- Email: [email protected]
HOW MUCH OF VARIABILITY IN APOLIPOPROTEIN AII CONCENTRATIONS IS EXPLAINED BY POLYMORPHISM ADJACENT TO APO-AII GENE?
1339
Comparison
between
semiquantitative
microalbutest and RIA for
Coronary scores (shaded columns)
and apo-AIi levels (open columns).
microalbuminuria.
0 = observer A; A = observer B; bars indicate SEM; figures in parentheses of samples tested.
indicate number
the microalbutest, defined as the estimates divided by the sum of unacceptable overestimates and correct negative estimates, was 91%. Sensitivity, defined as the number of correct positive results divided by the sum of unacceptable underestimates and correct positive estimates, was 87%.4No interference was found between the variables detected on the N-multistix strips and the accuracy of the microalbutest readings. This rapid bedside reagent seems to be accurate enough for routine patient screening in a diabetic unit. With the reference colour chart, and especially in the clinically significant zone, the observer can interpolate readings satisfactorily. This test may prove to be a useful advance in the epidemiological study of diabetic nephropathy and in the early detection of patients at risk for late
(p>0
5).
The
number of
specificity of negative
correct
Thus between four groups of patients who differed significantly in respect of the extent of CAD, apo-AII concentrations did not differ significantly (see figure). No significant correlation was detected between coronary score and plasma concentration of apo-AII either. We conclude that plasma concentration of apo-AII is not primarily related to CAD or, therefore, to atherosclerosis. Department of Internal Medicine, University of Innsbruck, A-6020 Innsbruck, Austria
CH. BREIER V. MÜHLBERGER E. KNAPP
H. DREXEL H.-J. LISCH H. BRAUNSTEINER
M. Röntgenanatomie und Nomenklatur, Quantifizierung und Dokumentation koronarangiographischer Befunde. In: Kaltenbach M, Roskamm H eds. Vom Belastungs-EKG zur Koronarangiographie. Berlin: Springer V, 1980. 2. Breir C, Mühlberger V, Drexel H, et al. Essential role of post-heparin lipoprotein lipase activity and of plasma testosterone in coronary artery disease. Lancet 1985; i: 1242-44. 1. Kaltenbach
complications. G. SLAMA
Department of Diabetes, Hôtel-Dieu Hospital, 75181
Paris, France
J. BOILLOT N. DESPLANQUE M. LETANOUX
1. Viberti JC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1982; i: 1430-32. 2. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984; 310: 357-60. 3. Keen H, Chlouverakis C. An immunoassay method for urinary albumin at low concentrations. Lancet 1963; ii: 913-14. 4. Armitage P. Statistical methods in medical research. Oxford: Blackwell, 1971.
APOLIPOPROTEIN AII AND CORONARY ARTERY DISEASE
SIR,-Dr Scott and colleagues (April 6, p 771) describe a common DNA polymorphism adjacent to the apoprotein-AII (apo-AII) gene. Homozygosity for this polymorphism in 8 men was associated with a significant increase in serum apo-AII levels, and Scott et al speculated that high apo-AII concentrations in homozygous patients might protect against atherosclerosis. The clinical relevance of this increase in apo-AII concentration remains uncertain and further studies are in progress. As part of a different study on men with angiographically assessed coronary artery disease (CAD)I we measured plasma apo-AII concentrations by endpoint radial immunodiffusion on agarose plates (Immuno, Vienna). The precipitation rings were measured optically with an Immunoviewer to a precision of 0 -1 mm. The extent of CAD was expressed as a coronary score2 after evaluation of coronary cine-
arteriograms. Coronary scores ranged from zero (angiographically normal coronary arteries) to 77, a score over 50 indicating severe occlusion. 19 patients had angiographically normal coronary arteries and the
slight (11), intermediate (31), or severe (28) CAD. apo-AII concentrations (mg/dl plasma) were 42 - 6±2 ° 0, 39-1+2-0, 38-2+1-5, and 41-7±1-5, respectively. rest
had
Mean+SEM
HOW MUCH OF VARIABILITY IN APOLIPOPROTEIN AII CONCENTRATIONS IS EXPLAINED BY POLYMORPHISM ADJACENT TO APO-AII GENE?
SIR,-Dr Scott and colleagues (April 6, p 771) presented data on Msp I restriction fragment length polymorphism (RFLP) in the
an
3’ flanking region of the apolipoprotein All (apo-AII) gene of chromosome 1. They measured concentrations of apo-AII, apo-AI, HDL cholesterol, and triglycerides in three groups of men differing in respect of Msp I site genotype-namely, the two homozygous groups and the heterozygotes-and showed that this common variant significantly affects HDL composition. The significance of these results can be enhanced by applying quantitative genetic techniques which allow the discrete polymorphic variability at a restriction site to be related to the variability in concentrations in the general population-ie, we can estimate the proportion of the variability in, say, apo-AII levels that is attributable to the
polymorphic variability. Of 87 men, 62 were homozygous for a 3 - 0 kb fragment, 8 were homozygous for a 3’77 kb fragment, and 17 were heterozygous. These numbers yield an estimate of the Hardy-Weinberg gene frequency in the population of 0-810 for the common allele. The mean values associated with each genotype and the total variance deduced from the reported standard errors provide the data needed to work out the proportion of the total variability that is ascribable to additive and dominant genetic variability associated with the restriction site. 1-4 Because there were no significant differences in age, weight, or height across genotypes we assumed that no adjustments were required, although there is some age structure in the data. 7 - 2% of the population variability in apo-AII concentration can be explained by variability in this RFLP (see table). This is striking, given the fact that the Msp I site lies in the 3’ flanking region of the apo-AII gene. It would only take a few such loci to account for most of the variation in apo-AII concentration. To a lesser degree, this RFLP also contributes to the variation in the other measures-for example, it explains nearly 3% of apo-AI variation, this gene being
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
Comparison
between
semiquantitative
microalbutest and RIA for
Coronary scores (shaded columns)
and apo-AIi levels (open columns).
microalbuminuria.
