Association of low blood pressure with suicidal ideation: a cross-sectional study of 10,708 adults with normal or low blood pressure in Korea

Most studies on blood pressure (BP) have focused on high BP, whereas studies on low BP are rare [1]. Unlike hypertension, constitutional low BP is not considered to be related to serious illness or death [1], and it is widely accepted that ‘the lower the BP the better’ [2]. However, most existing studies on whether constitutional low BP (hereinafter referred as low BP) can lead to adverse health outcomes have shown that low BP is associated with physical or mental symptoms or disease [3, 4], except for a few studies [5, 6]. In a large cross-sectional study, Wessely [3] showed a relationship between systolic BP (SBP) and self-reported tiredness and feeling faint. Barret-Connor et al. [4] reported that men with a diastolic BP (DBP) < 75 mmHg had a significantly higher rate of depression. More recently, two large-scale prevalence studies in older individuals also suggested that low BP is associated with depression [7, 8]. Hildrum et al. [9] reported that low BP is associated with depression, anxiety, and comorbidities of anxiety and depression in a cross-sectional study of 60,799 patients in the general population. Recent studies on low BP aimed mainly to identify correlations with neurological aspects. Although the results are mixed, a number of studies have suggested that low BP is associated with cognitive impairment, dementia, or Alzheimer’s disease [10–12]. Qiu et al. [11] showed that extremely low DBP (≤65 vs. 66–90 mmHg) had an adjusted relative risk of 1.7 (95% confidence interval [CI], 1.1 to 2.4) for Alzheimer’s disease and 1.5 (95% CI, 1.0 to 2.1) for dementia. A 13-year prospective cohort study reported that both high and low BP are associated with poorer cognitive performance in elderly African-Americans [12].

It is biologically plausible that hypotension is associated with mental and neurological health problems. Many recent studies that have shown a relationship between low BP and cognitive impairment suggested low cerebral perfusion as the biological mechanism. Studies that have identified a link between low BP and depression also suggested that cerebral vascular perfusion is a contributing factor, and that overexpression of neuropeptide Y observed in both depression and low BP may mediate this relationship [13, 14].

Suicide is a leading cause of death worldwide, and over 800,000 people die from suicide every year [15]. As suicidal ideation is a key stage in the pathway leading to suicide, a greater understanding of its risk factors could help in the development of suicide prevention strategies [16, 17].

It is well established that mental disorders, such as depression, amplify suicidal ideation and suicide [18, 19], whereas the role of physical conditions is controversial [20]. In a systematic review conducted in 2016, dysfunction, malignant tumor diseases, neurological disorders, male genital disorders, arthritis/arthrosis, chronic obstructive pulmonary disease, and liver disease were consistently associated with suicidal behavior, but cardiovascular disease showed little association. However, in a large cross-national study, myocardial infarction (MI) and stroke, but not cancer, were associated with suicidal ideation [21]. Most population and register-based studies reported no association between diabetes mellitus (DM) and suicidal behavior [20].

Several studies have examined the relationship between BP and suicidal ideation, but all were concerned with high BP. Scott et al. [21] suggested an increased risk of suicidal ideation in a high BP group, after adjusting for other types of physical conditions and mental disorders, although the risk was marginally significant (odds ratio [OR] = 1.3, 95% CI, 0.89 to 1.19). In contrast, some studies have shown that hypertension is not associated with suicidal ideation in older individuals [22, 23].

Despite the suspicion that low BP is associated with depression, which is a potent risk factor for suicidal ideation, no studies have investigated the association between low BP and suicidal ideation. Hirsch et al. [18] suggested that trait positive affect is an important independent contributor for reducing suicidal ideation. Subsequently, Kim et al. [7] showed that low BP is related to depression, specifically to a low positive affect. These two studies make it even more plausible that the risk of suicidal ideation in individuals with low BP is high.

Although the majority of studies on hypotension and mental health have been limited to older populations, the prevalence of hypotension is much higher in young adults [3]. In addition, the clinical interventions for low BP differ between English-speaking countries and continental European countries. Therefore, studies on the health impacts of hypotension are needed for populations of young adults from various countries, ethnicities, and races.

The purpose of this study was to investigate the association between low BP and suicidal ideation among adults aged > 19 years in Korea. Low BP was analyzed according to different SBP criteria, to determine whether there is a quantitative relationship in which the risk of suicidal ideation increases with decreasing cut-off levels for low BP.

