- Email: [email protected]
Association between plasma homocysteine and extracranial carotid arterial disease in oldor persons
1. Hosking MC, BensonLN, Musewe NN, Dyck JD, Freedom RM. Transcatheter occlusion of the persistently patent ductus arteriosus occluder: forty-month follow up andprevalenceof residual shunting.Circulation 1991;84:2313-2317. 2. Khan MA, Yousef SA, Mullins CE, Sawyer W. Experience with 205 proceduresof transcatheterclosure of ductusarteriosusin 182patients,with special reference to residual shuntsand long term follow up. J Thorac Cardiovmc Surg 1992;104:1721-1727. 3. Latson LA, Hofschire PJ, Kugler JD, CheathamJP, Gumbiner CH, Danford DA. Transcatheter closure of patent ductus arteriosus in pediatric patients. J Pediatr 1989;115:549-553. 4. Gianturco C, Anderson JH, Wallace S. Mechanical devices for arterial occlusion. Am J Radio1 1975;124:428-435. 5. Llyod TR, Fedderly R, Mendelsohn AM, Sandhu SK, B&man RH III. Transcatheterocclusion of natent ductus arteriosus with Gianturco coils. Circulation 1993;88:1412-14iO. aMooleJW,GeorgeL,~kSEUathewson~,SpicerRL,U~K,Roth&ureofthesmau@ent man& CambierP.i, Slacktic, Kirby WC. Percutaneous ductusarteriosususingx&ding springcoils.J Am CoUCar& 1994,23:75%765.
7. Hijazi ZM, Geggel RL. Results of anterogradetranscatheterclosure of patent ductus arteriosus using single or multiple Gianturco coils: immediate and short term results. Am J Cardiol 1994;74:925-929. 8. Galal 0, De Mour M, Al Fadley F, Hijazi ZM. Transcatheterclosure of the patent ductusarteriosus: comparisonbetween the Rashkind occluder device and the antegradeGianturco coils technique.Am Hem J 1996;131:368-372. 9. Shim D, Fedderly RT, Be&man RH III, Ludomirsky A, Young ML, Schork MA, Lloyd TR. Follow up of coil occlusion of patent ductus arteriosus. J Am Cdl Cardiol 1996;28:207-211. 10. Cambier PA, Kirby WC, Wortham DC, Moore JW. Percutaneousclosure of the small (< 2.5 mm) patent ductus artcriosus using coil embolization. Am J Cardiol 1992;69:815-816. 11. Tometzki AJP, Walsh KP, Arnold R, Peart I, Bu’lock FA, Snxram N, Abdulhamed JM, Godman MJ. Tramcatheter occlusion of the patent ductus arteriosus with Cook detachablecoils. Cardiol Young 1996;6(suppll):S6. 12. Fadley R, Halees Z, Galal 0, Kumar N, Wilson N. Left pulmonary artery stenosis:seriouscomplication of transcatheterocclusion of the persistentarterial duct (lett). Lancet 1993;341:559-560.
