruth and Thomas Martin, New York: G. Schirmer, 1959: v and 258-259. 3. Bedford DE. The ancient art of feeling the pulse. Er Heart J 1951;13:423-437. 4. Horine EF. An epitome of ancient pulse lore. Bull Hist Med 194l;lO: 209-249.
5. Roy PR, Emanuel R, Ismail SA, El Tayib MH. Hereditary prolongation of the Q-T interval, Genetic observations and management in three families with twelve affected members. Am J Curdiol 1976;37:237-243.
6. Maron BJ, Lipson LC, Roberts WC, Savage DD, Epstein SE. “Malignant” hypertrophic cardiomyopathy: identification of a subgroup of families with unusually frequent premature death. Am J Curdial 1978;41:1133-1140. 7. Barlow JB, Pocock NA, Marchant P, Denny M. The significance of late systolic murmurs. Am Heart J 1963;66:443-452. 8. Devereux RB, Brown WT, KramerFox R, Sachs I. Inheritance of mitral valve prolapse: effect of age and sex on gene expression. Ann Intern Med 1982; 97:826-832. 9. Schutte
JE, Gaffney FA, Blend L, Blomqvist CG. Distinctive anthropometric characteristics of women with mitral valve prolapse. Am J Med 1981;71: 533-538.
READERS’
COMMENTS
839
This can lead the readers to think Am J Chin Nutr 1990;51:1115. analyzers that the original equation is also 6. Mass6J. Portablecholesterol valid with SI units. I previously re- (ltr). JAMA 1990;264:1101. ported 2 publications where the un- 7. Mass6J. Calculationof low-densityliadapted version of the equation was poproteincholesterol(ltr). Arch Intern Med 1991;151:810. inappropriately applied.9*10 Haskell 8. MasstJ. Lipid profilesof olderwomen et al made the same mistake. Al- (ltr). J Am Diet Assoc 1991;91:1378. though the reported concentrations 9. MasstJ. Lipoprotein(a)levelsin black of LDL cholesterol for their first and white childrenand adolescents with study are correct (indicating that IDDM (ltr). Diabetes Care 1991;14: they only converted the final results 1108-l109. in SI units), the concentrations re- 10. Mass6J. Effectsof fish-oilingestion risk factors(ltr). Am J Seealso:HardingJ. JacquesOffenbach, ported for the 3 other studies are on cardiovascular A Biography.New York: Rivet-runPress, incorrect. They used the original Clin Nutr 1991;54:610-611. 1980;and Faris A. JacquesOffenbach. version of the Friedewald formula New York: Scribner’s,1980. after the other measurements were converted to SI units, resulting in REPLY: Yes, unfortunately in the an overestimation of LDL choles- calculation for studies 2 to 4 reportWber and terol (VLDL cholesterol being un- ed in our manuscript, the factor tAiho&d derestimated by using 5 instead of used for converting triglycerides to 2.18 as divisor). This error does not VLDL cholesterol in SI units was Haskell et al (1) studied the effect affect their final conclusions, since 5.0 instead of 2.18. In study 1, the of water-soluble dietary fiber of dif- the variations of triglyceride con- factor of 2.18 was correctly used. ferent sources on patients with hy- centrations were very similar be- As pointed out by Masse, this error percholesterolemia. To estimate tween each group so that the over- does not influence the results or low-density lipoprotein (LDL) cho- estimation was of the same order. I conclusions of these studies. On avlesterol, they used the Friedewald therefore reiterate my caution to in- erage, this error results in the mean formula.* This equation is based on vestigators and readers that before LDL cholesterol values we reported the fact that the majority of circu- using equations originally designed being approximately 9% higher in lating triglycerides (during fasting) to be used with conventional units SI units than they actuahy were. are transported by very low density with SI units, one must check if a For example, in study 3 (Table IV), lipoprotein (VLDL). The amount conversion factor is necessary. By the mean baseline values should of cholesterol bound to VLDL can the way, in Table III the change in have been 4.41 mmol/L instead of be estimated because of a relatively 4.76, and 3.88 mmol/L instead of triglycerides for their placebo constant proportion of cholesterol group should read +0.025 (instead 4.28 when the subjects were on the and triglycerides in VLDL. When of +0.25) mmol/L or 1.66% (in- fiber mixture, with the decrease betriglycerides and cholesterol con- stead