Underweight body mass index is a risk factor of mortality in outpatients with nocturia in Japan

In this study, we showed that underweight BMI, as well as lower Physical Component
Summary of Short Form-36 item scores and high Charlson Comorbidity Score, was a risk
factor of mortality of nocturic outpatients in two general hospitals in Japan (Kurashiki
Central Hospital and Kyoto University Hospital).

Of note, high BMI is suggested as a risk factor for nocturia 16]. Therefore, a higher BMI population tends to be more nocturic than others, similar
to metabolic syndrome. However, whether BMI is related to mortality of nocturic patients
is unknown. BMI did not have any significant interaction with Charlson Comorbidity
Score or Physical Component Summary of Short Form-36 item, indicating that participants
did not tend have low BMI simply because they were ill. It has recently been reported
that BMI is inversely related to all-cause mortality in elderly people 17], 18]. A large study conducted in Japan showed that a low BMI in elderly people was associated
with an increased risk of all-cause mortality, and the results were essentially unchanged,
even when the analyses were conducted in those who did not have cancer, cardiovascular
disease, or stroke 17]. Moreover, higher BMI patients had improved survival rate in decompensated congestive
heart failure 19] and in chronic heart failure 20]. This paradoxical phenomenon was extended to the general population in a systemic
review and meta-analysis 21]. The exact reasons are not clear, but explanations for this paradox are that lean
mass acts as a nutritional preserve and thin older patients may have less immune response
22]. These factors may apply to nocturic elderly people.

In the present study, the cause of death largely depended on the comorbidities. This
is considered to be because subjects were outpatients with nocturia from two relatively
large general hospitals, although the survival rate of the nocturic patients in the
present study was not lower than that of the Japanese population calculated using
age- and sex-specific population estimates released by the Japanese Ministry of Internal
Affairs and Communications (using http://www.e-stat.go.jp/SG1/estat/XlsdlE.do?sinfid=000000090264; data not shown). Therefore, we re-analyzed particular groups selected with Charlson
Comorbidity Score between 0 and 2 (n = 166) in the same manner (Additional file 1). The result showed a clearer impact of BMI solely on the mortality, with hazard
ratio of 0.73 (95 % CI 0.62-0.88) in multivariate analysis. The Charlson Comorbidity
Score was not significantly related to the mortality in this particular group, indicating
that multiple comorbidities rather than the individual factor could drive the event.
In addition, the overweight BMI group had a significantly better survival rate than
the normal BMI group, with hazard ratio of 3.00 (p  0.05, 95 % CI = 1.01–8.94). This result suggests that although obesity is reported
to be a risk factor of nocturia, the overweight BMI is a favorable factor of survival
in nocturic outpatients without comorbidity or with relatively mild one. This paradox
can be compatible to the reported relationship between mortality and BMI after fracture
23].

There are several study limitations in this study. The purpose of this study was to
assess the association of BMI and all-cause mortality, while further detailed study
into the influence of BMI on the cause-specific mortality would be variable. The association
between nocturia and falls/fractures, and its relation to mortality was reported 6], 24]–26]. However, the low incidence of death in the present was not enough to evaluate it
and we cannot find any case that had a direct relation to fractures and death in the
present study except the case of traffic accident. The low incidence of death might
not have sufficient power to evaluate the factor of death in nocturic patients, which
indicate that the other covariates examined might have a relation to death. Age or
sex-related disease could be associated with weight loss and death 17], 27]. In addition, it cannot be denied that other undetected factors are related to the
mortality risk increased in low-BMI nocturic patients. Only one series of measures
was obtained from participants, even though the survival rates was referred with that
of the Japanese population calculated using age- and sex-specific population estimates
released by the Japanese Ministry of Internal Affairs and Communications. This design
makes it difficult to ascribe directionality to any other observed effects. Other
limitations of this study are that participants were all Japanese, so the relationship
of the BMI and mortality might be different in other countries. The lowest risk of
mortality was observed in the middle and elderly Japanese people with BMI between
21 and 27 27]. Although the WHO expert consultation agreed the WHO BMI cut-off points retained
as international classifications, but the Asians generally have a higher percentage
of body fat than Caucasians of the same age, sex, and BMI 28]. Further study is warranted in more ethnically diverse populations. Taking into account
these limitations, we believe that our results give novel insights into risk factors
of mortality in nocturic patients.