AssociatCon Between Plasma Homocysteine Extracranial Carotid Arterial Disease in Older Wilbert
S. Aronow,
lasma homocysteine is a risk factor for arteriosclerotic vasP cular disease.’ Selhub et al2 reported
MD, Chul Ahn, PhD, and Myron
TABLE I Association Between and 40% to 100% Extracroniol
R. Schoenfeld,
and Persows MD
Plasma Homocysteine, Vitamin 812, and Foiate Levels Corotid Arterial Disease (ECAD) in 12 1 Older Men
40% to 100% ECXD 0% to 39% ECAD in 418 older men and 623 older (n = 99) p Value (n = 22) women in the Framingham Heart a0 -c 9 NS 81 +8 Study that plasma homocysteine Age b) Homocysteine (pmol/L) 1926 1424 .0.003 was a risk factor for extracranial caVitamin 812 (rig/L) 454 + 215 553 + 154 0.052 rotid arterial disease (ECAD). We Folote (/lg/L) 6.3 + 2.1 9.5 + 3.2 0.0001 are reporting data showing an asIncreased homocysteine 1 o/22 (45%) 20/99 (20%) 0.013 (> 17 pmol/L) sociation between plasma homocysLow or indeterminate vitamin 812 3/22 (14%) 2/99 (2%) 0.041 teine level and 40% to 100% ECAD (<200 rig/L) in 121 older men and 279 older women in a long-term health care facility. 80% to 99% reduction; and V,, 0 m/s (no Doppler ... signal on ~2 separate tests) = 100% reduction. We investigated, in a prospective study, the asBlood was drawn in the fasting state from 400 sociation between plasma homocysteine, vitamin persons to determine plasma vitamin B12 and folate B12,and folate levels with the prevalence of 40% to levels by SmithKline Beecham Clinical Laborato100% ECAD detected by bilateral carotid duplex ul- ries, Inc. (Syosset, New York) and to determine trasonograms in 121 men and 279 women (mean age plasma homocysteine levels by Specialty Laborato81 + 8 years; range 60 to 99) in a long-term health ries, Inc. (Santa Monica, California). No patient was care facility. Bilateral carotid duplex ultrasonograms in renal failure or was taking phenytoin, carbamawere obtained as previously described with an Inter- zepine, colestipol, niacin, isoniazide, or hydralazine. spec XL machine (Interspec Inc., Reedsville, Penn- Plasma vitamin B12 and folate levels were detersylvania) using a 7.5MHz transducer with combined mined by using the Abbott IMx B12 assay and the 2-dimensional, real-time, and pulsed or high-pulse Abbott IMx folate assay (Abbott Diagnostics, Abbott frequency Doppler capabilities.3 The severity of in- Park, Illinois)? Plasma homocysteine levels were deternal or common carotid atherosclerotic obstruction termined by a high-performance liquid chromatogwas semiquantified by using conventional Doppler raphy assay.5 Normal plasma homocysteine levels criteria: maximal velocity (V,,) ~0.8 m/s = ~40% are 4.0 to 17.0 pmol/L. Normal plasma vitamin B12 arterial luminal diameter reduction; V,, 0.80 to 1.75 levels are >200 rig/L. Indeterminate plasma vitamin m/s = 40% to 80% reduction; V,, > 1.75 m/s = B12levels are 160 to 200 rig/L. Low plasma vitamin B12levels are < 160 rig/L. Normal plasma folate levels are 3 to 19 pg/L. For analyses comparing 2 From the Hebrew Hospital Home, Bronx, New York; the Department groups, Fisher’s exact or &i-square tests were apof Geriatrics and Adult Development, Mount Sinai School of Medicine, New ‘fork, New York; and the Division of Clinical Epidemiolplied to dichotomous variables, and Student’s t tests ogy, University of Texas Medical School at Houston, Houston, Texas. were used for continuous variables. Dr. Aronow’s address is: Hebrew Hospital Home, 801 Co-op City Tables I and II show the association between Boulevard, Bronx, New York 10475. Manuscript received October plasma homocysteine, vitamin B12, and folate levels, 3 1, 1996; revised manuscript received and accepted January 27, 1997. and 40% to 100% ECAD in 121 older men (Table I)
1432
o 1997 by Excerpta Medico, All rights reserved.
Inc.
0002-9149/97/Q 17.00 PII SOOO2.9149(97)00161-6
TABLE II Association Between and 40% to 100% Extracranial
Plasma Homocysteine, Vitamin B12, and Folate Levels Carotid Arterial Disease (ECAD) in 279 Older
Woman . -. -.
Age(yrsl Homocysteine (pmol/L) Vitamin 812 (rig/L) Folote (pg/L) lncreosed homocysteine
I> 17 vmol/LI Low or inheteimkate (<200 rig/L)
vitamin
812
40% to 100% ECAD (n = 43)
0% to 39% ECAD (n = 236)
p Value
83 +9 17+4 443 + 126 6.3 r 1.4 17/43 (40%)
82 ? 8 13 -c5 533 2 157 9.5 + 3.1 43/236 (18%)
NS <0.0001 0.0005 0.0001 0.002
2/43 (5%)
3/236 (1%)
NS
and in 279 older women (Table II). None of the 400 persons (0%) had a low (<3 &L) plasma folate level. ...