of 16.6%). ing -0.53 mmol/L instead of centrations are expressed in mg/dL Jacques Mass& WD, msc -0.54, and the percentage change Quebec City, Quebec, Canada being 12.0% instead of the reported units, the Friedewald formula esti6 March1992 mates VLDL cholesterol by divid12.4. wwiunL.Hukdl,?m ing the concentration of triglycerPaloAlto, California 1. HaskellWL, SpillerGA, JensenCD, ides by 5. This is what Haskell et al EllisBK, GatesJE. Roleof water-soluble 13April 1992 claim to have done. Unfortunately, dietaryfiber in themanagement of elevatthey did not use the mg/dL units, edplasmacholesterolin healthysubjects. but rather the Systbme InternationAm J Cardiol 1992;69:433-439. al (SI) units. As I have reported on 2. FriedewaldWT, Levy RI, Fredericka number of other occasions,3-8 the sonDS. Estimationof low-densitylipo- In the article, “Transthoracic proteincholesterol in plasma,withoutuse High-Frequency Two-Dimensional divisor of the Friedewald equation becomes 2.18 instead of 5 with SI of the preparativeultracentrifuge.Clin Echocardiography, Doppler and units, because the molecular weight Chem 1972;18:499-502. Color Flow Mapping to Determine of cholesterol is different from the 3. Mass6J. Lipid profilesafter cardiac Anatomy and Blood Flow Patterns transplantation (ltr). Am J Cardiol1991; average molecular weight of tri- 68566. in the Distal Left Anterior Deglycerides. Although the majority 4. Mass6J. Changes in lipoproteinsdur- scending Coronary Artery” by Anof American investigators do their ing weight loss (ltr). N Engl J A4ed toinette Kenny and Leonard M. work in conventional units and con- 1989;320:668. Shapiro, in the May 15, 1992 issue vert the final results to SI units, this 5. Mass6J. Clinicalchemistryreference of the AJC, Figure 5A on page is rarely reported in their articles. intervalsfor healthyelderlysubjects(ltr). 1267 is mistakenly inverted. 10. Chesler E, King RA, Edwards JE. The myxomatous mitral valve and sudden death. Circulation 1983;67:632-639. 11. Kligfield P, Levy D, DevereuxRB, Savage DD. Arrhythmias and sudden deathin mitral valveprolapse. Am Heart J 1987;113:1298-1307. 12. BoudalasH, ReynoldsJC, Mazzaferri E, WooleyCF. Metabolicstudiesin mitral valveprolapsesyndrome:a neuroendocrine-cardiovascular process.Circulation 1980;61:1200-1205.
840
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
70
SEPTEMBER
15,
1992
-
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 70
SEPTEMBER 15, 1992
voice and a frail physique? Offenbath helps the forensic pathologist here. It is near the end of the act, and Dr. Miracle appears magically to the consternation of Crespel and Hoffman who fear the doctor’s evil ministrations. Dr. Miracle sings: “Nineteen. Glorious springtime of life. And now, let me take your pulse. . . Sh! Quiet while I count. . . Her pulse - very uneven and fast (inegal et vif). A dangerous symptom! Now sing! Now sing!” In the score, Offenbach has set the accompaniment in triplets (in duple rhythm, 3 sixteenth notes followed by a sixteenth note pause or rest) beginning with the taking of Antonia’s pulse (stage direction) by Dr. Miracle. Antonia sings and dies, and another of Hoffman’s loves is lost. It should be noted that the use of musical values to represent the pulse goes back to Herophilus, a physician and contemporary of Aristotle in the fourth century BC, who interpreted thepulse according to “its rhythm or cadence which he likened to musical time and measures of verse.“3 In Nancy, France, in 1747 (with a second edition in 1769, in Amsterdam), Francois Nicolas Marquet published a book devoted to his special musical notation representing the varieties of palpated pulses.4 “He stated that those accustomed to play on the lute made the best judges of the pulse!“3 Antonia has an inherited condition that under stress manifests itself as a cardiac arrhythmia followed by sudden death. Although the following discussion is speculative given the limited evidence, I believe, for the forensic pathologist, the differential diagnosis includes: (a) hereditary prolongation of the Q-T interval, (b) “malignant” hypertrophic cardiomyopathy, and (c) mitral valve prolapse. Hereditary prolongation of the Q-T interval is a non-sex-linked autosomal dominant inherited condition in which the patient is prone to syncope, with ventricular fibrillation and sudden death. A few such families have been described,5 some with associated neural deafness (the Romano-Ward syndrome,
