Soluble CD14 Levels in the Jackson Heart Study: Associations With Cardiovascular Disease Risk and Genetic Variants

Objective: sCD14 (soluble CD14) is a circulating pattern recognition receptor involved in inflammatory signaling. Although it is known that sCD14 levels vary by race, information on the genetic and cardiovascular disease (CVD) risk relationships of sCD14 in Black participants is limited. Approach and Results: We measured sCD14 in plasma at the baseline exam from n=3492 Black participants from the JHS (Jackson Heart Study). We evaluated associations between sCD14 and subclinical CVD measures, incident CVD events, and mortality under 3 levels of covariate adjustment. We used whole-genome sequence data from the Trans-Omics for Personalized Medicine program to identify genetic associations with sCD14. Adjusting for CVD risk factors and C-reactive protein, higher sCD14 was significantly associated with increased risk of mortality (hazard ratio, 1.25 [95% CI, 1.17–1.32]), incident coronary heart disease (hazard ratio, 1.28 [95% CI, 1.11–1.47]), and incident heart failure (hazard ratio, 1.27 [95% CI, 1.15–1.41]), but not stroke (hazard ratio, 0.96 [95% CI, 0.84–1.09]). Some of these relationships differed by age or sex: the association between sCD14 and heart failure was only observed in females; there was an association between sCD14 and stroke only at younger ages (in the lowest tertile of age, <49.4 years). We replicated the association between sCD14 levels with African ancestry-specific allele (rs75652866) on the CD14 region of chromosome 5q31. We additionally identified 2 novel statistically distinct genetic associations with sCD14 represented by index variants rs770147646 and rs57599368, also in the chromosome 5q31 region. Conclusions: sCD14 independently predicts CVD-related outcomes and mortality in Black participants.

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Abstract P107: Leucocyte Telomere Length and Cardiovascular Disease in the Jackson Heart Study

Circulation ◽

10.1161/circ.135.suppl_1.p107 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Stanford Mwasongwe ◽

Laura Raffield ◽

Yan Gao ◽

James G Wilson ◽

Abraham Aviv ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Telomere Length ◽

Left Ventricular ◽

Jackson Heart Study ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Heart Study ◽

Increased Risk ◽

Age And Sex

Background: In European descent populations, shorter leucocyte telomere length (LTL) has been associated with clinical and subclinical atherosclerosis, while longer LTL has been associated with greater left ventricular hypertrophy (LVH). We evaluated the relationship of LTL with subclinical indices of cardiovascular disease (CVD) (coronary artery calcification [CAC], abdominal aorta calcification [AAC], carotid intima media thickness [CIMT], left ventricular mass [LVM], and ankle-brachial index [ABI]) in African Americans (AAs). We also examined whether LTL is associated with CVD events and mortality. Methods: Analyses included participants of the Jackson Heart Study (JHS), a prospective cohort study of AAs, with LTL data (n=2,573) measured by Southern blot analysis in DNA from the baseline exam (2000-2004). Adjudicated CVD events (coronary heart disease [CHD], heart failure [HF] and stroke) and mortality were identified through December 2012. Relationships were assessed using linear, logistic regression models, or Tobit model (CAC and AAC due to left censoring) in STATA 14. Results: In an age and sex adjusted model, longer LTL was significantly associated with lower CAC ( P =0.049, β=-0.535; 95% confidence interval [CI], -1.066,-0.003); this association was no longer significant after adjusting for body mass index, current smoking and other CVD risk factors. There were no significant associations between LTL and AAC, CIMT, or LVM. LTL was associated with higher ABI ( P =0.017, β=0.023; 95% CI, 0.004, 0.042) when the highest was compared to the lowest LTL quartile in models adjusted for CVD risk factors. After a median follow-up of 9 years, longer LTL was associated with lower risk of incident ischemic stroke and total mortality in age and sex adjusted models, but these associations were no longer significant in models fully adjusted for CVD risk factors. Conclusions: In conclusion, among a community-based cohort of AAs, LTL was associated with increased ABI, indicative of increased risk of peripheral arterial disease, but there were no significant associations with other CVD indices and mortality after adjustment for established risk factors.