0 = observer A; A = observer B; bars indicate SEM; figures in parentheses of samples tested.
indicate number
the microalbutest, defined as the estimates divided by the sum of unacceptable overestimates and correct negative estimates, was 91%. Sensitivity, defined as the number of correct positive results divided by the sum of unacceptable underestimates and correct positive estimates, was 87%.4No interference was found between the variables detected on the N-multistix strips and the accuracy of the microalbutest readings. This rapid bedside reagent seems to be accurate enough for routine patient screening in a diabetic unit. With the reference colour chart, and especially in the clinically significant zone, the observer can interpolate readings satisfactorily. This test may prove to be a useful advance in the epidemiological study of diabetic nephropathy and in the early detection of patients at risk for late
(p>0
5).
The
number of
specificity of negative
correct
Thus between four groups of patients who differed significantly in respect of the extent of CAD, apo-AII concentrations did not differ significantly (see figure). No significant correlation was detected between coronary score and plasma concentration of apo-AII either. We conclude that plasma concentration of apo-AII is not primarily related to CAD or, therefore, to atherosclerosis. Department of Internal Medicine, University of Innsbruck, A-6020 Innsbruck, Austria
CH. BREIER V. MÜHLBERGER E. KNAPP
H. DREXEL H.-J. LISCH H. BRAUNSTEINER
M. Röntgenanatomie und Nomenklatur, Quantifizierung und Dokumentation koronarangiographischer Befunde. In: Kaltenbach M, Roskamm H eds. Vom Belastungs-EKG zur Koronarangiographie. Berlin: Springer V, 1980. 2. Breir C, Mühlberger V, Drexel H, et al. Essential role of post-heparin lipoprotein lipase activity and of plasma testosterone in coronary artery disease. Lancet 1985; i: 1242-44. 1. Kaltenbach
complications. G. SLAMA
Department of Diabetes, Hôtel-Dieu Hospital, 75181
Paris, France
J. BOILLOT N. DESPLANQUE M. LETANOUX
1. Viberti JC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1982; i: 1430-32. 2. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984; 310: 357-60. 3. Keen H, Chlouverakis C. An immunoassay method for urinary albumin at low concentrations. Lancet 1963; ii: 913-14. 4. Armitage P. Statistical methods in medical research. Oxford: Blackwell, 1971.
APOLIPOPROTEIN AII AND CORONARY ARTERY DISEASE
SIR,-Dr Scott and colleagues (April 6, p 771) describe a common DNA polymorphism adjacent to the apoprotein-AII (apo-AII) gene. Homozygosity for this polymorphism in 8 men was associated with a significant increase in serum apo-AII levels, and Scott et al speculated that high apo-AII concentrations in homozygous patients might protect against atherosclerosis. The clinical relevance of this increase in apo-AII concentration remains uncertain and further studies are in progress. As part of a different study on men with angiographically assessed coronary artery disease (CAD)I we measured plasma apo-AII concentrations by endpoint radial immunodiffusion on agarose plates (Immuno, Vienna). The precipitation rings were measured optically with an Immunoviewer to a precision of 0 -1 mm. The extent of CAD was expressed as a coronary score2 after evaluation of coronary cine-
arteriograms. Coronary scores ranged from zero (angiographically normal coronary arteries) to 77, a score over 50 indicating severe occlusion. 19 patients had angiographically normal coronary arteries and the
slight (11), intermediate (31), or severe (28) CAD. apo-AII concentrations (mg/dl plasma) were 42 - 6±2 ° 0, 39-1+2-0, 38-2+1-5, and 41-7±1-5, respectively. rest
had
Mean+SEM
HOW MUCH OF VARIABILITY IN APOLIPOPROTEIN AII CONCENTRATIONS IS EXPLAINED BY POLYMORPHISM ADJACENT TO APO-AII GENE?
SIR,-Dr Scott and colleagues (April 6, p 771) presented data on Msp I restriction fragment length polymorphism (RFLP) in the
an
3’ flanking region of the apolipoprotein All (apo-AII) gene of chromosome 1. They measured concentrations of apo-AII, apo-AI, HDL cholesterol, and triglycerides in three groups of men differing in respect of Msp I site genotype-namely, the two homozygous groups and the heterozygotes-and showed that this common variant significantly affects HDL composition. The significance of these results can be enhanced by applying quantitative genetic techniques which allow the discrete polymorphic variability at a restriction site to be related to the variability in concentrations in the general population-ie, we can estimate the proportion of the variability in, say, apo-AII levels that is attributable to the
polymorphic variability. Of 87 men, 62 were homozygous for a 3 - 0 kb fragment, 8 were homozygous for a 3’77 kb fragment, and 17 were heterozygous. These numbers yield an estimate of the Hardy-Weinberg gene frequency in the population of 0-810 for the common allele. The mean values associated with each genotype and the total variance deduced from the reported standard errors provide the data needed to work out the proportion of the total variability that is ascribable to additive and dominant genetic variability associated with the restriction site. 1-4 Because there were no significant differences in age, weight, or height across genotypes we assumed that no adjustments were required, although there is some age structure in the data. 7 - 2% of the population variability in apo-AII concentration can be explained by variability in this RFLP (see table). This is striking, given the fact that the Msp I site lies in the 3’ flanking region of the apo-AII gene. It would only take a few such loci to account for most of the variation in apo-AII concentration. To a lesser degree, this RFLP also contributes to the variation in the other measures-for example, it explains nearly 3% of apo-AI variation, this gene being
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