LONG SLEEP DURATION AND RISK OF INCREASED ARTERIAL STIFFNESS IN MALES http://dx.doi.org/10.5665/sleep.3920
Long Sleep Duration Associated With a Higher Risk of Increased Arterial Stiffness in Males
Tsai-Chen Tsai, MD1; Jin-Shang Wu, MD, MS1,2; Yi-Ching Yang, MD, MPH1,2; Ying-Hsiang Huang, MD, MPH1; Feng-Hwa Lu, MD, MS1,2; Chih-Jen Chang, MD1,2 Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC; 2Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
1
Study Objectives: We aimed to examine the association between sleep duration and arterial stiffness among adults of different ages, because to date there has been only one study on this relationship, which was confined to middle-aged civil servants. Design: Cross-sectional study. Setting: A health examination center in National Cheng Kung University Hospital, Taiwan. Participants: A total of 3,508 subjects, age 20–87 y, were enrolled after excluding those with a history of cerebrovascular events, coronary artery disease, peripheral artery disease, and taking lipid-lowering drugs, antihypertensives, hypoglycemic agents, and anti-inflammatory drugs, from October 2006 to August 2009. Interventions: N/A. Measurements and Results: Sleep duration was classified into three groups: short (< 6 h), normal (6–8 h) and long (> 8 h). Arterial stiffness was measured by brachial-ankle pulse-wave velocity (baPWV), and increased arterial stiffness was defined as baPWV ≥ 1400 cm/sec. The sleep duration was different for subjects with and without increased arterial stiffness in males, but not in females. In the multivariate analysis for males, long sleepers (odds ratio [OR] 1.75, P = 0.034) but not short sleepers (OR 0.98, P = 0.92) had a higher risk of increased arterial stiffness. In addition, age, estimated glomerular filtration rate, hypertension, diabetes, total cholesterol/high-density lipoprotein cholesterol ratio, cigarette smoking, and exercise were also independently associated factors. However, in females, neither short nor long sleep duration was associated with increased arterial stiffness. Conclusions: Long sleep duration was associated with a higher risk of increased arterial stiffness in males. Short sleepers did not exhibit a significant risk of increased arterial stiffness in either sex. Keywords: arterial stiffness, brachial-ankle pulse-wave velocity, cardiovascular disease, sleep duration Citation: Tsai TC, Wu JS, Yang YC, Huang YH, Lu FH, Chang CJ. Long sleep duration associated with a higher risk of increased arterial stiffness in males. SLEEP 2014;37(8):1315-1320.
INTRODUCTION Epidemiological studies show that both short and long sleep duration are associated with increased risk of obesity, diabetes, hypertension, cardiovascular disease, and all-cause mortality.1–3 The mechanism of the association between sleep duration and cardiovascular disease remains unclear, although previous studies show that changes in sleep duration are associated with metabolic alteration,4 increased sympathetic nervous activity,5 and inflammatory pathways.6,7 Because increased arterial stiffness is also a predictor of fatal and nonfatal cardiovascular events and all-cause mortality,8–11 it can be seen as a link between sleep duration and cardiovascular outcomes. Arterial stiffness is associated with atherosclerosis at various sites in the vascular tree.12–14 Arterial stiffness is mainly caused by stimulation of an inflammatory process, overproduction of abnormal collagen, and decreased quantities of normal elastin.15 Of the several noninvasive methods available to assess arterial stiffness, pulse-wave velocity (PWV) is the most
A commentary on this article appears in this issue on page 1279. Submitted for publication November, 2013 Submitted in final revised form January, 2014 Accepted for publication January, 2014 Address correspondence to: Chih-Jen Chang, Department of Family Medicine, National Cheng Kung University Hospital, 138, Sheng Li Road, Tainan, 70403, Taiwan, ROC; Tel: +886-6-2353535 ext 5355; Fax: +8866-2386650; E-mail: [email protected] SLEEP, Vol. 37, No. 8, 2014
validated and reproducible.16,17 Although the gold standard is measuring central arterial stiffness via carotid-femoral PWV (cfPWV), this requires persistent lateral rotation of the patient’s neck and exposure of the inguinal region. In contrast, brachialankle PWV (baPWV) is more convenient to measure, because a pressure cuff only needs to be wrapped over the limbs while the subject is in a supine position. Studies also indicate that baPWV has a similar degree of association with cardiovascular risk factors and clinical events as cfPWV.10,18–22 To date, few studies have examined the relationship between sleep duration and arterial stiffness. Only one cross-sectional Japanese study revealed a positive association between longer sleep duration and increased arterial stiffness, as measured by baPWV, in males, but not females.23 However, their study subjects were confined to middle-aged (35–62 y) civil servants, without consideration of younger and older subjects. The aim of this study is thus to examine the association between arterial stiffness and sleep duration in a Taiwanese population. METHODS The baseline data, including 7,565 adult examinees, were collected from a health examination center in National Cheng Kung University Hospital, a tertiary medical center in Tainan, Taiwan, from October 2006 to August 2009. All subjects completed a structured questionnaire, which included items to collect their demographic information, medical history, medication history, lifestyle habits (cigarette smoking, alcohol drinking, and regular exercise), and self-reported sleep duration and snoring frequency. After exclusion of individuals with
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a history of cerebrovascular events, coronary artery disease, peripheral artery disease with an ankle-brachial index (ABI) less than 0.9, those taking lipid-lowering drugs, antihypertensive drugs, hypoglycemic agents, or anti-inflammatory drugs, and incomplete data, a total of 3,508 subjects were enrolled for the final analysis. Cigarette smoking was classified as current smoker (at least one pack per month for at least the previous 6 mo) and noncurrent smoker. Alcohol drinking was classified as current drinker (at least once per week for at least the previous 6 mo) and noncurrent drinker. Regular exercise was defined as vigorous exercise at least three times per week. Sleep duration was assessed by the following question in the self-reported questionnaire: “On average, how many hours and minutes do you sleep per night?” We further classified sleep duration into three groups: short (< 6 h), normal (6–8 h), and long (> 8 h).24 Anthropometric measurements included body weight (minimal unit of measurement: 0.1 kg) and height (minimal unit of measurement: 0.1 cm). Body mass index (BMI) was calculated as weight (kg)/height (m2). Blood pressure (BP) was measured in a supine position with a BP monitor (1846SX; Johnson and Johnson, assembled in Mexico) after at least 15 min of rest. Hypertension was defined as systolic BP greater than 140 mmHg or diastolic BP greater than 90 mmHg. After 10 h of overnight fasting, all subjects underwent the following blood tests: fasting plasma glucose, hemoglobin (Hb)A1C, 2-h postload plasma glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride, and creatinine. Diabetes mellitus was defined as a fasting glucose level of 126 mg/dL or more, or a 2-h postload glucose level of 200 mg/dL or more, or HbA1C more than or equal to 6.5%. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. An increased atherosclerosis risk was defined as a TC/ HDL-C ratio of more than 5. Arterial stiffness was measured by baPWV, using a noninvasive vascular screening device (BP-203RPE II; Colin Medical Technology, Komaki, Japan) with four pneumatic pressure cuffs over bilateral brachial arteries and tibial arteries, after 5 min of rest in the supine position. Heart rate and ABI were measured concurrently with PWV measurement. The baPWV value was calculated as the distance traveled by the pulse wave divided by the time taken to travel this distance. Increased arterial stiffness was defined as baPWV ≥ 1400 cm/sec. Statistical Analysis All statistical analyses were performed using the 17th version of the SPSS (Chicago, IL) software. The subjects were classified into those with and without increased arterial stiffness. Clinical characteristics in the study are presented as means ± standard deviation (SD) or percentage. χ2 tests were used to compare the categorical variables between groups. In addition, the comparisons of the continuous variables were analyzed using Student’s t-test between groups. Analysis of covariance (ANCOVA) was used to compare the baPWV values among subjects with different sleep durations by sex. Finally, we used multiple logistic regressions to explore the relationship between sleep duration and arterial stiffness. Statistical significance was defined as P < 0.05. SLEEP, Vol. 37, No. 8, 2014
RESULTS Table 1 shows the comparisons of clinical characteristics between subjects with and without increased baPWV by sex. In both sexes, subjects with increased arterial stiffness were older; had a higher systolic and diastolic blood pressure, fasting plasma glucose, total cholesterol, TC/HDL-C ratio, and prevalences of hypertension and diabetes mellitus; and lower eGFR than those without increased arterial stiffness. In addition, BMI, triglycerides, HDL-C, and alcohol drinking were significantly different between female subjects with and without increased arterial stiffness. However, the sleep duration was different between subjects with and without increased arterial stiffness in males only. In males, based on ANCOVA, Figure 1 showed that long sleepers had a higher baPWV value than normal sleepers (adjusted mean: 1413.6 ± 17.8 versus 1348.9 ± 4.2 cm/ sec, P < 0.001). There was no significant difference in baPWV between short and normal sleepers (adjusted mean: 1342.2 ± 10.3 versus 1348.9 ± 4.2 cm/sec, P = 0.547). As for females, the baPWV values in normal, short, and long sleepers were 1266.0 ± 5.1, 1275.0 ± 11.8, and 1297.3 ± 19.7cm/sec, respectively. There were no significant differences in baPWV among these three groups. The results of the multiple logistic regression analysis on the relationship between sleep duration and baPWV in males and females are summarized in Table 2. In males, long sleepers (OR = 1.75, 95% confidence interval [CI] = 1.04–2.94), but not short sleepers (OR = 0.98, 95% CI = 0.72–1.35), had a higher risk of increased arterial stiffness after adjusting for other variables. In addition, age of 40–59 y versus younger than 40 y, age 60 y or older versus younger than 40 y, lower eGFR, hypertension, diabetes, TC/HDL-C ratio > 5, and cigarette smoking were independently associated with increased arterial stiffness, and regular exercise had an inverted relationship. In females, although age 40–59 y versus younger than 40 y, age 60 y or older versus younger than 40 y, BMI, hypertension and TC/ HDL-C ratio were the independently associated factors, both short and long sleep duration were not related to increased arterial stiffness. DISCUSSION Our results revealed that long sleep duration is associated with a higher risk of increased arterial stiffness in males, whereas no significant association was found for short sleepers of either sex, after adjusting for the potential confounding factors in a Taiwanese population. To the best of our knowledge, there has only been one cross-sectional study on the relationship between sleep duration and arterial stiffness as measured by baPWV.23 However, the study subjects in that study were mainly males, and confined to middle-aged Japanese civil servants. In addition, subjects with medications that would influence arterial stiffness were not excluded. In contrast, our study excluded subjects taking lipid-lowering drugs, antihypertensive agents, hypoglycemic agents, and anti-inflammatory drugs because previous research showed that arterial stiffness is mainly caused by an inflammatory process,15 and that a variety of pharmacological treatments are associated with changes in arterial stiffness.25 The results of the logistic regression analyses carried out in this work showed that only long sleep duration was associated
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Table 1—Clinical characteristics of study subjects with and without increased arterial stiffness by sex baPWV in Males
Age (y) Age group (y) < 40 40–59 ≥ 60 Body mass index (kg/m2) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Creatinine (mg/dL) eGFR (ml/min/1.73 m2) Fasting plasma glucose (mg/dL) Total cholesterol (mg/dL) Triglyceride (mg/dL) HDL-C (mg/dL) TC/HDL-C > 5 Sleep duration (hours) 8 Snoring ≥ 3/w Hypertension Diabetes mellitus Smoking Alcohol drinking Regular exercise ≥ 3/w
P value
< 1400cm/s (n = 1,418) 42.3 ± 9.6
≥ 1400 cm/s (n = 677) 52.7 ± 11.1
547 (38.6) 823 (58.0) 48 (3.4) 24.7 ± 3.3 115.9 ± 10.3 69.7 ± 8.3 0.96 ± 0.12 93.3 ± 15.1 88.6 ± 18.8 195.1 ± 35.8 136.5 ± 94.3 47.0 ± 11.5 377 (26.6)
75 (11.1) 433 (64.0) 169 (25.0) 24.8 ± 3.1 130.1 ± 15.5 79.6 ± 10.4 0.99 ± 0.35 88.1 ± 16.0 94.9 ± 24.6 204.3 ± 36.6 144.1 ± 93.0 47.0 ± 12.1 227 (33.5)
188 (13.3) 1184 (83.5) 46 (3.2) 352 (24.6) 60 (4.2) 54 (3.8) 325 (22.9) 365 (25.7) 209 (14.7)
94 (13.9) 532 (78.6) 51 (7.5) 175 (24.4) 213 (31.5) 88 (13.0) 172 (25.4) 175 (25.8) 84 (12.4)
< 0.001 < 0.001
0.216 < 0.001 < 0.001 0.009 < 0.001 < 0.001 < 0.001 0.085 0.957 0.001 < 0.001
0.978 < 0.001 < 0.001 0.211 0.958 0.150
baPWV in Females < 1400cm/s (n = 1,094) 42.3 ± 9.7
≥ 1400 cm/s (n = 319) 55.9 ± 9.4
423 (38.7) 635 (58.0) 36 (3.3) 22.2 ± 3.3 106.1 ± 11.0 61.7 ± 8.0 0.69 ± 0.19 102.4 ± 18.3 85.1 ± 12.3 189.9 ± 34.3 89.5 ± 53.4 60.1 ± 14.3 53 (4.8)
12 (3.8) 208 (65.2) 99 (31.0) 23.8 ± 3.3 128.6 ± 16.5 73.9 ± 10.0 0.73 ± 0.38 94.6 ± 20.0 93.6 ± 27.4 206.8 ± 41.3 124.3 ± 84.6 57.3 ± 14.6 48 (15.0)
165 (15.1) 876 (80.1) 53 (4.8) 102 (9.3) 16 (1.5) 29 (2.7) 35 (3.2) 53 (4.8) 99 (9.0)
45 (14.1) 250 (74.4) 24 (7.5) 39 (11.5) 96 (30.1) 39 (12.2) 4 (1.3) 4 (1.3) 33 (10.3)
P value
< 0.001 < 0.001
< 0.001 < 0.001 < 0.001 0.150 < 0.001 < 0.001 < 0.001 < 0.001 0.002 < 0.001 0.174
0.354 < 0.001 < 0.001 0.062 0.004 0.484
Data are expressed as means ± standard deviation or numbers (percentage). baPWV, brachial-ankle pulse-wave velocity; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein-cholesterol; TC, total cholesterol.