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Goal‐Striving Stress and Incident Cardiovascular Disease in Blacks: The Jackson Heart Study

Journal of the American Heart Association ◽

10.1161/jaha.119.015707 ◽

2020 ◽

Vol 9 (9) ◽

Cited By ~ 2

Author(s):

LáShauntá M. Glover ◽

Loretta R. Cain‐Shields ◽

Tanya M. Spruill ◽

Emily C. O'Brien ◽

Sharrelle Barber ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Jackson Heart Study ◽

Goal Striving ◽

Hazard Ratios ◽

Heart Study ◽

Increased Risk ◽

Unit Increase

Background Goal‐striving stress (GSS), the stress from striving for goals, is associated with poor health. Less is known about its association with cardiovascular disease (CVD). Methods and Results We used data from the JHS (Jackson Heart Study), a study of CVD among blacks (21–95 years old) from 2000 to 2015. Participants free of CVD at baseline (2000–2004) were included in this analysis (n=4648). GSS was examined in categories (low, moderate, high) and in SD units. Incident CVD was defined as fatal or nonfatal stroke, coronary heart disease (CHD), and/or heart failure. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD by levels of GSS, adjusting for demographics, socioeconomic status, health behaviors, risk factors, and perceived stress. The distribution of GSS categories was as follows: 40.77% low, 33.97% moderate, and 25.26% high. Over an average of 12 years, there were 140 incident stroke events, 164 CHD events, and 194 heart failure events. After full adjustment, high (versus low) GSS was associated with a lower risk of stroke (HR, 0.38; 95% CI, 0.17–0.83) and a higher risk of CHD (HR, 1.91; 95% CI, 1.10–3.33) among women. A 1‐standard deviation unit increase in GSS was associated with a 31% increased risk of CHD (HR, 1.31; 95% CI, 1.10–1.56) among women. Conclusions Higher GSS may be a risk factor for developing CHD among women; however, it appears to be protective of stroke among women. These analyses should be replicated in other samples of black individuals.

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Abstract P253: Proton Pump Inhibitor Use is Positively Associated with Incidence of Cardiovascular Disease

Circulation ◽

10.1161/circ.135.suppl_1.p253 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Elizabeth J Bell ◽

Jennifer L St. Sauver ◽

Veronique L Roger ◽

Nicholas B Larson ◽

Hongfang Liu ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Coronary Heart Disease ◽

Heart Disease ◽

Language Processing ◽

Proton Pump ◽

Hazard Ratio ◽

Time Varying ◽

Increased Risk ◽

The Impact

Introduction: Proton pump inhibitors (PPIs) are used by an estimated 29 million Americans. PPIs increase the levels of asymmetrical dimethylarginine, a known risk factor for cardiovascular disease (CVD). Data from a select population of patients with CVD suggest that PPI use is associated with an increased risk of stroke, heart failure, and coronary heart disease. The impact of PPI use on incident CVD is largely unknown in the general population. Hypothesis: We hypothesized that PPI users have a higher risk of incident total CVD, coronary heart disease, stroke, and heart failure compared to nonusers. To demonstrate specificity of association, we additionally hypothesized that there is not an association between use of H 2 -blockers - another commonly used class of medications with similar indications as PPIs - and CVD. Methods: We used the Rochester Epidemiology Project’s medical records-linkage system to identify all residents of Olmsted County, MN on our baseline date of January 1, 2004 (N=140217). We excluded persons who did not grant permission for their records to be used for research, were <18 years old, had a history of CVD, had missing data for any variable included in our model, or had evidence of PPI use within the previous year.We followed our final cohort (N=58175) for up to 12 years. The administrative censoring date for CVD was 1/20/2014, for coronary heart disease was 8/3/2016, for stroke was 9/9/2016, and for heart failure was 1/20/2014. Time-varying PPI ever-use was ascertained using 1) natural language processing to capture unstructured text from the electronic health record, and 2) outpatient prescriptions. An incident CVD event was defined as the first occurrence of 1) validated heart failure, 2) validated coronary heart disease, or 3) stroke, defined using diagnostic codes only. As a secondary analysis, we calculated the association between time-varying H 2 -blocker ever-use and CVD among persons not using H 2 -blockers at baseline. Results: After adjustment for age, sex, race, education, hypertension, hyperlipidemia, diabetes, and body-mass-index, PPI use was associated with an approximately 50% higher risk of CVD (hazard ratio [95% CI]: 1.51 [1.37-1.67]; 2187 CVD events), stroke (hazard ratio [95% CI]: 1.49 [1.35-1.65]; 1928 stroke events), and heart failure (hazard ratio [95% CI]: 1.56 [1.23-1.97]; 353 heart failure events) compared to nonusers. Users of PPIs had a 35% greater risk of coronary heart disease than nonusers (95% CI: 1.13-1.61; 626 coronary heart disease events). Use of H 2 -blockers was also associated with a higher risk of CVD (adjusted hazard ratio [95% CI]: 1.23 [1.08-1.41]; 2331 CVD events). Conclusions: PPI use is associated with a higher risk of CVD, coronary heart disease, stroke and heart failure. Use of a drug with no known cardiac toxicity - H 2 -blockers - was also associated with a greater risk of CVD, warranting further study.

