- Email: [email protected]
The Fracture Intervention Trial
THE LANCET
Is detrusor instability a prematurely activated (but otherwise normal) micturition reflex? SIR—Malone-Lee’s Nov 23 (p 1395) commentary1 raises not only issues of discrepant analysis 2 in detrusor instability, but also concerns about the gold standard itself: a 70% falsepositive rate of detrusor instability with ambulatory urodynamics.3 He does not say that the same group of symptomfree volunteers had an 18% falsepositive rate3 of detrusor instability with conventional urodynamics, and discounts the practice of ambulatory urodynamics itself. The implication is that conventional urodynamics is valid, and ambulatory urodynamics is not. In fact, both measure the same thing—an abnormal rise in detrusor pressure. 115 patients who gave a history of urge incontinence (wetting before arrival at the lavatory associated with urgency) were given a closely monitored provocative handwashing test.4 The sequence of observed events was, generally speaking, what one would find during normal micturition: a feeling of urgency within a few seconds of start of handwashing, followed by a fall in urethral pressure, then a rise in detrusor pressure, and loss of urine. The results are consistent with the notion that detrusor instability may be the second (urodynamic) limb of a prematurely activated micturition reflex, the first-limb being fall in urethral pressure. On this basis, a simple handwashing test provides several easily accessible indices for discrepant analysis of detrusor instability. are also Khullar’s findings 5 consistent with detrusor instability being a premature activation of the micturition reflex. In such patients,5 the bladder’s stretch receptors fire off prematurely, which is expressed clinically as urgency and frequency. Voluntary contraction of the pelvic floor is known to inhibit urge symptoms. Detrusor pressure is proportional to urethral resistance, and, in turn, inversely to the fourth power of the radius. If voluntary contraction, say, halves the urethral radius, urethral resistance increases by a factor of 16. In patients with urgency and frequency, such massive increases in urethral resistance occur during attempts to counteract an already prematurely contracting bladder; this would cause significant hypertrophy of the urethral striated muscle and the detrusor smooth muscle.5 The finding of detrusor instability in 70% of healthy patients 3 is consistent with what one would expect in a normal
Vol 349 • February 15, 1997
micturition cycle. As the bladder fills, the micturition reflex is activated. If it is inconvenient to empty the bladder, the pelvic floor contracts to assist retention of urine, which increases the urethral resistance and registers urodynamically as a detrusor contraction. Interpreting detrusor instability as being mainly a prematurely activated (but otherwise normal) micturition reflex,4 seems to avoid many of the logical inconsistencies associated with its use as a gold standard pathogenic index. *Pepapa Petros, U Ulmsten Department of Obstetrics and Gynaecology, University of Uppsala, Academic Hospital, S751 85 Uppsala, Sweden
1
2 3
4
5
Malone-Lee J. Is detrusor instability and hypertrophy a smooth-muscle disease of the lower urinary tract. Lancet 1996; 348: 1395. Hadgu A. The discrepancy in discrepant analysis. Lancet 1966; 348: 592–93. van Doom, van Waalwijk ESC, Remmers A, Jaknegt RA. Conventional and extramural ambulatory urodynamic testing of the lower urinary tract in the female. J Urol 1992; 147: 1319–25. Petros PE, Ulmsten U. Bladder instability in women: a premature activation of the micturition reflex. Neurourol Urod 1993; 12: 235–39. Khullar V, Cardozo LD, Salvatore S, Hill S. Ultrasound: a noninvasive screening test for detrusor instability. Br J Obstet Gynaecol 1996; 103: 904–08.
results and quality control. 2 There can be no denying the importance of this clinical area and the need to consider appropriate preventive measures, although there may be several therapeutic options that merit further research. 3 Unfortunately the evidence for taking decisions about how best to prevent serious bone fracture in the elderly is thin, a position perhaps similar to that for the secondary prevention of ischaemic heart disease in the 1970s. Perhaps it is time to repeat the plea for trials which address clinically relevant situations4 but which are also mindful of economic reality. Adrian Phillips Department of Public Health Medicine, Walsall Health Authority, Walsall WS1 1TE, UK
1
2
3
4
Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996; 348: 1535–41. Effective Health Care. Screening for osteoporosis to prevent fractures, Vol 1 (1). Leeds: School of Public Health, University of Leeds, 1992. Effective Health Care. Preventing falls and subsequent injury in older people, Vol 2 (4). Leeds: School of Public Health, University of Leeds, 1996. Yusuf S, Collins R, Peto R. Why do we need some large, simple randomized trials? Stat Med 1984; 3: 409–20.
