A longitudinal study of altered taste and smell perception and change in blood pressure.

BACKGROUND AND AIMS: Previous studies suggest that olfactory receptors, which mediate smell chemosensation, are located in the kidney and involved in blood pressure regulation. Mammalian epithelial sodium channels located in taste receptor cells are also found to participate in blood pressure regulation. However, there is currently no human study that has examined the association between taste and smell function and blood pressure. We thus conducted a longitudinal study to examine whether participants with altered taste and smell perception had larger increases in blood pressure compared with those without altered perception in a community-based cohort. METHODS AND RESULTS: The study included 5190 Chinese adults (4058 men and 1132 women) who were normotensive at baseline. Taste and smell perception were assessed via questionnaire in 2012 (baseline). Blood pressure was measured in 2012 and 2014 to determine relative change in blood pressure. Mean differences of 2-year blood pressure change and 95% confidence intervals (CIs) across four categories of taste and smell perception were calculated after adjusting for known risk factors for hypertension. After adjusting for potential confounders, individuals with altered taste and smell perception had larger increases in systolic blood pressure (adjusted mean difference = 5.1 mmHg, 95% CI: 0.1-10.0, p-value: 0.04) and mean arterial pressure (adjusted mean difference = 3.8 mmHg, 95% CI: 0.4-7.1, p-value: 0.03) after two years of follow-up compared with those having neither altered taste nor altered smell perception. No significant association was observed in individuals with altered taste or smell perception only. CONCLUSION: Our results suggest an association between chemosensory function and blood pressure.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Plasma uric acid concentrations and risk of ischaemic stroke in women.

BACKGROUND AND PURPOSE: Elevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. METHODS: A nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. RESULTS: In matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval (CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. CONCLUSIONS: Plasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk.

Calcium supplement intake and risk of cardiovascular disease in women.

UNLABELLED: Some recent reports suggest that calcium supplement use may increase risk of cardiovascular disease. In a prospective cohort study of 74,245 women in the Nurses' Health Study with 24 years of follow-up, we found no independent associations between supplemental calcium intake and risk of incident coronary heart disease (CHD) and stroke. INTRODUCTION: Some recent reports suggest that calcium supplements may increase cardiovascular disease (CVD) risk. The objective was to examine the independent associations between calcium supplement use and risk of CVD. METHODS: We conducted a prospective cohort study of supplemental calcium use and incident CVD in 74,245 women in the Nurses' Health Study (1984-2008) free of CVD and cancer at baseline. Calcium supplement intake was assessed every 4 years. Outcomes were incident CHD (nonfatal or fatal MI) and stroke (ischemic or hemorrhagic), confirmed by medical record review. RESULTS: During 24 years of follow-up, 4,565 cardiovascular events occurred (2,709 CHD and 1,856 strokes). At baseline, women who took calcium supplements had higher levels of physical activity, smoked less, and had lower trans fat intake compared with those who did not take calcium supplements. After multivariable adjustment for age, body mass index, dietary calcium, vitamin D intake, and other CVD risk factors, the relative risk of CVD for women taking >1,000 mg/day of calcium supplements compared with none was 0.82 (95% confidence interval [CI] 0.74 to 0.92; p for trend <0.001). For women taking >1,000 mg/day of calcium supplements compared with none, the multivariable-adjusted relative risk for CHD was 0.71 (0.61 to 0.83; p for trend < 0.001) and for stroke was 1.03 (0.87 to 1.21; p for trend = 0.61). The relative risks were similar in analyses limited to non-smokers, women without hypertension, and women who had regular physical exams. CONCLUSIONS: Our findings do not support the hypothesis that calcium supplement intake increases CVD risk in women.

Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study.