which is of recessive inheritance). But these are rare conditions, and many subjects affected have lived into the fifth decade. “Malignant” hypertrophic cardiomyopathy has been characterized by sudden and unexpected death as the initial manifestation of cardiac disease,6 often in the second or third decade of life. However, a third of these patients with sudden death have had chronic progressive heart failure or peripheral thromboembolic events. There are no defined patterns of inheritance. Mitral valve prolapse was first described in the medical literature in 1963 when Barlow et al7 reported on the clinical features associated with systolic clicks originating in the mitral apparatus. There is evidence to suggest that mitral valve prolapse is inherited as an autosoma1 dominant condition8 and may also be associated with the inheritance, as an autosomal dominant, of a physical habitus characterized by narrow anterior posterior chest dimension and a longer arm span (a thin and frail appearance, perhaps a form fruste of the Marfan syndrome) .9 Patients with the mitral valve prolapse syndrome may complain of shortness of breath and fatigue, and may be frail in spirit as well as in habitus. Cardiac arrhythmias and conduction abnormalities may be frequent, with both atria1 and ventricular tachyarrhythmias welldescribed. Although the sudden death syndrome is rare, Chesler et allo reported 39 cases, predominantly women, in which 6 of 7 patients showed ventricular ectopy in electrocardiograms available before death. In their report, case 3 was a lQyear-old female who died suddenly and whose mother had died in similar circumstances at age 36. Kligfield et al” reviewed the literature and suggested that sudden death occurs more commonly in those patients with mitral valve prolapse who also have significant mitral regurgitation; these patients are also reported to have frequent and complex atria1 and ventricular arrhythmias. The incidence may be as high as 0.5% annually, suggesting up to 4,000 deaths of which two
thirds likely have hemodynamically significant mitral regurgitation and one third have no insufficiency. Whether increased plasma catecholamines related to stress (“Now sing! Now sing!“) or present as an associated state of autonomic dysfunction/imbalance may predispose subjects to ventricular ectopy or catastrophic arrhythmia, or both, is not known, but has been suggested. l2 Antonia sings and dies. An autopsy would show redundant mitral leaflets probably with annular dilatation, and myxomatous changes on microscopic examination. Antonia should have been treated with /3adrenergic blockers and could have then sung to her heart’s content to a sedate and regular accompaniment, if to the loss of the dramatic and tragic, requisite to grand opera. )nonrd 0. Dauber, MD New York, New York 9 April 1991
1. Selected Writings of ETA Hoffman, edited and translated by Kent LJ and Knight E. Chicago: University of Chicago Press, 1969:168-188. 2. Les Contes d’Hoffman, piano score, English version by Ruth and Thomas Martin, New York: G. Schirmer, 1959: v and 258-259. 3. Bedford DE. The ancient art of feeling the pulse. Er Heart J 1951;13:423-437. 4. Horine EF. An epitome of ancient pulse lore. Bull Hist Med 194l;lO: 209-249.
5. Roy PR, Emanuel R, Ismail SA, El Tayib MH. Hereditary prolongation of the Q-T interval, Genetic observations and management in three families with twelve affected members. Am J Curdiol 1976;37:237-243.
6. Maron BJ, Lipson LC, Roberts WC, Savage DD, Epstein SE. “Malignant” hypertrophic cardiomyopathy: identification of a subgroup of families with unusually frequent premature death. Am J Curdial 1978;41:1133-1140. 7. Barlow JB, Pocock NA, Marchant P, Denny M. The significance of late systolic murmurs. Am Heart J 1963;66:443-452. 8. Devereux RB, Brown WT, KramerFox R, Sachs I. Inheritance of mitral valve prolapse: effect of age and sex on gene expression. Ann Intern Med 1982; 97:826-832. 9. Schutte
JE, Gaffney FA, Blend L, Blomqvist CG. Distinctive anthropometric characteristics of women with mitral valve prolapse. Am J Med 1981;71: 533-538.
