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SNORING AS RISK FACTOR FOR HYPERTENSION AND ANGINA
1340 PROPORTION OF VARIABILITY EXPLAINED BY APO All FLANKING RESTRICTION SITE 1
(CALCULATED
1
AS IN REF
1
Msp I
2)
1
chromosome 11. On the other hand this RFLP explains 0 - 4% or less of the variability in weight and height. These results are similar to those reported for the role of apo-E polymorphisms.4,5 However, unlike the apo-E polymorphism, the Msp I RFLP does not represent allelic variation of the gene product itself. Whether theMsp I RFLP is in linkage disequilibrium with DNA sequences directly involved with apo-AII regulation or whether it defines one of several "loci" having moderate direct effects are issues yet to be resolved. on
Center for
Demographic and Population Genetics,
Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas 77030, USA
CRAIG L. HANIS RANAJIT CHAKRABORTY DAVID HEWETT-EMMETT
1. Falconer DS. Quantitative genetics. New York: Ronald 2. Daiger SP, Miller M, Chakraborty R. Heritability of
Press, 1960.
quantitative variation at the Genet 1984; 36: 663-76. 3. Boerwinkle E. The use of measured genotype information in the genetic analysis of quantitative phenotypes. PhD dissertation, University of Michigan, 1985. 4. Sing CF, Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 1985; 37: 268-85. 5. Robertson FW, Cumming AM. Effects of apoprotein E polymorphism on serum lipoprotein concentration. Arteriosclerosis 1985; 5: 283-92. group-specific component (Gc) locus. Am J Hum
SICK SINUS SYNDROME AND ADENOSINE
SIR,-Dr Dighton (May 18, p 1157), commenting on my hypothesis about a role for adenosine in the sick sinus syndrome (SSS) (April 6, p 786), recognises that the abnormality in sinoatrial node function persists after "complete" vagal and sympathetic block. Therefore autonomic influences, which he seems to consider important, are unlikely to be an essential factor in the pathophysiology of the syndrome. Because these influences are probably peripheral I cited only one reference in relation to the possible effects of adenosine on cardiac autonomic nerves. Dighton asks how adenosine relates to the possibly increased effects of autonomic manoeuvres in SSS patients. However, responses to forced inspiration and exercise were said not to differ between controls and patients in his own studies,I,2 and carotid sinus hypersensitivity is a disease entity distinct from SSS.3The Valsalva manoeuvre may produce slightly different effectsl,2 in patients with the syndrome but this may simply reflect the effects of increased vagal tone on a node already affected by the fundamental pathophysiological processes in the syndrome, whether or not they are adenosine mediated. Adenosine could perhaps account for any enhanced vagal responses if its effect of post-junctional enhancement4of responses to acetylcholine were greater in patients with the SSS than its effect of pre-junctional inhibition. However, abnormalities of sinoatrial function persist in the presence of autonomic blockade, so any effect of adenosine on acetylcholine would be peripheral to the "intrinsic" abnormality of sinoatrial function. Dighton’s statement that he found responses to prostigmine to be greatly reduced in patients with sinoatrial disease contradicts his own comparisons of patients and controls ("differences between the drop in atrial rate and the rate of change of atrial rate fail to reach significant levels",and "no significant difference could be shown between the group with sinoatrial block and the controls"2). This discrepancy seriously undermines the possible relevance of the related comments in his letter. Dighton asks for histochemical evidence for the adenosine5 hypothesis. The in-vivo half-life of adenosine is a few second. Cardiac ischaemia causes adenosine release,and a similar release might occur post mortem so cardiac adenosine concentrations post
be related to the in-vivo situation in patients with SSS. Sinoatrial node biopsy would be unethical. Dighton suggests a role for cholinesterase and, by implication, acetylcholine in ischaemic nodal block. Aminophylline does not affect atrioventricular block produced by acetylcholine, but does antagonise block produced by adenosine or ischaemia.7 Thus adenosine would seem to be a stronger candidate as a possible mediator of ischaemic nodal block than acetylcholine. In his fourth paragraph Dighton asks for the adenosine hypothesis to explain observations unrelated to the heart in SSS. This seems unreasonable.
mortem cannot
Department of Pharmacology and Therapeutics, College of Medicine, University of Wales, Heath Park, CardiffCF4 4XN 1. 2. 3.