The Framingham Heart Study demonstrated that elevated plasma homocysteine levels and low plasma folate and vitamin B6 levels were associated with an increased risk of ECAD in their older population. Our data demonstrated that high plasma homocysteine levels and low plasma folate and vitamin BIz levels were associated with a higher
- prevalence of 40% to 100% ECAD in our older men and women. Elevated plasma homocvsteine levels were orbservedin 45% of our older men with 40% to 100% ECAD versus 20% of our older men with 0% to 39% ECAD, and in 40% of our older women with 40% to 100% ECAD versus 18% of our older women with 0% to 39% ECAD.
1. Boushey CJ, Beresford SAA, Omenn GS, Motolsky AG. A quantitative assessmentof plasma homocysteine as a risk factor for vascular disease.Probable tenetits of increasing folic acid intakes. JAMA 1995;274:1049-1057. 2. Selhub J, JacquesPF, Bostom AG, D’Agostino RB, Wilson PWF, Belanger AJ, O’Leary DH, Wolf PA, Schaefer EJ, Rosenberg IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis.N Engl J Med 1995;332:286-291. 3. Aronow WS, Ahn C, Schoenfeld MR. Risk factors for extracranial internal or common carotid arterial disease in elderly patients. Am J Cardiol 1993;71:1479-1481. 4.L.eeDSC. Griffiths BW. Human semmvitaminJ& assaymethods-areview. Clin Biochn 1985;18:261-266. 5. Ueland PM, Refsum H, Stabler SP, Malinow MR. Andersson A, Allen RH. Total homocysteinein plasmaor serum:methodsand clinical applications. Clin them 1993;39:1764-1779.
Prevalence and Pro nestic Si nificance Cardiac Mobi f e Thromb I in Acute Pulmenary Embolism Franc0 Casazza,
MD,
Amedeo
Bongarzoni,
MD, Fabrizio
ost echocardiographic reports on right-sided cardiac mobile thrombi, “in transit” from the systemic venous system are case reportsle5 or case series ‘-12 in which clots were detected either during an acute pulmonary embolism or found incidentally. The largest studies are meta-analyses13*14or cases collected by questionnaire,15 but the populations are heterogeneous because subjects who harbored immobile thrombi were included, the hemodynamic severity of pulmonary embolism was variable, and the time interval between hospital admission and echocardiographic examination was not mentioned. The prognostic significance of right-sided mobile thrombi and the best therapeutic approach remains uncertain, although thrombolytic agents have been advocated for management of “in transit” c10ts.‘“‘~ Furthermore, their role in patients with massive pulmonary embolism has not been carefully elucidated. ... In the past 10 years, we examined by echocardiography 151 patients (94 women and 57 men, mean From the Division of Cardiolo y San Corlo Hospital, via Pio 2”, 3; jl Milan, Italy. Dr. Casazza’s o dress IS: wa Nlkolaievka 12; 20152 Milan, Italy. Manuscript received June 13, 1996; revised manuscript received and accepted January 2 1, 1997.
81997 by Excerpta Medica, Inc. All rights reserved.