with a higher risk of increased arterial stiffness in male, but not in females. This is consistent with the study results from Yoshioka et al., who found that, compared with a reference group that reported an average of 7 h of sleep, long sleep duration was significantly associated with higher baPWV.23 The underlying mechanisms between long sleep duration and arterial stiffness are not clear, but the relationship may be related to the following factors: sleep fragmentation, fatigue, immune function, photoperiodic abnormalities, lack of challenge, depression, and underlying disease processes such as sleep apnea, heart disease, and failing health,24 which might suggest that long sleep is more strongly associated with cardiovascular outcomes and all-cause mortality than short sleep.1,3,26 In addition, inflammatory pathways may be another mechanism for the positive relationship between long sleep duration and increased arterial stiffness. Because Asian long sleepers had a higher inflammation status than short sleepers,27,28 the inflammatory process will cause dysregulation of collagen and elastin fibers of the vascular wall, leading to arterial stiffness.15 Furthermore, long sleepers reported difficulty falling asleep, awakening during the night, awakening too early, awakening unrefreshed, daytime sleepiness,29 and greater insomnia and sleeping pill use30 than normal sleepers. Thus, long sleep duration may be related to poor sleep SLEEP, Vol. 37, No. 8, 2014
quality, and poor sleep quality was found to be associated with insulin resistance,31 alteration of hypothalamic-pituitaryadrenal system activity,32 increased sympathetic activity,33 and endothelial function impairment.34,35 This may partially explain the association between long sleep duration and increased arterial stiffness. Further research is needed to explore their mechanism. With regard to sex differences in the risk of increased arterial stiffness, earlier studies revealed a linear relationship between CRP and PWV among late perimenopausal or postmenopausal women,36 and that the values of central pulse pressure and PWV were lower in hormone therapy users.37,38 These findings show that the female hormone may be a protective factor for arterial stiffness, and thus may account for the sex advantage found among females in this context. Both structural and functional changes in the arteries occur with the aging process. Sympathetic nerve activity elevation,39 endothelial dysfunction,40 and proinflammatory status41 induce vasoconstriction, smooth muscle cell hypertrophy, and elastin fragmentation with collagen synthesis, and then may lead to increased arterial stiffness with aging.42 Our study showed that hypertension and a TC/HDL-C ratio greater than 5 were independently associated factors of increased
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baPWV (cm/s)
baPWV (cm/s)
arterial stiffness, consistent with previous findings.43–45 Higher blood pressure increases the shearing stress of the artery, which Male Female induces arterial stiffening through endothelial dysfunction,43 P < 0.001 alterations in the extracellular matrix,44 and activation of the 1440 renin-angiotensin-aldosterone system.45 According to previous 1420 studies, the TC/HDL-C ratio is a superior measure of risk for 1400 P = 0.547 coronary heart disease compared with either TC or low-density 1380 lipoprotein cholesterol (LDL-C) levels.46,47 In addition, the 1360 cutoff point of five shows higher specificity and accuracy in 1340 Chinese populations when compared with using a LDL-C level 1320 of 130 mg/dL as the cutoff point.48 Dyslipidemia also has been 1300 shown to have a harmful effect on arterial stiffness through the 1280 mechanisms of endothelial dysfunction, reduced nitric oxide 8 bioavailability, and the inflammatory process.49 Sleep Duration (hours) Diabetes was found to be associated with increased arterial stiffness,50–52 and the mechanism underlying this may be related P = 0.124 to the inflammatory process and increased oxidative stress.50 In 1330 addition, advanced glycation end-products link with collagen 1320 in the vascular wall, resulting in irreversible cross-links, which 1310 P = 0.483 1300 are stiffer and less susceptible to hydrolytic turnover, and this 1290 leads to an increase in arterial stiffness.53 The only significant 1280 association found between diabetes and increased arterial 1270 stiffness in the current study was among males. This may be 1260 related to the lower statistical power with regard to the females’ 1250 data, because there was a lower prevalence of diabetes among 1240 women (4.8%) than men (6.8%) in this work. 1230 8 Our results showed that a higher BMI was positively related Sleep Duration (hours) to increased arterial stiffness in females only. The relationship between BMI and arterial stiffness remains unclear. Some Figure 1—Comparisons of brachial-ankle pulse-wave velocity studies show a positive association between BMI and aortic (baPWV) among subjects with different sleep durations by sex based PWV,54,55 whereas others find an inverse association between on analysis of covariance. BMI and baPWV in both sexes.56,57 Moreover, Rodrigues et al. found that BMI is not independently associated with increased aortic stiffness.58 The effects of BMI on arterial stiffness might be mediated by the intermediate parameters of Table 2—The adjusted odds ratios and 95% confidence intervals of multiple logistic regression analysis for cardiovascular risk factors. There was the relationship between sleep duration and increased arterial stiffness by sex a high correlation between BMI and Male Female TC/HDL-C ratio (r = 0.458) in current OR (95% CI) P value OR (95% CI) P value study. In addition, the high correlation Age group (y) coefficient exists between baPWV 40–59 vs. < 40 3.65 (2.70–4.92) < 0.001 7.78 (4.21–14.37) < 0.001 and the following variables: age ≥ 60 vs. < 40 21.67 (13.85–33.91) < 0.001 48.08 (23.16–99.85) < 0.001 (r = 0.592) and systolic (r = 0.668) and 0.98 (0.94–1.02) 0.237 1.06 (1.01–1.16) 0.011 Body mass index (kg/m2) diastolic blood pressures (r = 0.598). 0.99 (0.98–1.00) 0.040 0.99 (0.99–1.00) 0.204 eGFR (mL/min/1.73 m2) The effect of BMI on arterial stiffness Hypertension (yes vs. no) 10.40 (7.39–14.64) < 0.001 14.84 (8.20–26.87) < 0.001 might be caused by high collinearity Diabetes mellitus (yes vs. no) 2.36 (1.55–3.58) < 0.001 1.10 (0.56–2.15) 0.781 and mediated by age, blood pressure, and TC/HDL-C ratio. This may be a TC/HDL-C > 5 (yes vs. no) 1.39 (1.08–1.77) 0.009 2.12 (1.27–3.55) 0.004 partial explanation for the inconsisSleep duration (h) tent results in these earlier studies. < 6 vs. 6–8 0.98 (0.72–1.35) 0.920 0.86 (0.56–1.31) 0.476 Our study showed an inverse asso> 8 vs. 6–8 1.75 (1.04–2.94) 0.034 1.02 (0.48–2.15) 0.963 ciation between eGFR and increased Smoking (yes vs. no) 1.44 (1.11–1.87) 0.007 0.45 (0.13–1.62) 0.224 arterial stiffness in males. Chronic Alcohol drinking (yes vs. no) 0.95 (0.74–1.23) 0.700 0.40 (0.13–1.17) 0.092 kidney disease is associated with Regular exercise (yes vs. no) 0.69 (0.50–0.95) 0.025 1.09 (0.68–1.77) 0.717 increased arterial stiffness through the Snoring ≥ 3/week (yes vs. no) 0.95 (0.73–1.22) 0.670 0.89 (0.52–1.52) 0.676 mechanism of endothelial dysfunction, chronic inflammation and CI, confidence interval; eGFR, estimated glomerular filtration rate, HDL-C, high-density lipoproteinvascular calcification, and activation cholesterol; OR, odds ratio; TC, total cholesterol. of the renin-angiotensin-aldosterone SLEEP, Vol. 37, No. 8, 2014
