The main finding of the current study was that both BMI and WC were positively associated with postural changes in SBP, a measure of cardiovascular reactivity, in two independent populations from Germany. Furthermore, WC was no longer significantly related to postural changes in SBP once BMI was accounted for (either by direct adjustment or by using BMI-adjusted WC residuals in the models). These data suggest that adiposity in general is associated with a larger increase in postural changes in SBP, whereas body fat distribution as assessed by WC is not additionally related to postural changes in SBP beyond BMI. Our results also suggest that sitting BP levels may modify these associations.
The present findings are in agreement with the ARIC study, in which those with postural increases in SBP had higher BMIs than those in the reference group, while decreases in SBP were not significantly related to BMI [7]. Our results indicated that participants with obesity and high WC had higher values of postural changes in SBP than the overall study population. Likewise, the proportion of those with an increase in SBP upon standing was higher in the study population with obesity and high WC. Both exposures analyzed as continuous variables had similar associations with our outcome of interest across studies. Furthermore, once adjusted for BMI, the association between WC and postural changes in SBP was no longer significant. These data suggest that adiposity in general plays a major role, whereas abdominal body shape does not add further information.
Observational studies assessing health-related correlates of subtle postural BP increases are scarce; nevertheless, there are some potential mechanisms that may explain our findings. Under physiological circumstances, SBP drops by 5–10 mmHg after changing position [23], and factors such as the autonomic nervous system, intravascular volume, duration of erect posture, postprandial state and temperature (ambient, indoor and clinical) may influence the homeostasis of BP [24, 25]. Adiposity appears to impair autonomic function, potentially explained by alterations in insulin- and leptin-mediated sympathetic nervous system activation and baroreceptor dysfunction [26,27,28,29]. Interestingly and in line with our pooled estimates, previous studies have reported inverse relationships between BMI and OH in both men and women and in participants with neurological conditions [13, 28, 30]. Furthermore, recent evidence suggests that baroreflex sensitivity is impaired in metabolic syndrome [31] and that there is a link between inflammatory pathways and autonomic dysfunction and atherothrombosis in OH [32]. In addition, postural changes in SBP and BMI appear to have a joint genetic regulation by one or more genes on Chr. 13q [33]. In this context, questions arise as to when subtle postural changes in SBP begin in the lifetime and whether subtle postural increases in SBP are an earlier measure of the disease process or an independently acting mechanism [34]. In fact, a mean postural increase in SBP of 15.2 mmHg (range 11.3–43.8 mmHg) was associated with incident hypertension in the ARIC population; however, the association did not remain statistically significant after adjustments for seated SBP [7]. In addition, the ARIC study showed that values of postural change in SBP lower than 20 mmHg conferred elevated hazard ratios for lacunar stroke [8]. Similarly, higher odds for silent cerebral infarction were also observed for values of postural SBP change lower than 20 mmHg in an older population from Japan [35]. In the context of our findings, 9% of the participants in both the NAKO pretest and the MetScan studies had an increase of more than 10 mmHg in SBP upon standing. This frequency increased up to 16.9% in the NAKO pretest and to 12.4% in the MetScan study when only the population older than 60 years of age was considered. Taken together, one may speculate that these groups of participants might be at an elevated risk of overt clinical cerebrovascular events. Nevertheless, our cross-sectional design limits us from drawing clinical interpretations. Therefore, further research in the field of orthostatic changes in BP (in particular increases) and their clinical validation are essential to elucidate prevalence, incidence, and independent prognostic significance in different populations.
In contrast to previous population-based studies in which median values of postural changes in SBP were near 0 mmHg [4, 7], our mean value of postural dSBP was between 1.7 and 2.0 mmHg. This discrepancy might be partly explained by our exclusion criteria, in which study participants with a history of dizziness or syncope by a change in posture were not included as part of the extended BP protocol. Therefore, the present findings should be interpreted in relation to a population that excludes people with symptomatic systolic OH. Nevertheless, our aim was to study subtler responses to postural changes in SBP rather than clinical OH. Notably, 0.4% and 0.8% of the NAKO pretest and MetScan study participants, respectively, included in this study had asymptomatic postural dSBP ≥20 mmHg (data not shown). In addition, sex differences in BP regulation have been previously reported [12, 36], and there is evidence of sex differences in BP hemodynamics in overweight and obese populations [37]. However, we found similar responses to systolic postural changes among men and women. Consistent with the ARIC study [8], we observed less variability in orthostatic DBP changes than in postural SBP changes. Consequently, we focused our analysis on postural changes in SBP. Moreover, in a complementary analysis, we did not find associations between anthropometric measurements and dDBP, except for BMI in the NAKO pretest: a 5 kg/m2 higher BMI was associated with a 0.64 mmHg higher postural dDBP (95% CI 0.21–1.07) (data not shown).