Centonze,
o# Ri ht=Sided Mass t ve MD, and Mario
Morpurgo,
MD
age 66 2 19 years), in whom the clinical suspicion of pulmonary embolism was subsequently confirmed by lung perfusion scanning (in most cases), pulmonary angiography, or autopsy. To consider a population as homogeneous as possible, only patients with massive pulmonary embolism, undergoing echocardiography within 24 hours from admission, entered the study. Pulmonary embolism was graded massive by evidence of right ventricular overload, namely an abnormal increase of right ventricular/left ventricular end-diastolic diameter ratio in at least 2 echocardiographic views. Reference values for such measurements have been reported by Casazza et al.” One hundred thirty patients, fulfilling the abovementioned criteria, constitute our patient population. In 35% of cases, the echocardiogram was obtained in the emergency department and in 83% it was performed within 6 hours. Color Doppler imaging was accomplished in 72% of cases: the velocity of tricuspid regurgitation flow profile was assessed by continuous-wave Doppler. Diagnosis of in transit right-sided thrombi was made when a worm-like, elongated mass15exhibited ~2 of the following patterns: (1) high and chaotic motility, (2) continuous changing shape, and (3) prolapse into the right ventricle. Dyspnea was present in 78% of cases, systemic arterial blood pressure 190 mm Hg or shock 0002-9 149/97/$17.00 PII SOOO2-9149(97)00162-g
1433
7. Hijazi ZM, Geggel RL. Results of anterogradetranscatheterclosure of patent ductus arteriosus using single or multiple Gianturco coils: immediate and short term results. Am J Cardiol 1994;74:925-929. 8. Galal 0, De Mour M, Al Fadley F, Hijazi ZM. Transcatheterclosure of the patent ductusarteriosus: comparisonbetween the Rashkind occluder device and the antegradeGianturco coils technique.Am Hem J 1996;131:368-372. 9. Shim D, Fedderly RT, Be&man RH III, Ludomirsky A, Young ML, Schork MA, Lloyd TR. Follow up of coil occlusion of patent ductus arteriosus. J Am Cdl Cardiol 1996;28:207-211. 10. Cambier PA, Kirby WC, Wortham DC, Moore JW. Percutaneousclosure of the small (< 2.5 mm) patent ductus artcriosus using coil embolization. Am J Cardiol 1992;69:815-816. 11. Tometzki AJP, Walsh KP, Arnold R, Peart I, Bu’lock FA, Snxram N, Abdulhamed JM, Godman MJ. Tramcatheter occlusion of the patent ductus arteriosus with Cook detachablecoils. Cardiol Young 1996;6(suppll):S6. 12. Fadley R, Halees Z, Galal 0, Kumar N, Wilson N. Left pulmonary artery stenosis:seriouscomplication of transcatheterocclusion of the persistentarterial duct (lett). Lancet 1993;341:559-560.
AssociatCon Between Plasma Homocysteine Extracranial Carotid Arterial Disease in Older Wilbert
S. Aronow,
lasma homocysteine is a risk factor for arteriosclerotic vasP cular disease.’ Selhub et al2 reported
MD, Chul Ahn, PhD, and Myron
TABLE I Association Between and 40% to 100% Extracroniol
R. Schoenfeld,
and Persows MD
Plasma Homocysteine, Vitamin 812, and Foiate Levels Corotid Arterial Disease (ECAD) in 12 1 Older Men
40% to 100% ECXD 0% to 39% ECAD in 418 older men and 623 older (n = 99) p Value (n = 22) women in the Framingham Heart a0 -c 9 NS 81 +8 Study that plasma homocysteine Age b) Homocysteine (pmol/L) 1926 1424 .0.003 was a risk factor for extracranial caVitamin 812 (rig/L) 454 + 215 553 + 154 0.052 rotid arterial disease (ECAD). We Folote (/lg/L) 6.3 + 2.1 9.5 + 3.2 0.0001 are reporting data showing an asIncreased homocysteine 1 o/22 (45%) 20/99 (20%) 0.013 (> 17 pmol/L) sociation between plasma homocysLow or indeterminate vitamin 812 3/22 (14%) 2/99 (2%) 0.041 teine level and 40% to 100% ECAD (<200 rig/L) in 121 older men and 279 older women in a long-term health care facility. 