BACKGROUND: Psoriasis has been linked to cardiovascular comorbidities in cross-sectional studies, but evidence regarding the association between psoriasis and incident cardiovascular disease (CVD) is limited. OBJECTIVES: To make a prospective evaluation of the association between psoriasis and risk of incident nonfatal CVD. METHODS: Participants (n = 96, 008) were included from the Nurses' Health Study II, and followed for 18 years. Information on physician-diagnosed psoriasis was obtained by self-report and diagnosis was confirmed by supplementary questionnaires. We included 2463 individuals with self-reported psoriasis and a subsample of 1242 with validated psoriasis. The main outcome was incident nonfatal CVD events [nonfatal myocardial infarction (MI) and nonfatal stroke], ascertained by biennial questionnaires and confirmed. RESULTS: During 1 709 069 person-years of follow-up, 713 incident nonfatal CVD events were confirmed. Psoriasis was associated with a significantly increased multivariate-adjusted hazard ratio (HR) of nonfatal CVD, 1·55 [95% confidence interval (CI): 1·04-2·31]. HRs for nonfatal MI and stroke were 1·70 (95% CI: 1·01-2·84) and 1·45 (95% CI: 0·80-2·65), respectively. The association remained consistent in a sensitivity analysis of confirmed psoriasis (HR: 2·06, 95% CI: 1·31-3·26). For individuals with concomitant psoriatic arthritis, the risk of nonfatal CVD was even higher (HR: 3·47; 95% CI: 1·85-6·51). Women diagnosed with psoriasis at < 40 years of age or with duration of psoriasis ≥ 9 years had substantial elevations in CVD risk: HR: 3·26 (95% CI: 1·21-8·75) and 3·09 (95% CI: 1·15-8·29), respectively. CONCLUSIONS: Psoriasis is an independent predictor for nonfatal CVD among women, with particularly high risk for those with longer duration of psoriasis and concomitant psoriatic arthritis.

Lipid and inflammatory biomarkers and kidney function decline in type 2 diabetes.

AIMS/HYPOTHESIS: Potentially modifiable biomarkers may influence the decline in estimated GFR (eGFR), but few data are currently available in type 2 diabetic adults. METHODS: We studied 516 women with type 2 diabetes in the Nurses' Health Study with data on lipid and inflammatory biomarkers from plasma collected in 1989 and plasma creatinine in samples collected in 1989 and 2000. An estimated GFR decline of >or=25% over 11 years was the outcome of interest. RESULTS: Comparing the highest with the lowest quartile, soluble tumour necrosis factor receptor 2 (sTNFR-2) was independently associated with an eGFR decline of >or=25% (multivariate OR 5.81; 95% CI 2.90-11.65); this association was stronger in obese women (OR 16.76; 95% CI 4.69-59.90 for BMI >or=30 kg/m(2); OR 2.78, 95% CI 1.12-6.89 for BMI <30 kg/m(2); p for interaction = 0.02). No lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL-cholesterol, triacylglycerols, lipoprotein(a), or apolipoprotein B) or other markers of inflammation (C-reactive protein, fibrinogen, E-selectin, intracellular cell adhesion molecule 1, leptin or adiponectin) were significantly associated with eGFR decline after multivariable adjustment. CONCLUSIONS/INTERPRETATION: Elevated sTNFR-2 levels may be an important and potentially modifiable risk factor for eGFR decline in type 2 diabetes, especially in those with a BMI of >or=30 kg/m(2).

[Current issues in measurement and reporting of urinary albumin excretion]. / Données actuelles sur le dosage de l'excrétion urinaire de l'albumine.

Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement. The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the erro-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences has been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no referance materials for either analyte in urine. The recommanded reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethicity) nor the continuous increase in risk related to albumin excretion. Clinical needs have been identified for standardization of (a) urine collection methodes, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.

24-h uric acid excretion and the risk of kidney stones.

There is uncertainty about the relation between 24-h urinary uric acid excretion and the risk of calcium oxalate nephrolithiasis. In addition, the risk associated with different levels of other urinary factors needs clarification. We performed a cross-sectional study of 24-h urine excretion and the risk of kidney stone formation in 3350 men and women, of whom 2237 had a history of nephrolithiasis. After adjusting for other urinary factors, urinary uric acid had a significant inverse association with stone formation in men, a marginal inverse association with risk in younger women, and no association in older women. The risk of stone formation in men and women significantly rose with increasing urine calcium and oxalate, and significantly decreased with increasing citrate and urine volume, with the change in risk beginning below the traditional normal thresholds. Other urinary factors were also associated with risk, but this varied by age and gender. Our study does not support the prevailing belief that higher urine uric acid excretion increases the risk for calcium oxalate stone formation. In addition, the current definitions of normal levels for urinary factors need to be re-evaluated.

A prospective study of age and lifestyle factors in relation to community-acquired pneumonia in US men and women.

