Nocturia, Sleep-Disordered Breathing, and Cardiovascular Morbidity in a Community-Based Cohort

Background: Nocturia has been independently associated with cardiovascular morbidity and all-cause mortality, but such studies did not adjust for sleep-disordered breathing (SDB), which may have mediated such a relationship. Our aims were to determine whether an association between nocturia and cardiovascular morbidity exists that is independent of SDB. We also determined whether nocturia is independently associated with SDB. Methodology/Principal Findings: In order to accomplish these aims we performed a cross-sectional analysis of the Sleep Heart Health Study that contained information regarding SDB, nocturia, and cardiovascular morbidity in a middle-age to elderly community-based population. In 6342 participants (age 63±11 [SD] years, 53% women), after adjusting for known confounders such as age, body mass index, diuretic use, diabetes mellitus, alpha-blocker use, nocturia was independently associated with SDB (measured as Apnea Hypopnea index >15 per hour; OR 1.3; 95%CI, 1.2-1.5). After adjusting for SDB and other known confounders, nocturia was independently associated with prevalent hypertension (OR 1.23; 95%CI 1.08-1.40; P = 0.002), cardiovascular disease (OR 1.26; 95%CI 1.05-1.52; P = 0.02) and stroke (OR 1.62; 95%CI 1.14-2.30; P = 0.007). Moreover, nocturia was also associated with adverse objective alterations of sleep as measured by polysomnography and self-reported excessive daytime sleepiness (P<0.05). Conclusions/Significance: Nocturia is independently associated with sleep-disordered breathing. After adjusting for SDB, there remained an association between nocturia and cardiovascular morbidity. Such results support screening for SDB in patients with nocturia, but the mechanisms underlying the relationship between nocturia and cardiovascular morbidity requires further study. MeSH terms: Nocturia, sleep-disordered breathing, obstructive sleep apnea, sleep apnea, polysomnography, hypertension

Proportions and numbers of patients with reported frequency of nocturia.

<p>Participants were queried as to how often in the prior year, did they awaken to go to the bathroom: never, rarely (1/month or less), sometimes (2–4/month), often (5–15/month), and almost always (16–30/month).</p

Participant Characteristics.

<p>Kg/m² = kilogram/meter²; FEV1 = Forced expiratory volume; hr = hour; proportions compared by Chi square; Mann-Whitney test for non-parametrics (presented as median and interquartile range); unpaired t-test for parametric variables (presented as mean ± SD); AHI = apnea-hypopnea index.</p

Association between nocturia and presence of sleep-disordered breathing based upon different apnea-hypopnea index (AHI) thresholds are shown as odds ratio (<i>symbol</i>) and 95% confidence intervals (<i>y-error bars</i>).

<p>Odds ratios and respective confidence intervals that were adjusted for confounders (<i>left panel</i>) and unadjusted for confounders (<i>right panel</i>) are shown. The x-axis of each panel represents nocturia expressed as a dichotomous categorical variable (nocturia present or absent) by progressively increasing the threshold level of collapse from ‘rarely’ to ‘always’ to yield four different dichotomous variables for nocturia. The cluster of three symbols with corresponding error bars for each definition of nocturia correspond to variable AHI thresholds for nocturia from left-to-right (>15, >10 and >5 per hour, respectively). For nocturia defined as greater than rarely (<i>closed triangle</i>) only one adjusted odds ratio is shown (<i>left panel</i>) because multivariate regression was performed only if univariate regression was significant at P<0.05 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030969#s2" target="_blank">methods</a>).</p

Variables Associated With Presence Of Nocturia.^†

<p>AHI = respiratory disturbance index; BMI = body mass index; FEV₁ = forced expiratory volume in one second; CI = confidence interval;</p><p>*dichotomous variables;</p>†<p>continuous variable.</p>§<p>Multiple regression that adjusts for age, BMI, alcohol, diuretics, FEV₁, α-blocker, coffee and soda.</p

Adjusted And Unadjusted Odds Ratios Of Associations with Hypertension.

<p>BMI = body mass index; AHI = apnea hypopnea index; diabetes = diabetes mellitus; B = estimated coefficient; SE = standard error; CI = confidence intervals.</p><p>*African-Americans compared to all other races combined;</p>†<p>per cigarette pack year;</p>‡<p>per inch neck circumference;</p>§<p>compared to absence of diabetes mellitus;</p>∥<p>per unit apnea-hypopnea index (>4% desaturation for hypopnea; <i>continuous variable</i>);</p><p>**compared to no diuretic;</p>††<p>per unit change in ratio.</p>§§<p>WASO = time awake after sleep onset;</p>∥∥<p>Arousals = arousal index expressed as arousals per hour of sleep;</p>‡‡<p>Nocturia was defined as ‘often’ (occurring at least 5 times per month).</p><p>***P<0.05;</p>†††<p>P<0.0001.</p

Adjusted Odds Ratios Of Associations Between Nocturia and Prevalent Cardiovascular Morbidity.

<p>*Adjusted for age, gender, race, smoking, diabetes mellitus, hypertension, systolic blood pressure, body mass index, total cholesterol, and high density lipoprotein levels.</p>†<p>Adjusted for sleep-disordered breathing (SDB; measured as apnea-hypopnea index) in addition to other confounders listed^*. Nocturia was defined as ‘often’ (occurring at least 5 times per month).</p>§<p>WASO = time awake after sleep onset;</p>∥<p>arousal index expressed as arousals per hour of sleep;</p>‡<p>P<0.05.</p

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