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system.59,60 As for the influence of lifestyle status on arterial stiffness, smoking has been shown to be positively related to increased arterial stiffness,61 whereas regular aerobic exercise is associated with reduced arterial stiffness.62 In our study, there was only a significant association between lifestyle status and increased arterial stiffness in males. This may be explained by the lower number of female subjects who smoked and who exercised less regularly than male subjects. This study has several limitations, as follows. First, the cross-sectional design of this work means that it is not possible to establish a causal relationship between sleep duration and arterial stiffness. Second, self-reported sleep duration may have subjective errors, although Lauderdale et al. found that subjective estimates of sleep duration correlated highly with polysomnographic assessments.63 Third, we measured only the quantity but not the quality of sleep, although poor sleep quality scores on the Pittsburgh Sleep Quality Index have been found to be significantly related to various cardiovascular risk factors, such as diabetes and hypertension.64,65 Fourth, subjects with obstructive sleep apnea syndrome were not excluded in our study, and this condition has been found to be associated with increased arterial stiffness.66 Although we adjusted for the multiple confounding variables and snoring frequency, the effect of obstructive sleep apnea may not have been fully controlled for. In conclusion, long sleep duration was associated with a higher risk of increased arterial stiffness in males. Short sleepers did not exhibit a significant risk of increased arterial stiffness in either sex. In addition to cardiovascular risk factors and lifestyle, the results of this study show that sleep duration cannot be ignored when considering the prevention of cardiovascular disease. ABBREVIATIONS ABI, ankle-brachial index baPWV, brachial-ankle PWV BMI, body mass index BP, blood pressure cfPWV, carotid-femoral PWV eGFR, estimated glomerular filtration rate HDL-C, high density lipoprotein cholesterol LDL-C, low density lipoprotein cholesterol MDRD, Modification of Diet in Renal Disease PWV, pulse-wave velocity TC, total cholesterol DISCLOSURE STATEMENT This was not an industry supported study. This work was supported by the Department of Family Medicine, National Cheng-Kung University Hospital [Grant number NCKUHFM101-002]. The authors have indicated no financial conflicts of interest. REFERENCES
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28. Grandner MA, Buxton OM, Jackson N, Sands-Lincoln M, Pandey A, Jean-Louis G. Extreme sleep durations and increased C-reactive protein: effects of sex and ethnoracial group. Sleep 2013;36:769–79E. 29. Grandner MA, Kripke DF. Self-reported sleep complaints with long and short sleep: a nationally representative sample. Psychosom Med 2004;66:239–41. 30. Kripke DF, Garfinkel L, Wingard DL, Klauber MR, Marler MR. Mortality associated with sleep duration and insomnia. Arch Gen Psychiatry 2002;59:131–6. 31. Knutson KL, Van Cauter E, Zee P, Liu K, Lauderdale DS. Crosssectional associations between measures of sleep and markers of glucose metabolism among subjects with and without diabetes: the Coronary Artery Risk Development in Young Adults (CARDIA) Sleep Study. Diabetes Care 2011;34:1171–6. 32. Goodin BR, Smith MT, Quinn NB, King CD, McGuire L. Poor sleep quality and exaggerated salivary cortisol reactivity to the cold pressor task predict greater acute pain severity in a non-clinical sample. Biol Psychol 2012;91:36–41. 33. Zhang J, Ma RC, Kong AP, et al. Relationship of sleep quantity and quality with 24-hour urinary catecholamines and salivary awakening cortisol in healthy middle-aged adults. Sleep 2011;34:225–33. 34. Behl M, Bliwise D, Veledar E, et al. Vascular endothelial function and self-reported sleep. Am J Med Sci 2014;347:425–8. 35. Cooper DC, Ziegler MG, Milic MS, et al. Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep. J Sleep Res 2014;23:84–93. 36. Woodard GA, Mehta VG, Mackey RH, et al. C-reactive protein is associated with aortic stiffness in a cohort of African American and white women transitioning through menopause. Menopause 2011;18:1291–7. 37. Miura S, Tanaka E, Mori A, et al. Hormone replacement therapy improves arterial stiffness in normotensive postmenopausal women. Maturitas 2003;45:293–8. 38. Gompel A, Boutouyrie P, Joannides R, et al. Association of menopause and hormone replacement therapy with large artery remodeling. Fertil Steril 2011;96:1445–50. 39. Dinenno FA, Jones PP, Seals DR, Tanaka H. Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol Heart Circ Physiol 2000;278:H1205–10. 40. Donato AJ, Gano LB, Eskurza I, et al. Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol 2009;297:H425–32. 41. Wang M, Zhang J, Jiang LQ, et al. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension 2007;50:219–27. 42. Mirea O, Donoiu I, Plesea IE. Arterial aging: a brief review. Rom J Morphol Embryol 2012;53:473–7. 43. Landmesser U, Drexler H. Endothelial function and hypertension. Curr Opin Cardiol 2007;22:316–20. 44. Castro MM, Tanus-Santos JE. Inhibition of matrix metalloproteinases (MMPs) as a potential strategy to ameliorate hypertension-induced cardiovascular alterations. Curr Drug Targets 2013;14:335–43. 45. Mahmud A, Feely J. Arterial stiffness and the renin-angiotensinaldosterone system. J Renin Angiotensin Aldosterone Syst 2004;5:102–8. 46. Kinosian B, Glick H, Garland G. Cholesterol and coronary heart disease: predicting risks by levels and ratios. Ann Intern Med 1994;121:641–7. 47. Kinosian B, Glick H, Preiss L, Puder KL. Cholesterol and coronary heart disease: predicting risks in men by changes in levels and ratios. J Investig Med 1995;43:443–50.