80% to 99% reduction; and V,, 0 m/s (no Doppler ... signal on ~2 separate tests) = 100% reduction. We investigated, in a prospective study, the asBlood was drawn in the fasting state from 400 sociation between plasma homocysteine, vitamin persons to determine plasma vitamin B12 and folate B12,and folate levels with the prevalence of 40% to levels by SmithKline Beecham Clinical Laborato100% ECAD detected by bilateral carotid duplex ul- ries, Inc. (Syosset, New York) and to determine trasonograms in 121 men and 279 women (mean age plasma homocysteine levels by Specialty Laborato81 + 8 years; range 60 to 99) in a long-term health ries, Inc. (Santa Monica, California). No patient was care facility. Bilateral carotid duplex ultrasonograms in renal failure or was taking phenytoin, carbamawere obtained as previously described with an Inter- zepine, colestipol, niacin, isoniazide, or hydralazine. spec XL machine (Interspec Inc., Reedsville, Penn- Plasma vitamin B12 and folate levels were detersylvania) using a 7.5MHz transducer with combined mined by using the Abbott IMx B12 assay and the 2-dimensional, real-time, and pulsed or high-pulse Abbott IMx folate assay (Abbott Diagnostics, Abbott frequency Doppler capabilities.3 The severity of in- Park, Illinois)? Plasma homocysteine levels were deternal or common carotid atherosclerotic obstruction termined by a high-performance liquid chromatogwas semiquantified by using conventional Doppler raphy assay.5 Normal plasma homocysteine levels criteria: maximal velocity (V,,) ~0.8 m/s = ~40% are 4.0 to 17.0 pmol/L. Normal plasma vitamin B12 arterial luminal diameter reduction; V,, 0.80 to 1.75 levels are >200 rig/L. Indeterminate plasma vitamin m/s = 40% to 80% reduction; V,, > 1.75 m/s = B12levels are 160 to 200 rig/L. Low plasma vitamin B12levels are < 160 rig/L. Normal plasma folate levels are 3 to 19 pg/L. For analyses comparing 2 From the Hebrew Hospital Home, Bronx, New York; the Department groups, Fisher’s exact or &i-square tests were apof Geriatrics and Adult Development, Mount Sinai School of Medicine, New ‘fork, New York; and the Division of Clinical Epidemiolplied to dichotomous variables, and Student’s t tests ogy, University of Texas Medical School at Houston, Houston, Texas. were used for continuous variables. Dr. Aronow’s address is: Hebrew Hospital Home, 801 Co-op City Tables I and II show the association between Boulevard, Bronx, New York 10475. Manuscript received October plasma homocysteine, vitamin B12, and folate levels, 3 1, 1996; revised manuscript received and accepted January 27, 1997. and 40% to 100% ECAD in 121 older men (Table I)
1432
o 1997 by Excerpta Medico, All rights reserved.
Inc.
0002-9149/97/Q 17.00 PII SOOO2.9149(97)00161-6
TABLE II Association Between and 40% to 100% Extracranial
Plasma Homocysteine, Vitamin B12, and Folate Levels Carotid Arterial Disease (ECAD) in 279 Older
Woman . -. -.
Age(yrsl Homocysteine (pmol/L) Vitamin 812 (rig/L) Folote (pg/L) lncreosed homocysteine
I> 17 vmol/LI Low or inheteimkate (<200 rig/L)
vitamin
812
40% to 100% ECAD (n = 43)
0% to 39% ECAD (n = 236)
p Value
83 +9 17+4 443 + 126 6.3 r 1.4 17/43 (40%)
82 ? 8 13 -c5 533 2 157 9.5 + 3.1 43/236 (18%)
NS <0.0001 0.0005 0.0001 0.002
2/43 (5%)
3/236 (1%)
NS
and in 279 older women (Table II). None of the 400 persons (0%) had a low (<3 &L) plasma folate level. ...
The Framingham Heart Study demonstrated that elevated plasma homocysteine levels and low plasma folate and vitamin B6 levels were associated with an increased risk of ECAD in their older population. Our data demonstrated that high plasma homocysteine levels and low plasma folate and vitamin BIz levels were associated with a higher
- prevalence of 40% to 100% ECAD in our older men and women. Elevated plasma homocvsteine levels were orbservedin 45% of our older men with 40% to 100% ECAD versus 20% of our older men with 0% to 39% ECAD, and in 40% of our older women with 40% to 100% ECAD versus 18% of our older women with 0% to 39% ECAD.