The Fracture Intervention Trial
Authors’ reply
SIR—The Fracture Intervention Trial (FIT) Research Group (Dec 7, p 1535)1 attempt to address one aspect of a major public health problem in the developed world—namely, osteoporosis-related serious bone fracture—but I have several concerns about the clinical relevance of this trial. The FIT trial showed a 50% reduction in relative risk for hip fracture, the most clinically important endpoint, but only a 1·1% reduction in absolute risk; this means that 300 patients would need to be treated for 1 year to prevent one hip fracture. With available prices this equates to the cost of avoiding one hip fracture to be about £100 000 (US $162 000). There are issues relating to the possible implementation of this trial in the general clinical setting. Few people with trabecular bone fracture are diagnosed as having osteoporosis before this unfortunate event, very different to the entry criteria for FIT. Furthermore, bone densitometry and related measurements do not enjoy the widespread agreement observed for other biological indices. There is still considerable uncertainty about the relation between particular values and risk, as well as the reproducibility of
SIR—The FIT trial has as its primary endpoint clinically evident fracture. Use of a fracture endpoint, rather than the surrogate endpoint of bone mineral density which has been used in many previous trials in this area, provides the data necessary to estimate the most cost-effective use of alendronate. Phillips’ casual estimate of the reduction of one hip fracture associated with 300 person years of alendronate use is incomplete since such use would also result in the prevention of 16 vertebral fractures in seven women, as well as two wrist fractures. A careful analysis is required to compare the sum of the reductions and the consequent impacts on quality of life against the costs of this therapy over short periods (eg, 3–5 years) as well as longer periods. Such analyses are being carried out by various groups around the world including the National Osteoporosis Foundation in the USA. The arm of FIT reported in The Lancet includes women with low bone mass and existing vertebral fractures. It has been estimated that about 20% of white women over age 65 have such fractures.1,2 A second arm of FIT conducted in 4432 women with low bone mass but who did not have
505
THE LANCET
Occupation
First coronary event
Coronary death
Non-adjusted
Age-adjusted
Multifactorial adjusted*
Non-adjusted
Age-adjusted
Multifactorial adjusted*
Men White collar† Blue collar Farmer
1·00 1·17 (0·97–1·42)† 1·42 (1·18–1·72)
1·00 1·16 (0·95–1·40) 1·00 (0·82–1·20)
1·00 1·05 (0·87–1·27) 0·87 (0·72–1·06)
1·00 1·10 (0·81–1·48) 1·48 (1·11–1–96)
1·00 1·08 (0·80–1·46) 0·99 (0·74–1·33)
1·00 0·97 (0·72–1·32) 0·86 (0·65–1·16)
Women White collar† Blue collar Farmer
1·00 1·17 (0·76–1·82) 1·56 (1·18–2·05)
1·00 1·26 (0·81–1·95) 1·11 (0·84–1·46)
1·00 1·20 (0·77–1·86) 1·07 (0·81–1·42)
1·00 1·06 (0·41–2·70) 2·68 (1·66–4·33)
1·00 1·22 (0·48–3·11) 1·84 (1·14–2·97)
1·00 1·09 (0·43–2·80) 1·67 (1·03–2·75)
*Age, smoking, serum cholesterol, systolic blood pressure; †reference group.