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48. Wang TD, Chen WJ, Chien KL, et al. Efficacy of cholesterol levels and ratios in predicting future coronary heart disease in a Chinese population. Am J Cardiol 2001;88:737–43. 49. Wilkinson I, Cockcroft JR. Cholesterol, lipids and arterial stiffness. Adv Cardiol 2007;44:261–77. 50. Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 2008;371:1800–9. 51. Li CH, Wu JS, Yang YC, Shih CC, Lu FH, Chang CJ. Increased arterial stiffness in subjects with impaired glucose tolerance and newly diagnosed diabetes but not isolated impaired fasting glucose. J Clin Endocrinol Metab 2012;97:E658–62. 52. Stehouwer CD, Henry RM, Ferreira I. Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia 2008;51:527–39. 53. Lee AT, Cerami A. Role of glycation in aging. Ann N Y Acad Sci 1992;663:63–70. 54. Wildman RP, Mackey RH, Bostom A, Thompson T, Sutton-Tyrrell K. Measures of obesity are associated with vascular stiffness in young and older adults. Hypertension 2003;42:468–73. 55. Tuttolomondo A, Di Raimondo D, Di Sciacca R, et al. Arterial stiffness and ischemic stroke in subjects with and without metabolic syndrome. Atherosclerosis 2012;225:216–9. 56. Tomiyama H, Yamashina A, Arai T, et al. Influences of age and gender on results of noninvasive brachial-ankle pulse wave velocity measurement–a survey of 12517 subjects. Atherosclerosis 2003;166:303–9. 57. Budimir D, Jeroncic A, Gunjaca G, Rudan I, Polasek O, Boban M. Sexspecific association of anthropometric measures of body composition with arterial stiffness in a healthy population. Med Sci Monit 2012;18:CR65–71. 58. Rodrigues SL, Baldo MP, Lani L, Nogueira L, Mill JG, Sa Cunha R. Body mass index is not independently associated with increased aortic stiffness in a Brazilian population. Am J Hypertens 2012;25:1064–9. 59. Briet M, Burns KD. Chronic kidney disease and vascular remodelling: molecular mechanisms and clinical implications. Clin Sci (Lond) 2012;123:399–416. 60. Moody WE, Edwards NC, Chue CD, Ferro CJ, Townend JN. Arterial disease in chronic kidney disease. Heart 2013;99:365–72. 61. Doonan RJ, Hausvater A, Scallan C, Mikhailidis DP, Pilote L, Daskalopoulou SS. The effect of smoking on arterial stiffness. Hypertens Res 2010;33:398–410. 62. Tanaka H, Safar ME. Influence of lifestyle modification on arterial stiffness and wave reflections. Am J Hypertens 2005;18:137–44. 63. Lauderdale DS, Knutson KL, Yan LL, Liu K, Rathouz PJ. Self-reported and measured sleep duration: how similar are they? Epidemiology 2008;19:838–45. 64. Fiorentini A, Valente R, Perciaccante A, Tubani L. Sleep’s quality disorders in patients with hypertension and type 2 diabetes mellitus. Int J Cardiol 2007;114:E50–2. 65. Bruno RM, Palagini L, Gemignani A, et al. Poor sleep quality and resistant hypertension. Sleep Med 2013;14:1157–63. 66. Phillips CL, Butlin M, Wong KK, Avolio AP. Is obstructive sleep apnoea causally related to arterial stiffness? A critical review of the experimental evidence. Sleep Med Rev 2013;17:7–18.
Sleep Duration and Arterial Stiffness—Tsai et al.
Long Sleep Duration Associated With a Higher Risk of Increased Arterial Stiffness in Males
Tsai-Chen Tsai, MD1; Jin-Shang Wu, MD, MS1,2; Yi-Ching Yang, MD, MPH1,2; Ying-Hsiang Huang, MD, MPH1; Feng-Hwa Lu, MD, MS1,2; Chih-Jen Chang, MD1,2 Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC; 2Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
1
Study Objectives: We aimed to examine the association between sleep duration and arterial stiffness among adults of different ages, because to date there has been only one study on this relationship, which was confined to middle-aged civil servants. Design: Cross-sectional study. Setting: A health examination center in National Cheng Kung University Hospital, Taiwan. Participants: A total of 3,508 subjects, age 20–87 y, were enrolled after excluding those with a history of cerebrovascular events, coronary artery disease, peripheral artery disease, and taking lipid-lowering drugs, antihypertensives, hypoglycemic agents, and anti-inflammatory drugs, from October 2006 to August 2009. Interventions: N/A. Measurements and Results: Sleep duration was classified into three groups: short (< 6 h), normal (6–8 h) and long (> 8 h). Arterial stiffness was measured by brachial-ankle pulse-wave velocity (baPWV), and increased arterial stiffness was defined as baPWV ≥ 1400 cm/sec. The sleep duration was different for subjects with and without increased arterial stiffness in males, but not in females. In the multivariate analysis for males, long sleepers (odds ratio [OR] 1.75, P = 0.034) but not short sleepers (OR 0.98, P = 0.92) had a higher risk of increased arterial stiffness. In addition, age, estimated glomerular filtration rate, hypertension, diabetes, total cholesterol/high-density lipoprotein cholesterol ratio, cigarette smoking, and exercise were also independently associated factors. However, in females, neither short nor long sleep duration was associated with increased arterial stiffness. Conclusions: Long sleep duration was associated with a higher risk of increased arterial stiffness in males. Short sleepers did not exhibit a significant risk of increased arterial stiffness in either sex. Keywords: arterial stiffness, brachial-ankle pulse-wave velocity, cardiovascular disease, sleep duration Citation: Tsai TC, Wu JS, Yang YC, Huang YH, Lu FH, Chang CJ. Long sleep duration associated with a higher risk of increased arterial stiffness in males. SLEEP 2014;37(8):1315-1320.