We further evaluated the modification of the main effect by baseline, seated SBP, and our associations were stronger among those with higher levels of seated SBP. In hypertensive populations, baroreceptor responsiveness is impaired, possibly through different mechanisms [38]. It has been suggested that antihypertensive therapy may have an impact on postural changes in SBP [3, 39]; nonetheless, our findings were independent of antihypertensive treatment use.
One of the issues that emerges from our study is the moderate to good reliability in SBP measurement assessment. The superior reliability in MetScan, despite longer days in between measurements, might be explained by the number of trained nurses who performed the repeated measurements (4 nurses) compared to the NAKO pretest, in which more trained nurses participated in the pretest and might have influenced the intervariability. Symptomatic postural changes in BP are measured using a head-up tilt test; however, this test is not always available and warrants interpretation by a well-trained expert [39]. Thus, a corollary of this observation is that the protocol utilized here may be feasible in large population-based epidemiological studies. This is also underlined by the fact that the associations we observed between changes in SBP and BMI and WC were remarkably similar across the NAKO pretest and MetScan. In fact, in the fully adjusted models, a change of one SD in BMI was associated with a 0.21 SD and 0.19 SD increase in postural changes in BP in the NAKO pretest and MetScan studies, respectively. Similarly, a change of one SD in WC was associated with a 0.19 SD (NAKO pretest) and 0.23 SD (MetScan) increase in postural changes in BP, which were no longer statistically significant after adjustment for BMI (data not shown).
Furthermore, both supine-to-standing measurements and sitting-to-standing measurements are utilized in research settings. The ARIC study defined changes in SBP as the difference between standing and supine SBP, whereas in our study we used sitting instead of supine SBP. It has been suggested that the decrease in BP that occurs from transitioning from a supine to a standing position may be greater than that which occurs when changing position from sitting to standing [40]. If this is the case, then it is possible that our postural decreases in SBP were underestimated, as our study would have misclassified individuals who truly had postural decreases in SBP as not having them.
The strengths of this study include the standardized procedures used for postural BP measurements under similar indoor temperatures, the assessment of reliability of measurements and the replication of the findings in an independent population using continuous and categorical outcomes.
However, several limitations should be mentioned. First, due to the design, cross-sectional studies do not allow us to examine temporal relationships. Second, while we included known risk factors for OH as covariates, residual or unmeasured confounding (e.g., genetic predisposition [41], other neurological diseases [42]) needs to be considered when interpreting the results. Moreover, given that the covariates considered were all self-reported data, any potential misclassification of confounders should be taken into consideration. Nevertheless, the results were consistent when we analyzed confounding variables, taking missing data into account. Third, we cannot rule out that dSBP might be overestimated, as we excluded participants with a history of postural dizziness/syncope. Fourth, the MetScan study population was drawn as a convenience sample, and self-selection bias is likely with this approach. However, the characteristics were similar to those observed in the population-based sample from the NAKO pretest. Fifth, this study might have been underpowered to detect associations examining decreases in dSBP, and thus, the models should be interpreted with caution. Moreover, because it has been suggested that the assessment of DBP may be less reliable [34], we did not analyze postural changes in DBP (DBP usually increases by 5–10 mmHg upon standing due to peripheral vasoconstriction and reduction in cardiac stroke). Finally, one may argue that a considerable number of participants (n = 117) were excluded from the NAKO pretest due to the application of version 1 of the BP protocol. While we did not see differences in median values for BMI, WC or the prevalence of DM and stroke among those excluded, postural dSBP was slightly higher (Supplementary Table 4). Nevertheless, we were able to replicate the results in an independent population.
In conclusion, general adiposity was associated with postural changes in SBP in two independent populations, and this relationship was potentially driven by increases in postural SBP. Abdominal adiposity was not significantly related to changes in SBP once general adiposity was considered. Our results further suggest that seated BP levels seemed to modify this association.
Although the clinical implication of subtler postural changes in SBP is still unclear, our findings highlight the current knowledge gap in the epidemiology of orthostatic SBP dysregulation and the associated risk factors. Taken together, the mechanisms to maintain a normal BP postural response by adiposity may have implications for future research strategies. From a broader perspective, prospective studies that assess whether subtle increases in postural BP are associated with cardiovascular outcomes in different populations are of interest.
留言 (0)