Risk ratios (95% CI) for first coronary event and coronary death by occupation among 7660 men and 8421 women in eastern Finland
vertebral fractures at baseline will be completed in 1997. Since fracture risk increases with decreasing bone density in a continuous manner,3 any cut point for defining disease is arbitrary. However, the bone density criterion chosen for inclusion into both arms of FIT was similar to current definitions proposed by the World Health Organization.4 In the USA alone, it is estimated that about 7–10 million white women meet this definition.5 Evidence suggests that predictive value of bone density for fracture risk is at least as good as other measurements such as lipids or blood pressure for prediction of heart disease. Furthermore, techniques for assessment of bone density are at least as reproducible as lipid concentrations and blood pressure, both in terms of measurement error and true biological variability. There can be no denying the need for more widely applicable diagnostic and preventative strategies in osteoporosis. Nonetheless, we believe that the FIT results represent an important step forward in showing that among older women with established osteoporosis, treatment can reduce the incidence of fractures, including the devastating consequences of hip fractures. *Dennis M Black, Steve R Cummings, for the Fracture Intervention Trial Research Group *Department of Epidemiology and Biostatistics, and Division of General Internal Medicine, University of California, San Francisco, California 94143, USA
1
2
3
4
Melton LJ, Kan SH, Frye MA, Wahner HW, O’Fallon WM, Riggs BL. Epidemiology of vertebral fractures in women. Am J Epidemiol 1989; 129: 1000–11. Black DM, Palermo L, Nevitt MC, et al. Comparison of methods for defining prevalent vertebral deformities: the study of osteoporotic fractures. J Bone Miner Res 1995; 10: 890–902. Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for prediction of hip fractures. Lancet 1993; 341: 72–75. Kanis JA, Who Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. Osteoporosis Int 1994; 4:
506
5
368–81. Looker AC, Wahner HW, Dunn WL, et al. Proximal femur bone mineral levels of US adults. Osteoporisis Int 1995; 5: 389–409.
Occupation, fibrinogen, and heart disease SIR—Although fibrinogen may be a mediator in chronic infection, inflammation, and coronary disease, as Sjögren suggests (Nov 16, p 1389),1 our data do not support his hypothesis about occupation as a determinant of coronary heart disease. From our crude figures,2 Sjögren estimated higher coronary disease risk among farmers compared with whitecollar workers, but his analysis took no account of age as an important confounding variable. In Finland, the average age of working farmers is higher (about 4 years) compared with people in other professions (about 4 years longer). In our table we present the relative risk of first coronary event and death from coronary disease among farmers, blue-collar workers, and white-collar workers. For both sexes, the crude risk of coronary disease was much higher among farmers than white-collar workers. When age was included as a covariate, this difference in relative risk disappeared among men. Among women farmers the risk ratio of coronary disease also greatly decreased after adjustment for age, but the risk of coronary death still remained higher in farmers than among the other women. Adjustment for smoking, serum total cholesterol, and systolic blood pressure showed further decrease in the risk of coronary disease in farmers, compared with other occupational groups. Fibrinogen levels were not obtained during the baseline surveys of our study cohorts in the 1970s. We have, however, done similar risk-factor surveys since then every 5 years. In the last survey (1992) plasma fibrinogen was revealed in a sub-sample of men and women aged 45–64 years.3 When the values of different occupational groups were compared, the age-
adjusted mean serum fibrinogen concentration in male farmers did not differ from the mean fibrinogen values of male white-collar and blue-collar workers (3·28 [SD 0·68], 3·32 [0·77], and 3·41 [0·73], respectively). In women, plasma fibrinogen was higher among farmers than among white collar and blue collar workers (3·57 [0·82], 3·36 [0·75], and 3·40 [0·67], respectively; farmers vs white-collar workers p=0·049). We should obviously be cautious in comparing our findings in the 1990s to the situation of the 1970s. However, during our baseline surveys women farmers may have been more exposed than women in other professions to factors leading to high serum fibrinogen, and subsequently to increased coronary disease risk. *Pekka Jousilahti, Erkki Vartiainen, Jaakko Tuomilehto, Pekka Puska National Public Health Institute, Department of Epidemiology and Health Promotion, FIN-00300 Helsinki, Finland
1
2
3
Sjögren B. Chronic bronchitis and risk of coronary heart disease. Lancet 1996; 348: 1389. Jousilahti P, Vartiainen E, Tuomilehto J, Puska P. Symptoms of chronic bronchitis and the risk of coronary disease. Lancet 1996; 348: 567–72. Salomaa VV, Rasi VP, Vahtera EM, et al. Haemostatic factors and lipoprotein(a) in three geographical areas in Finland: the Finrisk haemostasis study. J Cardiovascular Risk 1994; 1: 241–48.