INTRODUCTION Epidemiological studies show that both short and long sleep duration are associated with increased risk of obesity, diabetes, hypertension, cardiovascular disease, and all-cause mortality.1–3 The mechanism of the association between sleep duration and cardiovascular disease remains unclear, although previous studies show that changes in sleep duration are associated with metabolic alteration,4 increased sympathetic nervous activity,5 and inflammatory pathways.6,7 Because increased arterial stiffness is also a predictor of fatal and nonfatal cardiovascular events and all-cause mortality,8–11 it can be seen as a link between sleep duration and cardiovascular outcomes. Arterial stiffness is associated with atherosclerosis at various sites in the vascular tree.12–14 Arterial stiffness is mainly caused by stimulation of an inflammatory process, overproduction of abnormal collagen, and decreased quantities of normal elastin.15 Of the several noninvasive methods available to assess arterial stiffness, pulse-wave velocity (PWV) is the most
A commentary on this article appears in this issue on page 1279. Submitted for publication November, 2013 Submitted in final revised form January, 2014 Accepted for publication January, 2014 Address correspondence to: Chih-Jen Chang, Department of Family Medicine, National Cheng Kung University Hospital, 138, Sheng Li Road, Tainan, 70403, Taiwan, ROC; Tel: +886-6-2353535 ext 5355; Fax: +8866-2386650; E-mail: [email protected] SLEEP, Vol. 37, No. 8, 2014
validated and reproducible.16,17 Although the gold standard is measuring central arterial stiffness via carotid-femoral PWV (cfPWV), this requires persistent lateral rotation of the patient’s neck and exposure of the inguinal region. In contrast, brachialankle PWV (baPWV) is more convenient to measure, because a pressure cuff only needs to be wrapped over the limbs while the subject is in a supine position. Studies also indicate that baPWV has a similar degree of association with cardiovascular risk factors and clinical events as cfPWV.10,18–22 To date, few studies have examined the relationship between sleep duration and arterial stiffness. Only one cross-sectional Japanese study revealed a positive association between longer sleep duration and increased arterial stiffness, as measured by baPWV, in males, but not females.23 However, their study subjects were confined to middle-aged (35–62 y) civil servants, without consideration of younger and older subjects. The aim of this study is thus to examine the association between arterial stiffness and sleep duration in a Taiwanese population. METHODS The baseline data, including 7,565 adult examinees, were collected from a health examination center in National Cheng Kung University Hospital, a tertiary medical center in Tainan, Taiwan, from October 2006 to August 2009. All subjects completed a structured questionnaire, which included items to collect their demographic information, medical history, medication history, lifestyle habits (cigarette smoking, alcohol drinking, and regular exercise), and self-reported sleep duration and snoring frequency. After exclusion of individuals with
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a history of cerebrovascular events, coronary artery disease, peripheral artery disease with an ankle-brachial index (ABI) less than 0.9, those taking lipid-lowering drugs, antihypertensive drugs, hypoglycemic agents, or anti-inflammatory drugs, and incomplete data, a total of 3,508 subjects were enrolled for the final analysis. Cigarette smoking was classified as current smoker (at least one pack per month for at least the previous 6 mo) and noncurrent smoker. Alcohol drinking was classified as current drinker (at least once per week for at least the previous 6 mo) and noncurrent drinker. Regular exercise was defined as vigorous exercise at least three times per week. Sleep duration was assessed by the following question in the self-reported questionnaire: “On average, how many hours and minutes do you sleep per night?” We further classified sleep duration into three groups: short (< 6 h), normal (6–8 h), and long (> 8 h).24 Anthropometric measurements included body weight (minimal unit of measurement: 0.1 kg) and height (minimal unit of measurement: 0.1 cm). Body mass index (BMI) was calculated as weight (kg)/height (m2). Blood pressure (BP) was measured in a supine position with a BP monitor (1846SX; Johnson and Johnson, assembled in Mexico) after at least 15 min of rest. Hypertension was defined as systolic BP greater than 140 mmHg or diastolic BP greater than 90 mmHg. After 10 h of overnight fasting, all subjects underwent the following blood tests: fasting plasma glucose, hemoglobin (Hb)A1C, 2-h postload plasma glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride, and creatinine. Diabetes mellitus was defined as a fasting glucose level of 126 mg/dL or more, or a 2-h postload glucose level of 200 mg/dL or more, or HbA1C more than or equal to 6.5%. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. An increased atherosclerosis risk was defined as a TC/ HDL-C ratio of more than 5. Arterial stiffness was measured by baPWV, using a noninvasive vascular screening device (BP-203RPE II; Colin Medical Technology, Komaki, Japan) with four pneumatic pressure cuffs over bilateral brachial arteries and tibial arteries, after 5 min of rest in the supine position. Heart rate and ABI were measured concurrently with PWV measurement. The baPWV value was calculated as the distance traveled by the pulse wave divided by the time taken to travel this distance. Increased arterial stiffness was defined as baPWV ≥ 1400 cm/sec. Statistical Analysis All statistical analyses were performed using the 17th version of the SPSS (Chicago, IL) software. The subjects were classified into those with and without increased arterial stiffness. Clinical characteristics in the study are presented as means ± standard deviation (SD) or percentage. χ2 tests were used to compare the categorical variables between groups. In addition, the comparisons of the continuous variables were analyzed using Student’s t-test between groups. Analysis of covariance (ANCOVA) was used to compare the baPWV values among subjects with different sleep durations by sex. Finally, we used multiple logistic regressions to explore the relationship between sleep duration and arterial stiffness. Statistical significance was defined as P < 0.05. SLEEP, Vol. 37, No. 8, 2014
