HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies.

OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. DESIGN: Observational cohort study. METHODS: Patients (23 437) were followed prospectively for 104 921 person-years. We used Poisson regression models to identify factors independently associated with deaths from ADM and nADM. Analyses of factors associated with mortality due to nADM were repeated after excluding nADM known to be associated with a specific risk factor. RESULTS: Three hundred five patients died due to a malignancy, 298 prior to the cutoff for this analysis (ADM: n = 110; nADM: n = 188). The mortality rate due to ADM decreased from 20.1/1000 person-years of follow-up [95% confidence interval (CI) 14.4, 25.9] when the most recent CD4 cell count was <50 cells/microl to 0.1 (0.03, 0.3)/1000 person-years of follow-up when the CD4 cell count was more than 500 cells/microl; the mortality rate from nADM decreased from 6.0 (95% CI 3.3, 10.1) to 0.6 (0.4, 0.8) per 1000 person-years of follow-up between these two CD4 cell count strata. In multivariable regression analyses, a two-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality included lower CD4 cell count, older age, current/ex-smoking status, longer cumulative exposure to combination antiretroviral therapy, active hepatitis B infection and earlier calendar year. CONCLUSION: The severity of immunosuppression is predictive of death from both ADM and nADM in HIV-infected populations.

Independent relations of left ventricular structure with the 24-h urinary excretion of sodium and aldosterone

Objective: Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone.We investigated the independent associations of LVMI with the urinary excretion of both sodium and aldosterone. Design and method: We randomly recruited 317 untreated subjects from a White population (45.1%women; mean age 48.2 years).Measurements included echocardiographic left ventricular (LV) properties, the 24 h urinary excretion of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNaprox) and distal (RNadist) renal sodium reabsorption, assessed fromthe endogenous lithium clearance. Inmultivariable-adjusted models,we expressed changes in LVMI per 1 SD increase in the explanatory variables, while accounting for sex, age, systolic blood pressure and the waist-to-hip ratio. Results: LVMI increased independentlywith the urinary excretion of both sodium (+2.48 g/m2; P=0.005) and aldosterone (+2.63 g/m2; P=0.004). Higher sodium excretion was associated with increased mean wall thickness (MWT: +0.126 mm, P=0.054), but with no change in LV end-diastolic diameter (LVID: +0.12mm, P=0.64). In contrast, higher aldosterone excretion was associated with higher LVID (+0.54 mm; P=0.017), but with no change in MWT (+0.070mm; P=0.28).Higher RNadistwas associatedwith lower relativewall thickness (−0.81×10−2, P=0.017), because of opposite trends in LVID(+0.33 mm; P=0.13) and MWT (−0.130mm; P=0.040). LVMI was not associated with PRA or RNaprox. Conclusions: LVMI independently increased with both urinary sodium and aldosterone excretion. IncreasedMWT explained the association of LVMI with urinary sodium and increased LVID the association of LVMI with urinary aldosterone.

Effects of usual nutrient intake and vitamin D status on markers of bone turnover in Swiss adolescents.

OBJECTIVE: To evaluate the effects of nutrient intake and vitamin D status on markers of type I collagen formation and degradation in adolescent boys and girls. DESIGN: Cross-sectional study. SETTING: Canton of Vaud, West Switzerland. SUBJECTS: A total of 92 boys and 104 girls, aged 11-16 y. Data were collected on height, weight, pubertal status (self-assessment of Tanner stage), nutrient intake (3-day dietary record) and fasting serum concentration of 25-hydroxyvitamin D (25OHD), and markers of collagen formation (P1NP) and degradation (serum C-terminal telopeptides: S-CTX). RESULTS: Tanner stage was a significant determinant of P1NP in boys and girls and S-CTX in girls. Of the nutrients examined, only the ratio of calcium to phosphorus (Ca/P) was positively associated with P1NP in boys, after adjustment for pubertal status. 25OHD decreased significantly at each Tanner stage in boys. Overall, 15% of boys and 17% of girls were identified as being vitamin D insufficient (serum 25OHD <30 nmol/l), with the highest proportion of insufficiency at Tanner stage 4-5 (29%) in boys and at Tanner stage 3 (24%) in girls. A significant association was not found between 25OHD and either bone turnover marker, nor was 25OHD insufficiency associated with higher concentrations of the bone turnover markers. CONCLUSIONS: The marked effects of puberty on bone metabolism may have obscured any possible effects of diet and vitamin D status on markers of bone metabolism. The mechanistic basis for the positive association between dietary Ca/P ratio and P1NP in boys is not clear and may be attributable to a higher Ca intake per se, a critical balance between Ca and P intake or higher dairy product consumption. A higher incidence of vitamin D insufficiency in older adolescents may reflect a more sedentary lifestyle or increased utilisation of 25OHD, and suggests that further research is needed to define their requirements. SPONSORSHIP: Nestec Ltd and The Swiss Foundation for Research in Osteoporosis.