This population-based study showed an association between low BP and suicidal ideation in a large general population representing Korean adults. This is consistent with several earlier studies supporting a correlation between low BP and psychological symptoms, such as depression and anxiety, even though outcome variables are distinct [9, 26, 27]. In this study, four cut-off values were used to define low BP: SBP < 110, < 100, < 95, and < 90 mmHg. All of these hypotensive groups except the SBP < 110 mmHg group showed meaningful correlations with suicidal ideation. As this is the first report to explore the relationship between low BP and suicidal ideation, it was not possible to compare our results with those of other studies assessing the same outcome. Instead, we compared our results with those of Hildrum et al. [9], who evaluated the correlation between low BP and depression and anxiety, using a similar study design. ORs for the comorbidities of anxiety and depression in the lowest fifth percentile of SBP in their study were similar with ORs for suicidal ideation in the SBP < 95 mmHg group in our study; the proportion of subjects corresponding to the lowest fifth percentile of SBP in Hildrum et al. is similar to those in the SBP < 95 mmHg group in this study, suggesting that low BP might affect suicidal ideation to similar extent as it affects typical psychiatric symptoms.

Because there is little research on the factors that influence low BP, we used five multiple regression models including different covariates to assess the effects of the potential confounding variables more closely. The analyses showed stronger correlations in models II-V, which included more potential confounding variables compared with Model I, in which only basic adjustments were made for sex, age, BMI, and total cholesterol level. Not presented in the results here, but in an additional multivariate model that included occupation, LDL-cholesterol level, and hemoglobin level, this association was still significant. These additional findings further support a correlation between low BP and suicidal ideation. We adjusted for several major diseases, such as DM, stroke, MI/angina pectoris, and depression, with little change in the outcome (models IV and V). Other underlying diseases may be confounding variables, but a previous study suggested no difference in baseline diseases between subjects with hypotension and those with a normal BP. A longitudinal follow-up study of 1337 patients conducted between 1958 and 1999 revealed no differences in underlying diseases between patients with low BP and those with normal BP, including malignant diseases, pulmonary diseases, gastric ulcers, mental disorders, blindness, and valvular heart diseases, except anemia [28]. Medication of antidepressants, antipsychotics, anticonvulsants, antihypertensives, and others may be potential compounding variables. Among these, antidepressants, antidiabetes, treatment for stroke and MI/angina pectoris were available in KNHANES data and considered. However, multi-collinearity with the corresponding diseases was apparent and excluded from the final analysis. Subjects who were using antihypertensive medications were included among those defined as having hypertension.

There is no consensually accepted definition for low BP. Most experts consider SBP ≤ 90 mmHg and/or DBP ≤ 60 mmHg as hypotensive [29]. The World Health Organization defines low BP as SBP < 110 in men and SBP < 100 mmHg in women, regardless of DBP [30], whereas a German study stated that values of 100/60 mmHg are hypotensive [31] (quoted in [32]). Some studies have used various criteria, such as SBP < 120 or DBP < 75 (for elderly subjects) [4], SBP < 110 [2], and SBP < 100 mmHg [3], whereas other studies have used the lowest 5th centile [9] or tertile [6]. These different standards for low BP make it even more difficult for comparisons and evaluations of the effects of low BP. The present study offers a methodological advantage in this regard, as the relationship between low BP and suicidal ideation was checked for each SBP category (< 110, < 100, < 95, and < 90 mmHg), which allowed us to identify changes in the results according to different BP cut-off values and to verify which BP level was clinically significant. Patients with the lower BP cut-off showed a more pronounced tendency toward suicidal ideation in all models, suggesting the possibility that lower BP is associated with suicidal ideation. The OR for SBP < 110 mmHg did not differ from that for normal BP for suicidal ideation. In contrast, the lower BP groups, with cut-off values of SBP < 100, < 95, and < 90 mmHg, showed significantly higher levels of suicidal ideation in all covariate models, suggesting that SBP < 100 mmHg is relevant to the relationship between low BP and suicidal ideation. A considerable number of people (11% of the adult population in Korea) have SBP < 100 mmHg. The association between suicidal ideation and this BP level raises the assumption that not only quite low but relatively low BP can be associated with suicidal ideation.

A large size sample that represents the general population of adults is another strength of this study. Although the prevalence of low BP is higher in younger people [3, 33], the majority of studies on the association between low BP and psychiatric disturbances have paid attention to specific age groups [34, 35], particularly to the elderly [4, 7, 26, 27, 36], making it impossible to know the influence throughout all ages of adults.