RESULTS Table 1 shows the comparisons of clinical characteristics between subjects with and without increased baPWV by sex. In both sexes, subjects with increased arterial stiffness were older; had a higher systolic and diastolic blood pressure, fasting plasma glucose, total cholesterol, TC/HDL-C ratio, and prevalences of hypertension and diabetes mellitus; and lower eGFR than those without increased arterial stiffness. In addition, BMI, triglycerides, HDL-C, and alcohol drinking were significantly different between female subjects with and without increased arterial stiffness. However, the sleep duration was different between subjects with and without increased arterial stiffness in males only. In males, based on ANCOVA, Figure 1 showed that long sleepers had a higher baPWV value than normal sleepers (adjusted mean: 1413.6 ± 17.8 versus 1348.9 ± 4.2 cm/ sec, P < 0.001). There was no significant difference in baPWV between short and normal sleepers (adjusted mean: 1342.2 ± 10.3 versus 1348.9 ± 4.2 cm/sec, P = 0.547). As for females, the baPWV values in normal, short, and long sleepers were 1266.0 ± 5.1, 1275.0 ± 11.8, and 1297.3 ± 19.7cm/sec, respectively. There were no significant differences in baPWV among these three groups. The results of the multiple logistic regression analysis on the relationship between sleep duration and baPWV in males and females are summarized in Table 2. In males, long sleepers (OR = 1.75, 95% confidence interval [CI] = 1.04–2.94), but not short sleepers (OR = 0.98, 95% CI = 0.72–1.35), had a higher risk of increased arterial stiffness after adjusting for other variables. In addition, age of 40–59 y versus younger than 40 y, age 60 y or older versus younger than 40 y, lower eGFR, hypertension, diabetes, TC/HDL-C ratio > 5, and cigarette smoking were independently associated with increased arterial stiffness, and regular exercise had an inverted relationship. In females, although age 40–59 y versus younger than 40 y, age 60 y or older versus younger than 40 y, BMI, hypertension and TC/ HDL-C ratio were the independently associated factors, both short and long sleep duration were not related to increased arterial stiffness. DISCUSSION Our results revealed that long sleep duration is associated with a higher risk of increased arterial stiffness in males, whereas no significant association was found for short sleepers of either sex, after adjusting for the potential confounding factors in a Taiwanese population. To the best of our knowledge, there has only been one cross-sectional study on the relationship between sleep duration and arterial stiffness as measured by baPWV.23 However, the study subjects in that study were mainly males, and confined to middle-aged Japanese civil servants. In addition, subjects with medications that would influence arterial stiffness were not excluded. In contrast, our study excluded subjects taking lipid-lowering drugs, antihypertensive agents, hypoglycemic agents, and anti-inflammatory drugs because previous research showed that arterial stiffness is mainly caused by an inflammatory process,15 and that a variety of pharmacological treatments are associated with changes in arterial stiffness.25 The results of the logistic regression analyses carried out in this work showed that only long sleep duration was associated
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Table 1—Clinical characteristics of study subjects with and without increased arterial stiffness by sex baPWV in Males
Age (y) Age group (y) < 40 40–59 ≥ 60 Body mass index (kg/m2) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Creatinine (mg/dL) eGFR (ml/min/1.73 m2) Fasting plasma glucose (mg/dL) Total cholesterol (mg/dL) Triglyceride (mg/dL) HDL-C (mg/dL) TC/HDL-C > 5 Sleep duration (hours) 8 Snoring ≥ 3/w Hypertension Diabetes mellitus Smoking Alcohol drinking Regular exercise ≥ 3/w
P value
< 1400cm/s (n = 1,418) 42.3 ± 9.6
≥ 1400 cm/s (n = 677) 52.7 ± 11.1
547 (38.6) 823 (58.0) 48 (3.4) 24.7 ± 3.3 115.9 ± 10.3 69.7 ± 8.3 0.96 ± 0.12 93.3 ± 15.1 88.6 ± 18.8 195.1 ± 35.8 136.5 ± 94.3 47.0 ± 11.5 377 (26.6)
75 (11.1) 433 (64.0) 169 (25.0) 24.8 ± 3.1 130.1 ± 15.5 79.6 ± 10.4 0.99 ± 0.35 88.1 ± 16.0 94.9 ± 24.6 204.3 ± 36.6 144.1 ± 93.0 47.0 ± 12.1 227 (33.5)
188 (13.3) 1184 (83.5) 46 (3.2) 352 (24.6) 60 (4.2) 54 (3.8) 325 (22.9) 365 (25.7) 209 (14.7)
94 (13.9) 532 (78.6) 51 (7.5) 175 (24.4) 213 (31.5) 88 (13.0) 172 (25.4) 175 (25.8) 84 (12.4)
< 0.001 < 0.001
0.216 < 0.001 < 0.001 0.009 < 0.001 < 0.001 < 0.001 0.085 0.957 0.001 < 0.001
0.978 < 0.001 < 0.001 0.211 0.958 0.150
baPWV in Females < 1400cm/s (n = 1,094) 42.3 ± 9.7
≥ 1400 cm/s (n = 319) 55.9 ± 9.4
423 (38.7) 635 (58.0) 36 (3.3) 22.2 ± 3.3 106.1 ± 11.0 61.7 ± 8.0 0.69 ± 0.19 102.4 ± 18.3 85.1 ± 12.3 189.9 ± 34.3 89.5 ± 53.4 60.1 ± 14.3 53 (4.8)
12 (3.8) 208 (65.2) 99 (31.0) 23.8 ± 3.3 128.6 ± 16.5 73.9 ± 10.0 0.73 ± 0.38 94.6 ± 20.0 93.6 ± 27.4 206.8 ± 41.3 124.3 ± 84.6 57.3 ± 14.6 48 (15.0)
165 (15.1) 876 (80.1) 53 (4.8) 102 (9.3) 16 (1.5) 29 (2.7) 35 (3.2) 53 (4.8) 99 (9.0)
45 (14.1) 250 (74.4) 24 (7.5) 39 (11.5) 96 (30.1) 39 (12.2) 4 (1.3) 4 (1.3) 33 (10.3)
P value
< 0.001 < 0.001
< 0.001 < 0.001 < 0.001 0.150 < 0.001 < 0.001 < 0.001 < 0.001 0.002 < 0.001 0.174
0.354 < 0.001 < 0.001 0.062 0.004 0.484
Data are expressed as means ± standard deviation or numbers (percentage). baPWV, brachial-ankle pulse-wave velocity; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein-cholesterol; TC, total cholesterol.
with a higher risk of increased arterial stiffness in male, but not in females. This is consistent with the study results from Yoshioka et al., who found that, compared with a reference group that reported an average of 7 h of sleep, long sleep duration was significantly associated with higher baPWV.23 The underlying mechanisms between long sleep duration and arterial stiffness are not clear, but the relationship may be related to the following factors: sleep fragmentation, fatigue, immune function, photoperiodic abnormalities, lack of challenge, depression, and underlying disease processes such as sleep apnea, heart disease, and failing health,24 which might suggest that long sleep is more strongly associated with cardiovascular outcomes and all-cause mortality than short sleep.1,3,26 In addition, inflammatory pathways may be another mechanism for the positive relationship between long sleep duration and increased arterial stiffness. Because Asian long sleepers had a higher inflammation status than short sleepers,27,28 the inflammatory process will cause dysregulation of collagen and elastin fibers of the vascular wall, leading to arterial stiffness.15 Furthermore, long sleepers reported difficulty falling asleep, awakening during the night, awakening too early, awakening unrefreshed, daytime sleepiness,29 and greater insomnia and sleeping pill use30 than normal sleepers. Thus, long sleep duration may be related to poor sleep SLEEP, Vol. 37, No. 8, 2014
quality, and poor sleep quality was found to be associated with insulin resistance,31 alteration of hypothalamic-pituitaryadrenal system activity,32 increased sympathetic activity,33 and endothelial function impairment.34,35 This may partially explain the association between long sleep duration and increased arterial stiffness. Further research is needed to explore their mechanism. With regard to sex differences in the risk of increased arterial stiffness, earlier studies revealed a linear relationship between CRP and PWV among late perimenopausal or postmenopausal women,36 and that the values of central pulse pressure and PWV were lower in hormone therapy users.37,38 These findings show that the female hormone may be a protective factor for arterial stiffness, and thus may account for the sex advantage found among females in this context. Both structural and functional changes in the arteries occur with the aging process. Sympathetic nerve activity elevation,39 endothelial dysfunction,40 and proinflammatory status41 induce vasoconstriction, smooth muscle cell hypertrophy, and elastin fragmentation with collagen synthesis, and then may lead to increased arterial stiffness with aging.42 Our study showed that hypertension and a TC/HDL-C ratio greater than 5 were independently associated factors of increased