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Aortic Root Diameter and Arterial Stiffness: Conjoint Relations to the Incidence of Cardiovascular Disease in the Framingham Heart Study

Hypertension ◽

10.1161/hypertensionaha.121.17702 ◽

2021 ◽

Author(s):

Ramachandran S. Vasan ◽

Rebecca J. Song ◽

Vanessa Xanthakis ◽

Gary F. Mitchell

Keyword(s):

Cardiovascular Disease ◽

Pulse Pressure ◽

Aortic Root ◽

Cox Regression ◽

Prognostic Significance ◽

Root Diameter ◽

Cvd Risk ◽

Heart Study ◽

Increased Risk ◽

Central Pulse Pressure

Higher central pulse pressure is associated with higher carotid-femoral pulse wave velocity (CFPWV) and an increased risk of cardiovascular disease (CVD). A smaller aortic root diameter (AoR) is associated with higher central pulse pressure. We hypothesized that the combination of a smaller AoR and higher CFPWV is associated with increased CVD risk (relative to a larger AoR and lower CFPWV). We tested this hypothesis in the community-based Framingham Study (N=1970, mean age 60 years, 57% women). We created sex-specific longitudinal echocardiographic AoR trajectories over 2 decades, categorizing participants into smaller versus larger AoR groups. We cross-classified participants based on their AoR trajectory and CFPWV (dichotomized at the sex-specific median). We used Cox regression to relate the cross-classified groups to CVD incidence on follow-up (median 17 years): lower CFPWV, larger AoR (referent group; 6.4/1000 person-years); lower CFPWV, smaller AoR (6.9/1000 person-years); higher CFPWV, larger AoR (23.1/1000 person-years); and higher CFPWV, smaller AoR (21.9/1000 person-years). In sex-pooled analyses, groups with higher CFPWV were associated with a multivariable-adjusted 1.8-fold risk of CVD ( P <0.01) regardless of AoR size. We observed effect modification by sex ( P for sex×AoR-CFPWV group interaction 0.04). In men, the group with smaller AoR and higher CFPWV was associated with a 2.5- to 2.8-fold risk of CVD ( P <0.001). In women, the group with larger AoR and higher CFPWV experienced a statistically nonsignificant 70% to 80% higher CVD risk. Our observations indicate that the prognostic significance of a smaller versus larger AoR varies in men versus women. Additional studies are warranted to confirm our findings.

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Abstract MP65: Masked Hypertension is Associated with Cardiovascular Disease Events in African Americans: The Jackson Heart Study

Circulation ◽

10.1161/circ.133.suppl_1.mp65 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