READERS’
COMMENTS
839
This can lead the readers to think Am J Chin Nutr 1990;51:1115. analyzers that the original equation is also 6. Mass6J. Portablecholesterol valid with SI units. I previously re- (ltr). JAMA 1990;264:1101. ported 2 publications where the un- 7. Mass6J. Calculationof low-densityliadapted version of the equation was poproteincholesterol(ltr). Arch Intern Med 1991;151:810. inappropriately applied.9*10 Haskell 8. MasstJ. Lipid profilesof olderwomen et al made the same mistake. Al- (ltr). J Am Diet Assoc 1991;91:1378. though the reported concentrations 9. MasstJ. Lipoprotein(a)levelsin black of LDL cholesterol for their first and white childrenand adolescents with study are correct (indicating that IDDM (ltr). Diabetes Care 1991;14: they only converted the final results 1108-l109. in SI units), the concentrations re- 10. Mass6J. Effectsof fish-oilingestion risk factors(ltr). Am J Seealso:HardingJ. JacquesOffenbach, ported for the 3 other studies are on cardiovascular A Biography.New York: Rivet-runPress, incorrect. They used the original Clin Nutr 1991;54:610-611. 1980;and Faris A. JacquesOffenbach. version of the Friedewald formula New York: Scribner’s,1980. after the other measurements were converted to SI units, resulting in REPLY: Yes, unfortunately in the an overestimation of LDL choles- calculation for studies 2 to 4 reportWber and terol (VLDL cholesterol being un- ed in our manuscript, the factor tAiho&d derestimated by using 5 instead of used for converting triglycerides to 2.18 as divisor). This error does not VLDL cholesterol in SI units was Haskell et al (1) studied the effect affect their final conclusions, since 5.0 instead of 2.18. In study 1, the of water-soluble dietary fiber of dif- the variations of triglyceride con- factor of 2.18 was correctly used. ferent sources on patients with hy- centrations were very similar be- As pointed out by Masse, this error percholesterolemia. To estimate tween each group so that the over- does not influence the results or low-density lipoprotein (LDL) cho- estimation was of the same order. I conclusions of these studies. On avlesterol, they used the Friedewald therefore reiterate my caution to in- erage, this error results in the mean formula.* This equation is based on vestigators and readers that before LDL cholesterol values we reported the fact that the majority of circu- using equations originally designed being approximately 9% higher in lating triglycerides (during fasting) to be used with conventional units SI units than they actuahy were. are transported by very low density with SI units, one must check if a For example, in study 3 (Table IV), lipoprotein (VLDL). The amount conversion factor is necessary. By the mean baseline values should of cholesterol bound to VLDL can the way, in Table III the change in have been 4.41 mmol/L instead of be estimated because of a relatively 4.76, and 3.88 mmol/L instead of triglycerides for their placebo constant proportion of cholesterol group should read +0.025 (instead 4.28 when the subjects were on the and triglycerides in VLDL. When of +0.25) mmol/L or 1.66% (in- fiber mixture, with the decrease betriglycerides and cholesterol con- stead of 16.6%). ing -0.53 mmol/L instead of centrations are expressed in mg/dL Jacques Mass& WD, msc -0.54, and the percentage change Quebec City, Quebec, Canada being 12.0% instead of the reported units, the Friedewald formula esti6 March1992 mates VLDL cholesterol by divid12.4. wwiunL.Hukdl,?m ing the concentration of triglycerPaloAlto, California 1. HaskellWL, SpillerGA, JensenCD, ides by 5. This is what Haskell et al EllisBK, GatesJE. Roleof water-soluble 13April 1992 claim to have done. Unfortunately, dietaryfiber in themanagement of elevatthey did not use the mg/dL units, edplasmacholesterolin healthysubjects. but rather the Systbme InternationAm J Cardiol 1992;69:433-439. al (SI) units. As I have reported on 2. FriedewaldWT, Levy RI, Fredericka number of other occasions,3-8 the sonDS. Estimationof low-densitylipo- In the article, “Transthoracic proteincholesterol in plasma,withoutuse High-Frequency Two-Dimensional divisor of the Friedewald equation becomes 2.18 instead of 5 with SI of the preparativeultracentrifuge.Clin Echocardiography, Doppler and units, because the molecular weight Chem 1972;18:499-502. Color Flow Mapping to Determine of cholesterol is different from the 3. Mass6J. Lipid profilesafter cardiac Anatomy and Blood Flow Patterns transplantation (ltr). Am J Cardiol1991; average molecular weight of tri- 68566. in the Distal Left Anterior Deglycerides. Although the majority 4. Mass6J. Changes in lipoproteinsdur- scending Coronary Artery” by Anof American investigators do their ing weight loss (ltr). N Engl J A4ed toinette Kenny and Leonard M. work in conventional units and con- 1989;320:668. Shapiro, in the May 15, 1992 issue vert the final results to SI units, this 5. Mass6J. Clinicalchemistryreference of the AJC, Figure 5A on page is rarely reported in their articles. intervalsfor healthyelderlysubjects(ltr). 1267 is mistakenly inverted. 10. Chesler E, King RA, Edwards JE. The myxomatous mitral valve and sudden death. Circulation 1983;67:632-639. 11. Kligfield P, Levy D, DevereuxRB, Savage DD. Arrhythmias and sudden deathin mitral valveprolapse. Am Heart J 1987;113:1298-1307. 12. BoudalasH, ReynoldsJC, Mazzaferri E, WooleyCF. Metabolicstudiesin mitral valveprolapsesyndrome:a neuroendocrine-cardiovascular process.Circulation 1980;61:1200-1205.
840
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
70
SEPTEMBER
15,
1992