ANDREW H. WATT
Dighton DH. Sinus bradycardia: Autonomic influences and clinical assessment. Br Heart J 1974; 36: 791-97. Dighton DH. Sinoatrial block: Autonomic influences and clinical assessment. Br Heart J 1975; 37: 321-25. Zipes DP. Specific arrhythmias: Diagnosis and treatment. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. Philadelphia: WB Saunders, 1984:
683-743. 4. Gustaffson L. Influence of adenosine on responses to vagal nerve stimulation in the anaesthetised rabbit. Acta Physiol Scand 1981, 111: 263-68. 5. Klabunde RE. Dipyridamole inhibition of adenosine metabolism in human blood. Eur J Pharmacol 1983; 93: 21-26. 6. Fox AC, Reed GE, Kaltman AJ, Silk BB. Release of adenosine from human hearts during angina induced by rapid atrial pacing. J Clin Invest 1974; 53: 1447-57. 7. Belardinelli L, Belloni FL, Rubio R, Berne RM. Atrioventricular conduction disturbances during hypoxia: possible role of adenosine in rabbit and guinea pig heart. Circ Res 1980; 47: 684-91.
SNORING AS RISK FACTOR FOR HYPERTENSION AND ANGINA
SIR,-Dr Koskenvuo and colleagues (April 20, p 893) record an association between snoring, hypertension, and angina pectoris. Snoring is three times more common in the obese than in the nonobese,l which is consistent with the finding that obstructive sleep apnoea
syndrome is more common in the obese!-3 and excess body
weight and blood pressure are also related4 5-in short, snoring, obesity, hypertension, ischaemic episodes, and obstructive sleep apnoea are all interrelated.4-6 However, I doubt if snoring is a risk factor for angina. We have done sleep studies in 32 patients with morbid obesity and noted obstructive sleep apnoea in 12,88 ofwhom snored. 5 of these 8 snorers had ST segment depression, suggestive of ischaemic heart disease, during apnoeic episodes whereas only 2 had mild dyspneoa and chest pains but they never had ischaemic heart disease. In heavy snorers obstructive sleep apnoea may result in hypoxaemia, hypercapnia, hypoventilation, and acidosis,7,8 leading to pulmonary and systemic hypertension and myocardial depression, which may result in arrhythmias, angina, and dyspnoea. 6However, these changes are mainly due to metabolic changes during obstructive sleep apnoea rather than true angina pectoris. It is premature to claim that snoring is a risk factor for angina pectoris. Department of Cardiology, University Hospital of Wales, Cardiff
V. G. TIRLAPUR*
"Present address Harrow Health Care Centre, Harrow, Middx HA1 4LF. 1.
Lugaresi E, Coccagnia G, Ciragnotta F. Snoring and its clinical implication. In: Guilleminault C, Dement W, Alan R, eds. Sleep apnoea syndromes. New York: Alan R. Liss, 1978: 13-21.
Lugaresi E, Coccagnia G, Farneti P, Montovani M, Cirignotta F. Snoring Electroencephalogr Clin Neurophysiol 1975; 39: 59-64 3. Lugaresi E, Cirgnotta F, Coccagnia G, Piana C. Some epidemiological data on snoring and cardiocirculatory disturbances Sleep 1980; 3: 221-24. 4. Larsson B, Bjontrap P, Tibblin G. The health consequences of moderate obesity. Int J Obesity 1981; 5: 97-101 5. Rimm AA, Werner LH, Van Yserloo B, Bernstein RA. Relation of obesity and disease in 73 532 weight conscious women Public Health Rep 1975, 90: 44-51 6 Yasue H Pathophysiology and treatment of coronary arterial spasm. Chest 1980; 78: 2
216-23. 7.
Mir MA. Daytime drowsiness. Lancet 1982; i: 163-64. AG, Guilleminault C, Schroeder JS, Lehrman KL, Simmons FB, Dement WC. Hemodynamics in sleep induced apnea, studies during wakefulness and sleep. Ann Intern Med 1976; 85: 714-19. Tirlapur VG, Mir MA. Electrocardiographic changes and sleep apnoea syndrome. Lancet 1984, i: 513-14.