BACKGROUND: Information is limited on risk factors for community-acquired pneumonia (CAP) in free-living populations. We examined the associations of age, smoking status, body mass index (BMI), weight change during adulthood, physical activity, and alcohol intake with risk of CAP among men and women. METHODS: The study population included 26,429 men aged 44 to 79 years from the Health Professionals Follow-up Study and 78,062 women aged 27 to 44 years from the Nurses' Health Study II. Information was collected by biennial mailed questionnaires and the main outcome was physician-diagnosed incident pneumonia. RESULTS: There were 290 cases among men (6 years of follow-up) and 305 cases among women (2 years of follow-up). Age, smoking status, BMI, physical activity, and alcohol intake were taken into account in the multivariate logistic regression model. There was a dose-response relation between aging and risk of CAP among men. Compared with never smokers, current smoking was associated with risk of CAP among men (relative risk, 1.46; 95% confidence interval, 1.00-2.14) and women (relative risk, 1.55; 95% confidence interval, 1.15-2.10). In addition, BMI was directly associated with an increased risk of CAP among women. Compared with the participants who maintained their weight during adulthood, the risks were nearly 2-fold higher among men and women who gained 40 lb or more (> or =18 kg). The risk of CAP decreased with increasing physical activity among women. We also found no significant relation between alcohol intake and risk of CAP among men and women. CONCLUSIONS: Smoking and excessive weight gain are risk factors for CAP among men and women, and physical activity was inversely associated with risk of CAP only among women. The incidence of CAP could possibly be decreased by lifestyle factors.

Diabetes, hemoglobin A(1c), cholesterol, and the risk of moderate chronic renal insufficiency in an ambulatory population.

Moderate chronic renal insufficiency is common, with 12.5 million individuals in the United States estimated to have a creatinine clearance less than 50 mL/min/1.73 m(2). Little is known about the risk factors for moderate chronic renal insufficiency. We studied 1, 428 subjects with Cockcroft-Gault-estimated creatinine clearances greater than 70 mL/min in a hospital-based ambulatory population. Over a mean of 5.7 +/- 1.3 years, 86 subjects developed moderate chronic renal insufficiency, defined as a decrease in creatinine clearance to less than 60 mL/min (1.1 case/100 person-years). Risk factors for moderate chronic renal insufficiency were identified using a proportional hazards model controlling for age, sex, race, systolic blood pressure, and angiotensin-converting enzyme (ACE) inhibitor use. The risk for developing moderate chronic renal insufficiency was associated with diabetes mellitus (relative risk, 2.1; 95% confidence interval [CI], 1.3 to 3.3) and elevated hemoglobin A(1c) levels. Compared with subjects with normoglycemia (hemoglobin A(1c) 9.0%) was 2.7 (95% CI, 1.4 to 5.1). The development of moderate chronic renal insufficiency was also independently predicted by elevated maximum serum cholesterol level. Compared with subjects with maximum cholesterol levels of 250 mg/dL or less, the relative risk for those with maximum cholesterol levels greater than 350 mg/dL was 2.4 (95% CI, 1.1 to 5.2). Similar relative risks were obtained when moderate chronic renal insufficiency was defined by the development of an increase in serum creatinine level. Hypercholesterolemia was also associated with moderate chronic renal insufficiency among persons without diabetes. In conclusion, the risk for developing moderate chronic renal insufficiency is increased by diabetes and elevated hemoglobin A(1c) and serum cholesterol levels. Modification of these risk factors may decrease the incidence of moderate chronic renal insufficiency.

Nephrolithiasis and risk of hypertension in women.