John N Booth ◽

Keith M Diaz ◽

Samantha Seals ◽

Mario Sims ◽

Joseph Ravenell ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

African Americans ◽

Blood Pressure Monitoring ◽

Masked Hypertension ◽

Jackson Heart Study ◽

Cvd Risk ◽

Nocturnal Hypertension ◽

Heart Study ◽

All Cause Mortality

Introduction: Masked hypertension has been associated with increased cardiovascular disease (CVD) risk in Europeans and Asians. Hypothesis: Determine the association of masked hypertension with CVD events and all-cause mortality in African Americans (AA). Methods: The Jackson Heart Study, an exclusively AA population-based, prospective cohort study, was restricted to participants with clinic systolic/diastolic blood pressure (SBP/DBP) < 140/90 mmHg and valid ambulatory blood pressure monitoring (ABPM) at the baseline exam in 2000-2004 (n=738). Masked daytime hypertension was defined as mean ambulatory daytime (10am-8pm) SBP ≥ 135 mmHg or DBP ≥ 85 mmHg. Masked nocturnal hypertension was defined as mean ambulatory nighttime (12am-6am) SBP ≥ 120 mmHg or DBP ≥ 70 mmHg. Using all ABPM measurements, masked 24-hour hypertension was defined as mean SBP ≥ 130 mmHg or DBP ≥ 80 mmHg. CVD events (nonfatal/fatal stroke, nonfatal myocardial infarction or fatal coronary heart disease) and all-cause mortality were identified and adjudicated through December 31, 2011. Results: Any masked hypertension (masked daytime, nocturnal or 24-hour hypertension) was present in 52.2% of participants; 28.2% had masked daytime hypertension, 48.2% had masked nocturnal hypertension and 31.7% had masked 24-hour hypertension. There were 51 CVD events and 44 deaths over a median follow up of 8.2 and 8.5 years, respectively. The CVD rate (95% CI) per 1,000 person years in participants with and without any masked hypertension were 13.5 (9.9-18.4) and 3.9 (2.2-7.1), respectively (Table). The multivariable adjusted hazard ratio (95% CI) between any masked hypertension and CVD was 2.49 (1.26-4.93). CVD rates for those with and without masked daytime, nocturnal and 24-hour hypertension, and the hazard ratios for CVD associated with masked daytime, nocturnal and 24-hour hypertension, were similar. Masked hypertension was not associated with all-cause mortality. Conclusion: Masked hypertension is common and associated with increased CVD risk in AAs.

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Abstract P345: Prediction of Cardiovascular Disease Events and Death using Multiple Biomarkers in African Americans: the Jackson Heart Study

Circulation ◽

10.1161/circ.129.suppl_1.p345 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Solomon K Musani ◽

Ramachandran Vasan ◽

Aurelian Bidulescu ◽

Jung Lee ◽

Gregory Wilson ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

African Americans ◽

High Sensitivity ◽

Serum Cortisol ◽

Jackson Heart Study ◽

Cvd Risk ◽

Risk Reclassification ◽

Heart Study ◽

Traditional Risk Factors

Background: The usefulness of biomarkers from different biologic pathways for predicting cardiovascular disease (CVD) events among African Americans is not well understood. Methods: We evaluated prospectively 3,102 Jackson Heart Study participants (mean age 54 years; 64% women) with data on a panel of 9 biomarkers representing inflammation (high sensitivity C - reactive protein), adiposity (adiponectin, leptin), neurohormonal activation (B-type natriuretic peptide [BNP], aldosterone, and cortisol); insulin resistance (HOMA-IR); and endothelial function (endothelin and homocysteine). We used Cox proportional hazard regression to relate the biomarker panel to the incidence of CVD (stroke, coronary heart disease, angina, heart failure and intermittent claudication) adjusting for standard CVD risk factors. Results: On follow-up (median 8.2 years), 224 participants (141 women) experienced a first CVD event, and 238 (140 women) died. Circulating concentrations of aldosterone, BNP and HOMA-IR were associated with CVD (multivariable-adjusted hazard ratios [HR] and 95% confidence interval [CI] per standard deviation (SD) increase in log-biomarker) were, respectively 1.15, (95% CI 1.01-1.30, p=0.016), 1.97, (95% CI 1.22-2.41, p<0.0001), and 1.30, (95% CI 1.10-1.52, p=0.0064). Blood cortisol and homocysteine were associated with death (HR per SD increment log-biomarker, respectively, 1.17, (95% CI 1.01-1.35, p=0.042), and 1.24, (95% CI 1.10-1.40, pvalue=0.0005). Biomarkers improved risk reclassification by 0.135; 0.120 of which was gained in classification of participants that experienced CVD events and 0.015 from participants that did not. Also, biomarkers marginally increased the model c-statistic beyond traditional risk factors. Conclusions: In our community-based sample of African Americans, circulating aldosterone, BNP and HOMA-IR predicted CVD risk, whereas serum cortisol and homocysteine predicted death. However, the incremental yield of biomarkers over traditional risk factors for risk prediction was minimal.