Tirlapur VG,
8. Tilkian
9
(CALCULATED
1
AS IN REF
1
Msp I
2)
1
chromosome 11. On the other hand this RFLP explains 0 - 4% or less of the variability in weight and height. These results are similar to those reported for the role of apo-E polymorphisms.4,5 However, unlike the apo-E polymorphism, the Msp I RFLP does not represent allelic variation of the gene product itself. Whether theMsp I RFLP is in linkage disequilibrium with DNA sequences directly involved with apo-AII regulation or whether it defines one of several "loci" having moderate direct effects are issues yet to be resolved. on
Center for
Demographic and Population Genetics,
Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas 77030, USA
CRAIG L. HANIS RANAJIT CHAKRABORTY DAVID HEWETT-EMMETT
1. Falconer DS. Quantitative genetics. New York: Ronald 2. Daiger SP, Miller M, Chakraborty R. Heritability of
Press, 1960.
quantitative variation at the Genet 1984; 36: 663-76. 3. Boerwinkle E. The use of measured genotype information in the genetic analysis of quantitative phenotypes. PhD dissertation, University of Michigan, 1985. 4. Sing CF, Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 1985; 37: 268-85. 5. Robertson FW, Cumming AM. Effects of apoprotein E polymorphism on serum lipoprotein concentration. Arteriosclerosis 1985; 5: 283-92. group-specific component (Gc) locus. Am J Hum
SICK SINUS SYNDROME AND ADENOSINE
SIR,-Dr Dighton (May 18, p 1157), commenting on my hypothesis about a role for adenosine in the sick sinus syndrome (SSS) (April 6, p 786), recognises that the abnormality in sinoatrial node function persists after "complete" vagal and sympathetic block. Therefore autonomic influences, which he seems to consider important, are unlikely to be an essential factor in the pathophysiology of the syndrome. Because these influences are probably peripheral I cited only one reference in relation to the possible effects of adenosine on cardiac autonomic nerves. Dighton asks how adenosine relates to the possibly increased effects of autonomic manoeuvres in SSS patients. However, responses to forced inspiration and exercise were said not to differ between controls and patients in his own studies,I,2 and carotid sinus hypersensitivity is a disease entity distinct from SSS.3The Valsalva manoeuvre may produce slightly different effectsl,2 in patients with the syndrome but this may simply reflect the effects of increased vagal tone on a node already affected by the fundamental pathophysiological processes in the syndrome, whether or not they are adenosine mediated. Adenosine could perhaps account for any enhanced vagal responses if its effect of post-junctional enhancement4of responses to acetylcholine were greater in patients with the SSS than its effect of pre-junctional inhibition. However, abnormalities of sinoatrial function persist in the presence of autonomic blockade, so any effect of adenosine on acetylcholine would be peripheral to the "intrinsic" abnormality of sinoatrial function. Dighton’s statement that he found responses to prostigmine to be greatly reduced in patients with sinoatrial disease contradicts his own comparisons of patients and controls ("differences between the drop in atrial rate and the rate of change of atrial rate fail to reach significant levels",and "no significant difference could be shown between the group with sinoatrial block and the controls"2). This discrepancy seriously undermines the possible relevance of the related comments in his letter. Dighton asks for histochemical evidence for the adenosine5 hypothesis. The in-vivo half-life of adenosine is a few second. Cardiac ischaemia causes adenosine release,and a similar release might occur post mortem so cardiac adenosine concentrations post
be related to the in-vivo situation in patients with SSS. Sinoatrial node biopsy would be unethical. Dighton suggests a role for cholinesterase and, by implication, acetylcholine in ischaemic nodal block. Aminophylline does not affect atrioventricular block produced by acetylcholine, but does antagonise block produced by adenosine or ischaemia.7 Thus adenosine would seem to be a stronger candidate as a possible mediator of ischaemic nodal block than acetylcholine. In his fourth paragraph Dighton asks for the adenosine hypothesis to explain observations unrelated to the heart in SSS. This seems unreasonable.
mortem cannot
Department of Pharmacology and Therapeutics, College of Medicine, University of Wales, Heath Park, CardiffCF4 4XN 1. 2. 3.