Cross-sectional and prospective studies of men suggest a positive association between nephrolithiasis and hypertension. However, this association remains controversial in women. We conducted a prospective study of the relation between nephrolithiasis and the risk for hypertension in the Nurses' Health Study, a cohort of 89,376 women aged 34 to 59 years in 1980. Information on the history of nephrolithiasis, physician-diagnosed hypertension, and other relevant exposures was obtained by biennial mailed questionnaire. A history of nephrolithiasis before 1980 was reported by 2,558 women (2.9%), and a history of hypertension was reported by 11,883 women (13.3%). Among women without hypertension before 1980, 12,540 women reported a new diagnosis of hypertension between 1980 and 1992, during 711,039 person-years of follow-up. Compared with those without a history of nephrolithiasis, the age-adjusted relative risk (RR) for incident hypertension in women with such a history was 1.36 (95% confidence interval [CI], 1.20 to 1.43). After further adjustment for body mass index (BMI) and the intake of calcium, sodium, potassium, magnesium, caffeine, and alcohol, the RR was only slightly attenuated (RR=1.24; 95% CI, 1.13 to 1.37). In contrast, the occurrence of incident nephrolithiasis during follow-up was similar in women with hypertension at baseline compared with women without (adjusted odds ratio [OR]=1.01; 95% CI, 0.85 to 1.20). These data are consistent with the results obtained in men and support the hypothesis that a history of nephrolithiasis is associated with an increased risk for subsequent hypertension. Dietary factors, such as the intake of calcium, sodium, and potassium, do not explain this association. Unidentified pathogenic mechanisms common to nephrolithiasis and hypertension may be responsible for the development of both disorders.

Nephrolithiasis and risk of hypertension.

A positive association between nephrolithiasis and blood pressure has been suggested in previous studies. However, controversy remains, due to methodological problems in some of the previous studies and absence of prospective data. We evaluated the relationship between nephrolithiasis and the risk of hypertension in a cohort of 51,529 men followed prospectively for 8 years. Information was obtained by biennial mailed questionnaires. At baseline in 1986, 4111 (8.0%) subjects reported a history of nephrolithiasis and 11,623 (22.6%) a diagnosis of hypertension. A positive association was found between the two disorders (age adjusted odds ratio [OR]: 1.31; 95% confidence interval [CI]: 1.30 to 1.32). Among men who reported both disorders, 79.5% reported that the occurrence of nephrolithiasis was prior to or concomitant with the diagnosis of hypertension. Among men without hypertension at baseline, the odds ratio for incident hypertension in men with a history of nephrolithiasis compared with those without was 1.29 (95% CI: 1.12 to 1.41; adjusted for age, body mass index, and intake of calcium, sodium, potassium, magnesium, and alcohol). The occurrence of incident nephrolithiasis during follow-up was similar in men with hypertension at baseline compared with that in men without (adjusted OR: 0.99, 95% CI: 0.82 to 1.21). These data support the hypothesis that prior occurrence of nephrolithiasis increases the risk of subsequent hypertension.

Blood pressure and angiotensin converting enzyme inhibitor use in hypertensive patients with chronic renal insufficiency.

BACKGROUND: Hypertension treatment is important in managing chronic renal insufficiency (CRI). Little is known, however, about the blood pressure (BP) control achieved or the pattern of antihypertensive drug prescription among CRI patients. METHODS: Using computerized medical records, we studied 3,089 adult hypertensive subjects treated at Brigham and Women's Hospital (Boston, MA) from 1990 through 1998. All subjects had at least two serum creatinine measurements 2 years apart, at least two BP readings, and online weight (to estimate Cockcroft-Gault creatinine clearance [CrCl]). RESULTS: The average mean arterial pressure over time (mean MAP) was 103 +/- 9 mm Hg among those with CrCI >60 mL/min, 102 t 9 mm Hg among those with CrCl 41 to 60 mL/min. and 101 +/- 9 mm Hg among those with CrCl 21 to 40 mL/min. There were no significant differences in mean MAP among the different categories of renal function in the multivariate analysis (P = .26 for trend). The proportion of patients with final systolic BP < 160 mm Hg and diastolic BP <90 mm Hg was 68% and did not vary with renal function (P = .68 for trend). The proportion of subjects who were prescribed ACE inhibitors was 38% among those with CrCl >60 mL/min, 36% among those with CrCI 41 to 60 mL/min, and only 27% among those with CrCl 21 to 40 mL/min (P = .003 for trend). CONCLUSIONS: The BP control achieved among hypertensive CRI subjects, although no worse than that among those without CRI, was found to be suboptimal. Patients with CrCl 21 to 40 mL/min were less likely to be prescribed ACE inhibitors than were those with CrCl >60 mL/min. Improvement is needed in the clinical management of these factors that can influence the progression of CRI.

High body mass index and hypercholesterolemia: risk of hypertensive disorders of pregnancy.