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Psychosocial determinants of cardiovascular events among black Americans with chronic kidney disease or associated risk factors in the Jackson heart study

BMC Nephrology ◽

10.1186/s12882-021-02594-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Nrupen A. Bhavsar ◽

Clemontina A. Davenport ◽

Lexie Zidanyue Yang ◽

Sarah Peskoe ◽

Julia J. Scialla ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Psychosocial Factors ◽

Principal Component ◽

Coping Resources ◽

Jackson Heart Study ◽

Cvd Risk ◽

Heart Study ◽

Increased Risk

Abstract Background Individuals with chronic kidney disease (CKD), hypertension (HTN), or diabetes mellitus (DM) are at increased risk for cardiovascular disease (CVD). The extent to which psychosocial factors are associated with increased CVD risk within these individuals is unclear. Black individuals experience a high degree of psychosocial stressors due to socioeconomic factors, environment, racism, and discrimination. We examined the association between psychosocial factors and risk of CVD events among Black men and women with CKD and CKD risk factors in the Jackson Heart Study. Methods and Results We identified 1919 participants with prevalent CKD or CKD risk factors at baseline. We used rotated principal component analysis - a form of unsupervised machine learning that may identify constructs not intuitively identified by a person - to describe five groups of psychosocial components (including negative moods, religiosity, discrimination, negative outlooks, and negative coping resources) based on a battery of questionnaires. Multiple imputation by chained equation (MICE) was used to impute missing covariate data. Cox models were used to quantify the association between psychosocial components and incident CVD, defined as a fatal coronary heart disease event, myocardial infarction, cardiac procedure (angiography or revascularization procedure), or stroke. Of the 929 participants in the analysis, 67% were female, 28% were current/former smokers with mean age of 56 years and mean BMI of 33 kg/m2. Over a median follow-up of 8 years, 6% had an incident CVD event. In multivariable models, each standard deviation (SD) increase in the religiosity component was associated with an increased hazard for CVD event (hazard ratio [HR] = 1.52, 95% CI: 1.09–2.13). Conclusions Religiosity was associated with CVD among participants with prevalent CKD or CKD risk factors. Studies to better understand the mechanisms of this relationship are needed.

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Abstract P172: Associations of Body Mass Index From Early-, Mid-, and Older- Adulthood With Incident Heart Failure and Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

Circulation ◽

10.1161/circ.137.suppl_1.p172 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Michael J Fliotsos ◽

Di Zhao ◽

Chiadi Ndumele ◽

Eliseo Guallar ◽

Gregory L Burke ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Older Adults ◽

Body Mass Index ◽

Body Mass ◽

Clinical Encounter ◽

Cvd Risk ◽

Prognostic Information ◽

Measured Weight ◽

Increased Risk

Background: Obesity contributes significantly to increased risk of cardiovascular disease (CVD) and particularly heart failure (HF). However, an elevated body mass index (BMI) in older adults might not fully reflect the additional risk associated with excess weight at a younger age. We determined the prognostic value of self-reported weights from early- and mid-adulthood, after accounting for current weight, with incident HF and CVD. Methods: We studied 6,437 MESA participants (aged 45-84 years) with self-reported weights at ages 20 and 40 (by questionnaire) and measured weight at the baseline exam (2000-2002). BMI was calculated using measured height at baseline. Cox hazard models assessed relationships between BMI at each age with HF and CVD. Results: Participant mean age was 62±10 years and 53% were women. Over a median follow-up of 13 years, 290 HF and 828 CVD events occurred. Elevated BMI at each age point (age 20, age 40, and MESA baseline) was independently associated with HF, and to lesser extent with CVD ( Figure ). After adjustment for demographics, CVD risk factors, and baseline BMI, higher self-reported BMIs at ages 20 and 40 years were independently associated with increased risk of incident HF with hazard ratios (HR) 1.18 (95% CI 1.05-1.32) and 1.30 (1.15-1.46), respectively, per 1 SD higher BMI. Participants with self-reported obesity (BMI≥30) at age 20 [HR 3.20 (1.93-5.32)] and age 40 [HR 1.92 (1.31-2.83)] had greater HF risk, even after accounting for current BMI. For incident CVD, only higher self-reported BMI at age 20 (per 1 SD) was associated after accounting for current BMI [HR 1.09 (1.01-1.17)]. Conclusions: Assessment of self-reported lifetime weights is a simple tool utilized in any clinical encounter. Although subject to recall bias, self-reported weights provide prognostic information about future HF risk, incremental to current BMI, in a multi-ethnic cohort of middle-aged to older adults.