ANDREW H. WATT
Dighton DH. Sinus bradycardia: Autonomic influences and clinical assessment. Br Heart J 1974; 36: 791-97. Dighton DH. Sinoatrial block: Autonomic influences and clinical assessment. Br Heart J 1975; 37: 321-25. Zipes DP. Specific arrhythmias: Diagnosis and treatment. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. Philadelphia: WB Saunders, 1984:
683-743. 4. Gustaffson L. Influence of adenosine on responses to vagal nerve stimulation in the anaesthetised rabbit. Acta Physiol Scand 1981, 111: 263-68. 5. Klabunde RE. Dipyridamole inhibition of adenosine metabolism in human blood. Eur J Pharmacol 1983; 93: 21-26. 6. Fox AC, Reed GE, Kaltman AJ, Silk BB. Release of adenosine from human hearts during angina induced by rapid atrial pacing. J Clin Invest 1974; 53: 1447-57. 7. Belardinelli L, Belloni FL, Rubio R, Berne RM. Atrioventricular conduction disturbances during hypoxia: possible role of adenosine in rabbit and guinea pig heart. Circ Res 1980; 47: 684-91.
SNORING AS RISK FACTOR FOR HYPERTENSION AND ANGINA
SIR,-Dr Koskenvuo and colleagues (April 20, p 893) record an association between snoring, hypertension, and angina pectoris. Snoring is three times more common in the obese than in the nonobese,l which is consistent with the finding that obstructive sleep apnoea
syndrome is more common in the obese!-3 and excess body
weight and blood pressure are also related4 5-in short, snoring, obesity, hypertension, ischaemic episodes, and obstructive sleep apnoea are all interrelated.4-6 However, I doubt if snoring is a risk factor for angina. We have done sleep studies in 32 patients with morbid obesity and noted obstructive sleep apnoea in 12,88 ofwhom snored. 5 of these 8 snorers had ST segment depression, suggestive of ischaemic heart disease, during apnoeic episodes whereas only 2 had mild dyspneoa and chest pains but they never had ischaemic heart disease. In heavy snorers obstructive sleep apnoea may result in hypoxaemia, hypercapnia, hypoventilation, and acidosis,7,8 leading to pulmonary and systemic hypertension and myocardial depression, which may result in arrhythmias, angina, and dyspnoea. 6However, these changes are mainly due to metabolic changes during obstructive sleep apnoea rather than true angina pectoris. It is premature to claim that snoring is a risk factor for angina pectoris. Department of Cardiology, University Hospital of Wales, Cardiff
V. G. TIRLAPUR*
"Present address Harrow Health Care Centre, Harrow, Middx HA1 4LF. 1.
Lugaresi E, Coccagnia G, Ciragnotta F. Snoring and its clinical implication. In: Guilleminault C, Dement W, Alan R, eds. Sleep apnoea syndromes. New York: Alan R. Liss, 1978: 13-21.
Lugaresi E, Coccagnia G, Farneti P, Montovani M, Cirignotta F. Snoring Electroencephalogr Clin Neurophysiol 1975; 39: 59-64 3. Lugaresi E, Cirgnotta F, Coccagnia G, Piana C. Some epidemiological data on snoring and cardiocirculatory disturbances Sleep 1980; 3: 221-24. 4. Larsson B, Bjontrap P, Tibblin G. The health consequences of moderate obesity. Int J Obesity 1981; 5: 97-101 5. Rimm AA, Werner LH, Van Yserloo B, Bernstein RA. Relation of obesity and disease in 73 532 weight conscious women Public Health Rep 1975, 90: 44-51 6 Yasue H Pathophysiology and treatment of coronary arterial spasm. Chest 1980; 78: 2
216-23. 7.
Mir MA. Daytime drowsiness. Lancet 1982; i: 163-64. AG, Guilleminault C, Schroeder JS, Lehrman KL, Simmons FB, Dement WC. Hemodynamics in sleep induced apnea, studies during wakefulness and sleep. Ann Intern Med 1976; 85: 714-19. Tirlapur VG, Mir MA. Electrocardiographic changes and sleep apnoea syndrome. Lancet 1984, i: 513-14.
Tirlapur VG,
8. Tilkian
9