OBJECTIVE: To examine the relationship between pregravid body mass index (BMI), elevated cholesterol level, and the development of hypertensive disorders of pregnancy. METHODS: We studied 15,262 women who gave birth between 1991 and 1995. Pregravid exposures including BMI and self-reported history of elevated cholesterol were ascertained by biennial mailed questionnaires. Gestational hypertension or preeclampsia was confirmed by medical record review according to standard criteria. Proportional hazards analysis was used to adjust for potential confounding variables. RESULTS: We confirmed 216 cases of gestational hypertension and 86 cases of preeclampsia. The risk of gestational hypertension increased as pregravid BMI increased (P < .01). Compared with women with a pregravid BMI of 21-22.9 kg/m2, the relative risk (RR) of gestational hypertension was 1.6 (95% confidence interval [CI] 1.0, 2.3) for women with BMI of 23-24.9 kg/m2, 2.0 (95% CI 1.3, 3.0) for BMI 25-29.9 kg/m2, and 2.6 (95% CI 1.6, 4.4) for BMI over 30 kg/m2. Leaner women (BMI less than 21 kg/m2) had a reduced risk (RR 0.7, 95% CI 0.4, 1.0). For preeclampsia, the RR of women with pregravid BMI over 30 kg/m2 was 2.1 (95% CI 1.0, 4.6) (P for trend 0.09). A history of elevated cholesterol was not associated with the risk of gestational hypertension (RR 0.9, 95% CI, 0.6, 1.4). In contrast, the RR of preeclampsia in women with a history of elevated cholesterol was 2.0 (95% CI 1.2, 3.3). CONCLUSION: Pregravid BMI and hypercholesterolemia could identify women at higher risk for hypertensive disorders during pregnancy.

A prospective study of pregravid oral contraceptive use and risk of hypertensive disorders of pregnancy.

Oral contraceptive use is associated with hypertension, dyslipidemias, and insulin resistance, all of which also characterize hypertensive disorders of pregnancy. In this prospective cohort study, the association of oral contraceptive use before pregnancy and the risk of gestational hypertension and preeclampsia was assessed. Between 1991 and 1995, 3973 nulliparous women who reported their first pregnancy lasting > or = 6 months were studied. Pregravid exposures were collected by biennial mailed questionnaires, and cases were confirmed by medical record review. Recent oral contraceptive use was defined as use within 2 years of pregnancy. Proportional hazards analysis was used to adjust for potential confounding variables. During the 4 years of follow-up, 133 (3.3%) women with gestational hypertension and 62 (1.6%) with preeclampsia were identified. Twenty-five percent of women who did not develop these disorders were recent users of oral contraceptives, compared with 19% (p = 0.11) of women who developed gestational hypertension and 30% (p = 0.38) who developed preeclampsia. Mean duration of prior oral contraceptive use was similar for cases and noncases. Compared with never and past users, the multivariate relative risk among recent users for developing gestational hypertension was 0.7 (95% confidence interval (CI), 0.4-1.0) and for preeclampsia was 1.3 (95% CI, 0.8-2.4). Among recent users who had used oral contraceptives for > or = 8 years, the relative risk for gestational hypertension was 0.6 (95% CI, 0.3-1.2) and for preeclampsia was 2.1 (95% CI, 1.1-4.2). When the analysis was restricted to women who had never smoked, the risk for gestational hypertension was 0.2 (95% CI, 0.1-0.9) and for preeclampsia was 4.1 (95% CI, 1.9-8.7). Thus, recent use of oral contraceptives was associated with a reduced risk for developing gestational hypertension. In contrast, there was a suggestion that recent use was associated with an increased risk of developing preeclampsia, but only among women who had used these agents for > or = 8 years.