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baPWV (cm/s)
baPWV (cm/s)
arterial stiffness, consistent with previous findings.43–45 Higher blood pressure increases the shearing stress of the artery, which Male Female induces arterial stiffening through endothelial dysfunction,43 P < 0.001 alterations in the extracellular matrix,44 and activation of the 1440 renin-angiotensin-aldosterone system.45 According to previous 1420 studies, the TC/HDL-C ratio is a superior measure of risk for 1400 P = 0.547 coronary heart disease compared with either TC or low-density 1380 lipoprotein cholesterol (LDL-C) levels.46,47 In addition, the 1360 cutoff point of five shows higher specificity and accuracy in 1340 Chinese populations when compared with using a LDL-C level 1320 of 130 mg/dL as the cutoff point.48 Dyslipidemia also has been 1300 shown to have a harmful effect on arterial stiffness through the 1280 mechanisms of endothelial dysfunction, reduced nitric oxide 8 bioavailability, and the inflammatory process.49 Sleep Duration (hours) Diabetes was found to be associated with increased arterial stiffness,50–52 and the mechanism underlying this may be related P = 0.124 to the inflammatory process and increased oxidative stress.50 In 1330 addition, advanced glycation end-products link with collagen 1320 in the vascular wall, resulting in irreversible cross-links, which 1310 P = 0.483 1300 are stiffer and less susceptible to hydrolytic turnover, and this 1290 leads to an increase in arterial stiffness.53 The only significant 1280 association found between diabetes and increased arterial 1270 stiffness in the current study was among males. This may be 1260 related to the lower statistical power with regard to the females’ 1250 data, because there was a lower prevalence of diabetes among 1240 women (4.8%) than men (6.8%) in this work. 1230 8 Our results showed that a higher BMI was positively related Sleep Duration (hours) to increased arterial stiffness in females only. The relationship between BMI and arterial stiffness remains unclear. Some Figure 1—Comparisons of brachial-ankle pulse-wave velocity studies show a positive association between BMI and aortic (baPWV) among subjects with different sleep durations by sex based PWV,54,55 whereas others find an inverse association between on analysis of covariance. BMI and baPWV in both sexes.56,57 Moreover, Rodrigues et al. found that BMI is not independently associated with increased aortic stiffness.58 The effects of BMI on arterial stiffness might be mediated by the intermediate parameters of Table 2—The adjusted odds ratios and 95% confidence intervals of multiple logistic regression analysis for cardiovascular risk factors. There was the relationship between sleep duration and increased arterial stiffness by sex a high correlation between BMI and Male Female TC/HDL-C ratio (r = 0.458) in current OR (95% CI) P value OR (95% CI) P value study. In addition, the high correlation Age group (y) coefficient exists between baPWV 40–59 vs. < 40 3.65 (2.70–4.92) < 0.001 7.78 (4.21–14.37) < 0.001 and the following variables: age ≥ 60 vs. < 40 21.67 (13.85–33.91) < 0.001 48.08 (23.16–99.85) < 0.001 (r = 0.592) and systolic (r = 0.668) and 0.98 (0.94–1.02) 0.237 1.06 (1.01–1.16) 0.011 Body mass index (kg/m2) diastolic blood pressures (r = 0.598). 0.99 (0.98–1.00) 0.040 0.99 (0.99–1.00) 0.204 eGFR (mL/min/1.73 m2) The effect of BMI on arterial stiffness Hypertension (yes vs. no) 10.40 (7.39–14.64) < 0.001 14.84 (8.20–26.87) < 0.001 might be caused by high collinearity Diabetes mellitus (yes vs. no) 2.36 (1.55–3.58) < 0.001 1.10 (0.56–2.15) 0.781 and mediated by age, blood pressure, and TC/HDL-C ratio. This may be a TC/HDL-C > 5 (yes vs. no) 1.39 (1.08–1.77) 0.009 2.12 (1.27–3.55) 0.004 partial explanation for the inconsisSleep duration (h) tent results in these earlier studies. < 6 vs. 6–8 0.98 (0.72–1.35) 0.920 0.86 (0.56–1.31) 0.476 Our study showed an inverse asso> 8 vs. 6–8 1.75 (1.04–2.94) 0.034 1.02 (0.48–2.15) 0.963 ciation between eGFR and increased Smoking (yes vs. no) 1.44 (1.11–1.87) 0.007 0.45 (0.13–1.62) 0.224 arterial stiffness in males. Chronic Alcohol drinking (yes vs. no) 0.95 (0.74–1.23) 0.700 0.40 (0.13–1.17) 0.092 kidney disease is associated with Regular exercise (yes vs. no) 0.69 (0.50–0.95) 0.025 1.09 (0.68–1.77) 0.717 increased arterial stiffness through the Snoring ≥ 3/week (yes vs. no) 0.95 (0.73–1.22) 0.670 0.89 (0.52–1.52) 0.676 mechanism of endothelial dysfunction, chronic inflammation and CI, confidence interval; eGFR, estimated glomerular filtration rate, HDL-C, high-density lipoproteinvascular calcification, and activation cholesterol; OR, odds ratio; TC, total cholesterol. of the renin-angiotensin-aldosterone SLEEP, Vol. 37, No. 8, 2014
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system.59,60 As for the influence of lifestyle status on arterial stiffness, smoking has been shown to be positively related to increased arterial stiffness,61 whereas regular aerobic exercise is associated with reduced arterial stiffness.62 In our study, there was only a significant association between lifestyle status and increased arterial stiffness in males. This may be explained by the lower number of female subjects who smoked and who exercised less regularly than male subjects. This study has several limitations, as follows. First, the cross-sectional design of this work means that it is not possible to establish a causal relationship between sleep duration and arterial stiffness. Second, self-reported sleep duration may have subjective errors, although Lauderdale et al. found that subjective estimates of sleep duration correlated highly with polysomnographic assessments.63 Third, we measured only the quantity but not the quality of sleep, although poor sleep quality scores on the Pittsburgh Sleep Quality Index have been found to be significantly related to various cardiovascular risk factors, such as diabetes and hypertension.64,65 Fourth, subjects with obstructive sleep apnea syndrome were not excluded in our study, and this condition has been found to be associated with increased arterial stiffness.66 Although we adjusted for the multiple confounding variables and snoring frequency, the effect of obstructive sleep apnea may not have been fully controlled for. In conclusion, long sleep duration was associated with a higher risk of increased arterial stiffness in males. Short sleepers did not exhibit a significant risk of increased arterial stiffness in either sex. In addition to cardiovascular risk factors and lifestyle, the results of this study show that sleep duration cannot be ignored when considering the prevention of cardiovascular disease. ABBREVIATIONS ABI, ankle-brachial index baPWV, brachial-ankle PWV BMI, body mass index BP, blood pressure cfPWV, carotid-femoral PWV eGFR, estimated glomerular filtration rate HDL-C, high density lipoprotein cholesterol LDL-C, low density lipoprotein cholesterol MDRD, Modification of Diet in Renal Disease PWV, pulse-wave velocity TC, total cholesterol DISCLOSURE STATEMENT This was not an industry supported study. This work was supported by the Department of Family Medicine, National Cheng-Kung University Hospital [Grant number NCKUHFM101-002]. The authors have indicated no financial conflicts of interest. REFERENCES
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