Dietary salt and renal stone disease S IR —The valuable Grand Round (Dec 7, p 1561) on renal stones 1 does not mention the possible role of high dietary salt intake in the pathogenesis of this common disease. As Unwin 1 notes hypercalciuria is commonly found in people with nephrolithiasis, and is deemed a pivotal risk factor for stone formation and growth. 2 High urinary sodium is associated with high urinary calcium; high urinary potassium with low urinary calcium. 2
Vol 349 • February 15, 1997
Is detrusor instability a prematurely activated (but otherwise normal) micturition reflex? SIR—Malone-Lee’s Nov 23 (p 1395) commentary1 raises not only issues of discrepant analysis 2 in detrusor instability, but also concerns about the gold standard itself: a 70% falsepositive rate of detrusor instability with ambulatory urodynamics.3 He does not say that the same group of symptomfree volunteers had an 18% falsepositive rate3 of detrusor instability with conventional urodynamics, and discounts the practice of ambulatory urodynamics itself. The implication is that conventional urodynamics is valid, and ambulatory urodynamics is not. In fact, both measure the same thing—an abnormal rise in detrusor pressure. 115 patients who gave a history of urge incontinence (wetting before arrival at the lavatory associated with urgency) were given a closely monitored provocative handwashing test.4 The sequence of observed events was, generally speaking, what one would find during normal micturition: a feeling of urgency within a few seconds of start of handwashing, followed by a fall in urethral pressure, then a rise in detrusor pressure, and loss of urine. The results are consistent with the notion that detrusor instability may be the second (urodynamic) limb of a prematurely activated micturition reflex, the first-limb being fall in urethral pressure. On this basis, a simple handwashing test provides several easily accessible indices for discrepant analysis of detrusor instability. are also Khullar’s findings 5 consistent with detrusor instability being a premature activation of the micturition reflex. In such patients,5 the bladder’s stretch receptors fire off prematurely, which is expressed clinically as urgency and frequency. Voluntary contraction of the pelvic floor is known to inhibit urge symptoms. Detrusor pressure is proportional to urethral resistance, and, in turn, inversely to the fourth power of the radius. If voluntary contraction, say, halves the urethral radius, urethral resistance increases by a factor of 16. In patients with urgency and frequency, such massive increases in urethral resistance occur during attempts to counteract an already prematurely contracting bladder; this would cause significant hypertrophy of the urethral striated muscle and the detrusor smooth muscle.5 The finding of detrusor instability in 70% of healthy patients 3 is consistent with what one would expect in a normal
Vol 349 • February 15, 1997
micturition cycle. As the bladder fills, the micturition reflex is activated. If it is inconvenient to empty the bladder, the pelvic floor contracts to assist retention of urine, which increases the urethral resistance and registers urodynamically as a detrusor contraction. Interpreting detrusor instability as being mainly a prematurely activated (but otherwise normal) micturition reflex,4 seems to avoid many of the logical inconsistencies associated with its use as a gold standard pathogenic index. *Pepapa Petros, U Ulmsten Department of Obstetrics and Gynaecology, University of Uppsala, Academic Hospital, S751 85 Uppsala, Sweden
1
2 3
4
5
Malone-Lee J. Is detrusor instability and hypertrophy a smooth-muscle disease of the lower urinary tract. Lancet 1996; 348: 1395. Hadgu A. The discrepancy in discrepant analysis. Lancet 1966; 348: 592–93. van Doom, van Waalwijk ESC, Remmers A, Jaknegt RA. Conventional and extramural ambulatory urodynamic testing of the lower urinary tract in the female. J Urol 1992; 147: 1319–25. Petros PE, Ulmsten U. Bladder instability in women: a premature activation of the micturition reflex. Neurourol Urod 1993; 12: 235–39. Khullar V, Cardozo LD, Salvatore S, Hill S. Ultrasound: a noninvasive screening test for detrusor instability. Br J Obstet Gynaecol 1996; 103: 904–08.
results and quality control. 2 There can be no denying the importance of this clinical area and the need to consider appropriate preventive measures, although there may be several therapeutic options that merit further research. 3 Unfortunately the evidence for taking decisions about how best to prevent serious bone fracture in the elderly is thin, a position perhaps similar to that for the secondary prevention of ischaemic heart disease in the 1970s. Perhaps it is time to repeat the plea for trials which address clinically relevant situations4 but which are also mindful of economic reality. Adrian Phillips Department of Public Health Medicine, Walsall Health Authority, Walsall WS1 1TE, UK
1
2
3
4
Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996; 348: 1535–41. Effective Health Care. Screening for osteoporosis to prevent fractures, Vol 1 (1). Leeds: School of Public Health, University of Leeds, 1992. Effective Health Care. Preventing falls and subsequent injury in older people, Vol 2 (4). Leeds: School of Public Health, University of Leeds, 1996. Yusuf S, Collins R, Peto R. Why do we need some large, simple randomized trials? Stat Med 1984; 3: 409–20.