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Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk

International Journal of Molecular Sciences ◽

10.3390/ijms22031383 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1383

Author(s):

Timothy E. O’Toole ◽

Xiaohong Li ◽

Daniel W. Riggs ◽

David J. Hoetker ◽

Shahid P. Baba ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Density Lipoprotein ◽

High Sensitivity ◽

Cvd Risk ◽

Reactive Protein ◽

Heart Study ◽

Urinary Levels

Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine) which supports physiological homeostasis by buffering intracellular pH, chelating metals, and conjugating with and neutralizing toxic aldehydes such as acrolein. However, it is not clear if carnosine can support cardiovascular function or modify cardiovascular disease (CVD) risk. To examine this, we measured urinary levels of nonconjugated carnosine and its acrolein conjugates (carnosine-propanal and carnosine-propanol) in participants of the Louisville Healthy Heart Study and examined associations with indices of CVD risk. We found that nonconjugated carnosine was significantly associated with hypertension (p = 0.011), heart failure (p = 0.015), those categorized with high CVD risk (p < 0.001), body mass index (BMI; p = 0.007), high sensitivity C-reactive protein (hsCRP; p = 0.026), high-density lipoprotein (HDL; p = 0.007) and certain medication uses. Levels of carnosine-propanal and carnosine-propanol demonstrated significant associations with BMI, blood glucose, HDL and diagnosis of diabetes. Carnosine-propanal was also associated with heart failure (p = 0.045) and hyperlipidemia (p = 0.002), but no associations with myocardial infarction or stroke were identified. We found that the positive associations of carnosine conjugates with diabetes and HDL remain statistically significant (p < 0.05) in an adjusted, linear regression model. These findings suggest that urinary levels of nonconjugated carnosine, carnosine-propanal and carnosine-propanol may be informative biomarkers for the assessment of CVD risk—and particularly reflective of skeletal muscle injury and carnosine depletion in diabetes.

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Abstract P346: Joint Associations of Obstructive Sleep Apnea and Excessive Daytime Sleepiness With Incident Cardiovascular Disease

Circulation ◽

10.1161/circ.137.suppl_1.p346 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Rachel P Ogilvie ◽

Kamakshi Lakshminarayan ◽

Sanjay R Patel ◽

Pamela L Lutsey

Keyword(s):

Cardiovascular Disease ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Hazard Ratio ◽

Cvd Risk ◽

Obstructive Sleep ◽

Increased Risk ◽

Incident Cases

Background: Although excessive daytime sleepiness (EDS) is a common symptom of obstructive sleep apnea (OSA), and both EDS and OSA have separately been associated with increased risk of cardiovascular disease (CVD), their joint association with CVD risk is unknown. Examining the association of EDS and OSA with CVD risk may help refine the OSA phenotype. Methods: Among 3,874 Sleep Heart Health Study participants without prevalent CVD, moderate to severe OSA was defined by an apnea hypopnea index (AHI) ≥ 15 events per hour on in-home polysomnography. EDS was defined as an Epworth Sleepiness Scale score ≥ 11. Incident CVD events included adjudicated myocardial infarction, coronary revascularization and stroke. Cox proportional hazards models adjusted for age, sex, alcohol, smoking, and body mass index. Results: Mean age was 63.0 years with 55.4% female, mean AHI 9.3 events/hour, and 23.4% with EDS. Over a median of 10.4 years of follow-up, we identified 653 incident cases of CVD. In adjusted analyses, EDS (Hazard ratio: 1.22, 95% CI 1.01-1.47) but not moderate-severe OSA (HR: 0.98, 0.81-1.20) was associated with incident CVD. In stratified analyses, the CVD incidence rate varied from 15.6/1000 person-years in those with no OSA or EDS to 26.0/1000 person-years in those with OSA and EDS (figure). In multivariable analyses, the hazard ratio for moderate-severe OSA and EDS compared to no OSA and no EDS was 1.26 (0.91-1.73). Formal tests of statistical significance of the OSA and EDS interaction were not significant on either the additive or multiplicative scales. Conclusions: Having both EDS and moderate-severe OSA was not associated with an increased risk of CVD in our data.

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