PIP: This article presents a prospective study on the relationship between pregravid oral contraceptive use and the risk of pregnancy-related hypertensive disorders. Oral contraceptives have been known to increase the risk to hypertension, dyslipidemias and insulin resistance, which characterize hypertensive disorders of pregnancy. This study examines this presumption by employing 3973 nulliparous women with pregnancies lasting 6 months during 1991-95. Data were taken from the results of biennial questionnaires and examination of prenatal records. Follow-up for the past 4 years identified 133 (3.3%) women with gestational hypertension and 62 (1.6%) with preeclampsia. Recent oral contraceptive use within 2 years of pregnancy was inversely associated with the development of gestational hypertension but was directly associated with preeclampsia. Compared with never users and past users, multivariate relative risk among recent users for the development of gestational hypertension was 0.7 (95% CI, 0.4-1.0) and of preeclampsia was 1.3 (95% CI, 0.8-2.4). Recent use of oral contraceptives (8 or more years) predisposes to a 0.6 risk for gestational hypertension and a 2.1 risk for preeclampsia. Thus, recent use of oral contraceptives was associated with a reduced risk for developing gestational hypertension. In contrast, there was a suggestion that recent use was associated with an increased risk of developing pre-eclampsia, but only among women who had used these agents for 8 or more years.

Epidemiologic evidence for the role of oxalate in idiopathic nephrolithiasis.

The importance of dietary and urinary oxalate in the formation of calcium oxalate kidney stones is widely accepted. Although the epidemiologic evidence for the role of oxalate remains largely indirect, recent prospective observations suggest its importance. The inverse association between dietary calcium intake and the risk of stone formation may be attributable to decreased gastrointestinal absorption of dietary oxalate and, thus, lower urinary oxalate concentrations. Further, the decreased risk of stone formation in women who consume large doses of vitamin B6 may be secondary to decreased oxalate production. The increased risk of nephrolithiasis observed with increasing body size may also be secondary to increased endogenous oxalate production. However, the frequency of hyperoxaluria is not substantially different in cases and controls for either sex. Notably, men have both higher stone incidence rates and higher mean urinary oxalate concentrations than women. Additional studies are needed to determine more precisely the role of dietary oxalate. More valid and comprehensive information on the oxalate content of food are desperately needed. Because the data on dietary oxalate are inconclusive, the routine restriction of dietary oxalate needs to be reexamined.

Dietary factors and kidney stone formation.

Kidney stone disease is a substantial health problem associated with significant pain and suffering, as well as economic costs. Over $2 billion were spent in 1986 on stone disease, the majority on treatment of existing stones and only a small percentage on prevention. Clearly, efforts to prevent or at least reduce the likelihood of developing a kidney stone would be an important component of the care of patients at risk. In particular, modifiable dietary factors appear to play an important role in the formation of calcium oxalate stones--the type of stone formed in the vast majority of cases. Once secondary causes of stone formation, such as hyperparathyroidism and renal tubular acidosis, are excluded, dietary counselling is a prudent and effective element of the therapeutic regimen and kidney stone prevention program. Specifically, for individuals who have a history of a calcium-containing kidney stone, important dietary recommendations should include the following: Achieve adequate fluid intake to produce at least 2 liters of urine per day. Avoid calcium restriction (except in the rare instances of excessive intake of greater than several grams per day). It is recommended a dietary intake of elemental calcium of at least 800 mg/day (the current RDA for adults) to prevent a negative calcium balance, bone mineral loss, and increased intestinal absorption of oxalate. At present, there is no evidence to support the belief that calcium restriction is beneficial and current data suggest that it may in fact be harmful.(ABSTRACT TRUNCATED AT 250 WORDS)

Fructose consumption and the risk of kidney stones.

Fructose consumption has markedly increased over the past decades. This intake may increase the urinary excretion of calcium, oxalate, uric acid, and other factors associated with kidney stone risk. We prospectively examined the relationship between fructose intake and incident kidney stones in the Nurses' Health Study I (NHS I) (93,730 older women), the Nurses' Health Study II (NHS II) (101,824 younger women), and the Health Professionals Follow-up Study (45,984 men). Food frequency questionnaires were used to assess free fructose and sucrose intake every 4 years. Total-fructose intake was calculated as free fructose plus half the intake of sucrose, and expressed as percentage of total energy. Cox proportional hazard regressions were adjusted for age, body mass index (BMI), thiazide use, caloric intake, and other dietary factors. We documented 4902 incident kidney stones during a combined 48 years of follow-up. The multivariate relative risks of kidney stones significantly increased for participants in the highest compared to the lowest quintile of total-fructose intake for all three study groups. Free-fructose intake was also associated with increased risk. Non-fructose carbohydrates were not associated with increased risk in any cohort. Our study suggests that fructose intake is independently associated with an increased risk of incident kidney stones.