Thus, the major criticism of observational studies Selleck Fulvestrant is that results may be due to reverse causality (such as already unwell participants) and/or unmeasured bias or confounding (such as obesity and lack of PA), which RCTs attempt to take into account by randomization. This review has attempted to address some of these issues by stratification and sensitivity analyses. Quality of included studies When prospective studies were stratified by

the journal quality ratings score (�R6 vs lower),19 the association between low 25OHD and increased hypertension was both significant and not heterogeneous in the better-quality studies23�C26,28 (score �R6, RR =0.67 (0.51�C0.88); score <6, RR =0.86 (0.71�C1.05)) (Figure 2C). A similar pattern occurred Alizarin in cross-sectional studies, although the effect was not quite as marked in that all the studies remained significant in their category and also had no heterogeneity, but the ��higher quality�� 33,35,40,41 studies showed a stronger association between lower 25OHD levels and hypertension vs ��moderate quality��34,37�C39,43,48 (score =6, OR =0.79 (0.73�C0.87); score =5, OR =0.72 (0.65�C0.80); score =4, OR =0.86 (0.80�C0.93)) (Figure 3C). Heterogeneity and publication bias As with the previous meta-analyses, there

was no publication bias reported, probably due to the strict criteria used for selecting the studies to be used. However, in contrast to the two previous meta-analysis,7,8 which reported no heterogeneity in their results, this

present meta-analysis reported heterogeneity among studies of blood 25OHD concentrations and hypertension (in both prospective and cross-sectional studies) (Tables 2 and ?and4).4). The previous meta-analyses restricted their study selection to defined populations (eg, primarily Caucasian from either Europe or the US). The heterogeneity reported in the present meta-analysis is probably due to the wide scope of the literature search in demographic range (age, gender, country location, and ethnicity) of the studies assessed and also the different 25OHD assay technologies used. Demography and ethnicity The age range in this review was 18�C96, and the effect of low 25OHD on hypertension remained significant in both younger and older strata and somewhat surprisingly, was markedly stronger in those aged <55, and in females in prospective and cross-sectional data (Figures 2D and ?and3D3D). When it was possible to investigate gender separately, heterogeneity disappeared in both prospective and cross-sectional studies, but the associations became nonsignificant in the prospective studies, probably due to lower sample sizes. Females did seem to have a greater degree of association of hypertension risk with low vitamin D, especially at a younger age.