1. Boushey CJ, Beresford SAA, Omenn GS, Motolsky AG. A quantitative assessmentof plasma homocysteine as a risk factor for vascular disease.Probable tenetits of increasing folic acid intakes. JAMA 1995;274:1049-1057. 2. Selhub J, JacquesPF, Bostom AG, D’Agostino RB, Wilson PWF, Belanger AJ, O’Leary DH, Wolf PA, Schaefer EJ, Rosenberg IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis.N Engl J Med 1995;332:286-291. 3. Aronow WS, Ahn C, Schoenfeld MR. Risk factors for extracranial internal or common carotid arterial disease in elderly patients. Am J Cardiol 1993;71:1479-1481. 4.L.eeDSC. Griffiths BW. Human semmvitaminJ& assaymethods-areview. Clin Biochn 1985;18:261-266. 5. Ueland PM, Refsum H, Stabler SP, Malinow MR. Andersson A, Allen RH. Total homocysteinein plasmaor serum:methodsand clinical applications. Clin them 1993;39:1764-1779.
Prevalence and Pro nestic Si nificance Cardiac Mobi f e Thromb I in Acute Pulmenary Embolism Franc0 Casazza,
MD,
Amedeo
Bongarzoni,
MD, Fabrizio
ost echocardiographic reports on right-sided cardiac mobile thrombi, “in transit” from the systemic venous system are case reportsle5 or case series ‘-12 in which clots were detected either during an acute pulmonary embolism or found incidentally. The largest studies are meta-analyses13*14or cases collected by questionnaire,15 but the populations are heterogeneous because subjects who harbored immobile thrombi were included, the hemodynamic severity of pulmonary embolism was variable, and the time interval between hospital admission and echocardiographic examination was not mentioned. The prognostic significance of right-sided mobile thrombi and the best therapeutic approach remains uncertain, although thrombolytic agents have been advocated for management of “in transit” c10ts.‘“‘~ Furthermore, their role in patients with massive pulmonary embolism has not been carefully elucidated. ... In the past 10 years, we examined by echocardiography 151 patients (94 women and 57 men, mean From the Division of Cardiolo y San Corlo Hospital, via Pio 2”, 3; jl Milan, Italy. Dr. Casazza’s o dress IS: wa Nlkolaievka 12; 20152 Milan, Italy. Manuscript received June 13, 1996; revised manuscript received and accepted January 2 1, 1997.
81997 by Excerpta Medica, Inc. All rights reserved.
Centonze,
o# Ri ht=Sided Mass t ve MD, and Mario
Morpurgo,
MD
age 66 2 19 years), in whom the clinical suspicion of pulmonary embolism was subsequently confirmed by lung perfusion scanning (in most cases), pulmonary angiography, or autopsy. To consider a population as homogeneous as possible, only patients with massive pulmonary embolism, undergoing echocardiography within 24 hours from admission, entered the study. Pulmonary embolism was graded massive by evidence of right ventricular overload, namely an abnormal increase of right ventricular/left ventricular end-diastolic diameter ratio in at least 2 echocardiographic views. Reference values for such measurements have been reported by Casazza et al.” One hundred thirty patients, fulfilling the abovementioned criteria, constitute our patient population. In 35% of cases, the echocardiogram was obtained in the emergency department and in 83% it was performed within 6 hours. Color Doppler imaging was accomplished in 72% of cases: the velocity of tricuspid regurgitation flow profile was assessed by continuous-wave Doppler. Diagnosis of in transit right-sided thrombi was made when a worm-like, elongated mass15exhibited ~2 of the following patterns: (1) high and chaotic motility, (2) continuous changing shape, and (3) prolapse into the right ventricle. Dyspnea was present in 78% of cases, systemic arterial blood pressure 190 mm Hg or shock 0002-9 149/97/$17.00 PII SOOO2-9149(97)00162-g
1433