The Fracture Intervention Trial
Authors’ reply
SIR—The Fracture Intervention Trial (FIT) Research Group (Dec 7, p 1535)1 attempt to address one aspect of a major public health problem in the developed world—namely, osteoporosis-related serious bone fracture—but I have several concerns about the clinical relevance of this trial. The FIT trial showed a 50% reduction in relative risk for hip fracture, the most clinically important endpoint, but only a 1·1% reduction in absolute risk; this means that 300 patients would need to be treated for 1 year to prevent one hip fracture. With available prices this equates to the cost of avoiding one hip fracture to be about £100 000 (US $162 000). There are issues relating to the possible implementation of this trial in the general clinical setting. Few people with trabecular bone fracture are diagnosed as having osteoporosis before this unfortunate event, very different to the entry criteria for FIT. Furthermore, bone densitometry and related measurements do not enjoy the widespread agreement observed for other biological indices. There is still considerable uncertainty about the relation between particular values and risk, as well as the reproducibility of
SIR—The FIT trial has as its primary endpoint clinically evident fracture. Use of a fracture endpoint, rather than the surrogate endpoint of bone mineral density which has been used in many previous trials in this area, provides the data necessary to estimate the most cost-effective use of alendronate. Phillips’ casual estimate of the reduction of one hip fracture associated with 300 person years of alendronate use is incomplete since such use would also result in the prevention of 16 vertebral fractures in seven women, as well as two wrist fractures. A careful analysis is required to compare the sum of the reductions and the consequent impacts on quality of life against the costs of this therapy over short periods (eg, 3–5 years) as well as longer periods. Such analyses are being carried out by various groups around the world including the National Osteoporosis Foundation in the USA. The arm of FIT reported in The Lancet includes women with low bone mass and existing vertebral fractures. It has been estimated that about 20% of white women over age 65 have such fractures.1,2 A second arm of FIT conducted in 4432 women with low bone mass but who did not have
505
THE LANCET
Occupation
First coronary event
Coronary death
Non-adjusted
Age-adjusted
Multifactorial adjusted*
Non-adjusted
Age-adjusted
Multifactorial adjusted*
Men White collar† Blue collar Farmer
1·00 1·17 (0·97–1·42)† 1·42 (1·18–1·72)
1·00 1·16 (0·95–1·40) 1·00 (0·82–1·20)
1·00 1·05 (0·87–1·27) 0·87 (0·72–1·06)
1·00 1·10 (0·81–1·48) 1·48 (1·11–1–96)
1·00 1·08 (0·80–1·46) 0·99 (0·74–1·33)
1·00 0·97 (0·72–1·32) 0·86 (0·65–1·16)
Women White collar† Blue collar Farmer
1·00 1·17 (0·76–1·82) 1·56 (1·18–2·05)
1·00 1·26 (0·81–1·95) 1·11 (0·84–1·46)
1·00 1·20 (0·77–1·86) 1·07 (0·81–1·42)
1·00 1·06 (0·41–2·70) 2·68 (1·66–4·33)
1·00 1·22 (0·48–3·11) 1·84 (1·14–2·97)
1·00 1·09 (0·43–2·80) 1·67 (1·03–2·75)
*Age, smoking, serum cholesterol, systolic blood pressure; †reference group.