The results of this study can be generalized to all Korean adults, as the statistics reflect the complex sampling design, non-response to the survey, and post-stratification in the analyses. When weighted, the risk of suicidal ideation in the low BP group increased compared with the unweighted results (OR = 1.20, 95% CI, 1.02 to 1.40; OR = 1.22, 95% CI, 0.98 to 1.50; and OR = 1.39, 95% CI, 0.96 to 1.96 for SBP < 100, < 95, and < 90 mmHg, respectively; unweighted results, model V). It is assumed that the relationship between low BP and suicidal ideation would be more evident by applying weights during the analyses, as the sample reflected a higher population of younger people in urban areas than in rural areas.

There are no published studies investigating the impact of low BP on somatic or psychiatric symptoms in a general adult population in Asia, although the prevalence of hypotension is much higher in younger adults. This study is the first in Asia to investigate the relationship between low BP and substantive psychiatric symptoms in a large general population which includes young adults.

Unlike low BP, high BP was not associated with suicidal ideation in this study. Despite not adjusting for all comorbid cardiovascular diseases but several diseases, which are far more common in hypertensive patients and which affect mental health negatively [37], no association with suicidal ideation was seen in the hypertensive group, further reinforcing the suspicion that low BP itself is related to suicidal ideation. These results are consistent with previous studies showing no significant correlation between high BP and suicidal ideation [22, 23]. However, because a large-scale study suggested a high risk of suicidal ideation in patients with hypertension [21], further studies are needed.

In all five covariate models, the ORs in the prehypertensive group consistently did not differ from those in the normal BP group. These results further support that only low BP, among the different BP levels, is related to suicidal ideation. In addition, although prehypertension may be a risk factor for cardiovascular diseases and should be managed, it does not have a negative impact on mental health [see Additional file 1]. It is assumed that low BP poses quite different health issues from those of higher BP.

The results of this study are in accordance with the BP-emotional dampening hypothesis which suggests that BP has inhibitory effect on overall negative emotional experience and pain perception [38]. Baroreflex sensitivity (BRS) is strongly doubted as a potential mechanism [39]. In high BP, where baroreceptor stimulation dominates, increased BRS results in stronger cortical inhibition [39]. By contrast, in individuals with low BP, who predominantly exhibit baroreceptor inhibition, high BRS is accompanied by reduced central nervous inhibition and thus increased cortical arousal [39]. In several studies supporting this hypothesis, higher BP was associated with dampened responses to negative emotional stimuli [40]. On the contrary, high level of anxiety, hostility, and worry were clearly prevalent in people with low BP who were prevailed with reduced BRS [38, 41]. Psychophysiological approaches to explore whether BRS mediates the link between low BP and suicidal ideation will help to understand the mechanism.

The biological mechanism for the relationship between low BP and negative health effects is not well established. However, studies have suggested that reduced cerebral perfusion in a patient with low BP might be related with depression. Reduced microvascular circulation and oxygen transfer have been hypothesized to be a cause for the physical fatigue in a patient with a low BP. Erythrocyte velocity decreased at very low BP (< 70 mmHg) in a capillary dynamics study using TV microscopy at different BP levels [42]. The hypothesis that inappropriate energy production and accumulation of metabolites are causes of physical fatigue has also been suggested; [32] However, no evidence supports it. Conversely, studies suggesting that depression causes low BP have indicated that overexpressed neuropeptide Y in a patient with low BP is likely to mediate depression [13, 43]. More in-depth biological studies are needed to explain the mechanism.

Although it is clear that mental disorders, such as depression, are related to suicidal ideation, physical conditions are not. The present study is the first to investigate the association between low BP and suicidal ideation, which is a concrete indicator of a negative psychiatric state, thus driving the need to re-evaluate the health implications of low BP. Mental health conditions including suicidal ideation needs to be carefully monitored among those with low BP.

Although many studies suggest that low BP is associated with neuropsychological problems, including depression, anxiety, cognitive dysfunction, and dementia, no studies have investigated the association between low BP and suicidal ideation. We found that low SBP is associated with suicidal ideation in a general population. The association was significant for low BP defined by a SBP < 100 mmHg, and the strength of the association increased as the strictness of the criteria for low BP increased. This significant association seen in hypotension was not present in the hypertensive or prehypertensive groups but was hypotension-specific. This study has the advantage of being a large general population-based study covering a wide range of ages and using different cut-off levels for low BP, so we could examine whether there was a quantitative relationship in which the risk of suicidal ideation increases as the cut-off level of low BP is lower.