Risk ratios (95% CI) for first coronary event and coronary death by occupation among 7660 men and 8421 women in eastern Finland
vertebral fractures at baseline will be completed in 1997. Since fracture risk increases with decreasing bone density in a continuous manner,3 any cut point for defining disease is arbitrary. However, the bone density criterion chosen for inclusion into both arms of FIT was similar to current definitions proposed by the World Health Organization.4 In the USA alone, it is estimated that about 7–10 million white women meet this definition.5 Evidence suggests that predictive value of bone density for fracture risk is at least as good as other measurements such as lipids or blood pressure for prediction of heart disease. Furthermore, techniques for assessment of bone density are at least as reproducible as lipid concentrations and blood pressure, both in terms of measurement error and true biological variability. There can be no denying the need for more widely applicable diagnostic and preventative strategies in osteoporosis. Nonetheless, we believe that the FIT results represent an important step forward in showing that among older women with established osteoporosis, treatment can reduce the incidence of fractures, including the devastating consequences of hip fractures. *Dennis M Black, Steve R Cummings, for the Fracture Intervention Trial Research Group *Department of Epidemiology and Biostatistics, and Division of General Internal Medicine, University of California, San Francisco, California 94143, USA
1
2
3
4
Melton LJ, Kan SH, Frye MA, Wahner HW, O’Fallon WM, Riggs BL. Epidemiology of vertebral fractures in women. Am J Epidemiol 1989; 129: 1000–11. Black DM, Palermo L, Nevitt MC, et al. Comparison of methods for defining prevalent vertebral deformities: the study of osteoporotic fractures. J Bone Miner Res 1995; 10: 890–902. Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for prediction of hip fractures. Lancet 1993; 341: 72–75. Kanis JA, Who Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. Osteoporosis Int 1994; 4:
506
5
368–81. Looker AC, Wahner HW, Dunn WL, et al. Proximal femur bone mineral levels of US adults. Osteoporisis Int 1995; 5: 389–409.
Occupation, fibrinogen, and heart disease SIR—Although fibrinogen may be a mediator in chronic infection, inflammation, and coronary disease, as Sjögren suggests (Nov 16, p 1389),1 our data do not support his hypothesis about occupation as a determinant of coronary heart disease. From our crude figures,2 Sjögren estimated higher coronary disease risk among farmers compared with whitecollar workers, but his analysis took no account of age as an important confounding variable. In Finland, the average age of working farmers is higher (about 4 years) compared with people in other professions (about 4 years longer). In our table we present the relative risk of first coronary event and death from coronary disease among farmers, blue-collar workers, and white-collar workers. For both sexes, the crude risk of coronary disease was much higher among farmers than white-collar workers. When age was included as a covariate, this difference in relative risk disappeared among men. Among women farmers the risk ratio of coronary disease also greatly decreased after adjustment for age, but the risk of coronary death still remained higher in farmers than among the other women. Adjustment for smoking, serum total cholesterol, and systolic blood pressure showed further decrease in the risk of coronary disease in farmers, compared with other occupational groups. Fibrinogen levels were not obtained during the baseline surveys of our study cohorts in the 1970s. We have, however, done similar risk-factor surveys since then every 5 years. In the last survey (1992) plasma fibrinogen was revealed in a sub-sample of men and women aged 45–64 years.3 When the values of different occupational groups were compared, the age-
adjusted mean serum fibrinogen concentration in male farmers did not differ from the mean fibrinogen values of male white-collar and blue-collar workers (3·28 [SD 0·68], 3·32 [0·77], and 3·41 [0·73], respectively). In women, plasma fibrinogen was higher among farmers than among white collar and blue collar workers (3·57 [0·82], 3·36 [0·75], and 3·40 [0·67], respectively; farmers vs white-collar workers p=0·049). We should obviously be cautious in comparing our findings in the 1990s to the situation of the 1970s. However, during our baseline surveys women farmers may have been more exposed than women in other professions to factors leading to high serum fibrinogen, and subsequently to increased coronary disease risk. *Pekka Jousilahti, Erkki Vartiainen, Jaakko Tuomilehto, Pekka Puska National Public Health Institute, Department of Epidemiology and Health Promotion, FIN-00300 Helsinki, Finland
1
2
3
Sjögren B. Chronic bronchitis and risk of coronary heart disease. Lancet 1996; 348: 1389. Jousilahti P, Vartiainen E, Tuomilehto J, Puska P. Symptoms of chronic bronchitis and the risk of coronary disease. Lancet 1996; 348: 567–72. Salomaa VV, Rasi VP, Vahtera EM, et al. Haemostatic factors and lipoprotein(a) in three geographical areas in Finland: the Finrisk haemostasis study. J Cardiovascular Risk 1994; 1: 241–48.
Dietary salt and renal stone disease S IR —The valuable Grand Round (Dec 7, p 1561) on renal stones 1 does not mention the possible role of high dietary salt intake in the pathogenesis of this common disease. As Unwin 1 notes hypercalciuria is commonly found in people with nephrolithiasis, and is deemed a pivotal risk factor for stone formation and growth. 2 High urinary sodium is associated with high urinary calcium; high urinary potassium with low urinary calcium. 2
Vol 349 • February 15, 1997