Sverrir I. Gunnarsson

Obstructive Sleep Apnea Is Associated With Future Subclinical Carotid Artery Disease Thirteen-Year Follow-Up From the Wisconsin Sleep Cohort

Objective— To determine the longitudinal associations between obstructive sleep apnea, carotid artery intima-media thickness (IMT), and plaque. Approach and Results— This is a population-based, prospective cohort study conducted from July, 1989, to November, 2012, on 790 randomly selected Wisconsin residents who completed a mean of 3.5 (range, 1–6) polysomnograms during the study period. Obstructive sleep apnea was characterized by the apnea–hypopnea index (AHI, events/h). Common carotid artery IMT and plaque were assessed by B-mode ultrasound. The mean (SD) time from the first polysomnograms to carotid ultrasound was 13.5 (3.6) years. Multivariable regression models were created to estimate the independent associations of baseline and cumulative obstructive sleep apnea exposure with subsequent carotid IMT and plaque. At baseline, the mean age of participants was 47.6 (7.7) years (55% men, 97% white). AHI was 4.4 (9.0) events/h (range, 0–97); 7% had AHI >15 events/h. Carotid IMT was 0.755 (0.161) mm; 63% had plaque. Adjusting for age, sex, body mass index, systolic blood pressure, smoking, and use of lipid-lowering, antihypertensive, and antidiabetic medications, baseline AHI independently predicted future carotid IMT (&bgr;=0.027 mm/unit log10[AHI+1]; P=0.049), plaque presence (odds ratio, 1.55 [95% confidence intervals, 1.02–2.35]; P=0.041) and plaque score (odds ratio, 1.30 [1.05–1.61]; P=0.018). In cumulative risk factor–adjusted models, AHI independently predicted future carotid plaque presence (P=0.012) and score (P=0.039), but not IMT (P=0.608). Conclusions— Prevalent obstructive sleep apnea is independently associated with increased carotid IMT and plaque more than a decade later, indicating increased future cardiovascular disease risk.Objective— To determine the longitudinal associations between obstructive sleep apnea, carotid artery intima-media thickness (IMT), and plaque. Approach and Results— This is a population-based, prospective cohort study conducted from July, 1989, to November, 2012, on 790 randomly selected Wisconsin residents who completed a mean of 3.5 (range, 1–6) polysomnograms during the study period. Obstructive sleep apnea was characterized by the apnea–hypopnea index (AHI, events/h). Common carotid artery IMT and plaque were assessed by B-mode ultrasound. The mean (SD) time from the first polysomnograms to carotid ultrasound was 13.5 (3.6) years. Multivariable regression models were created to estimate the independent associations of baseline and cumulative obstructive sleep apnea exposure with subsequent carotid IMT and plaque. At baseline, the mean age of participants was 47.6 (7.7) years (55% men, 97% white). AHI was 4.4 (9.0) events/h (range, 0–97); 7% had AHI >15 events/h. Carotid IMT was 0.755 (0.161) mm; 63% had plaque. Adjusting for age, sex, body mass index, systolic blood pressure, smoking, and use of lipid-lowering, antihypertensive, and antidiabetic medications, baseline AHI independently predicted future carotid IMT (β=0.027 mm/unit log10[AHI+1]; P =0.049), plaque presence (odds ratio, 1.55 [95% confidence intervals, 1.02–2.35]; P =0.041) and plaque score (odds ratio, 1.30 [1.05–1.61]; P =0.018). In cumulative risk factor–adjusted models, AHI independently predicted future carotid plaque presence ( P =0.012) and score ( P =0.039), but not IMT ( P =0.608). Conclusions— Prevalent obstructive sleep apnea is independently associated with increased carotid IMT and plaque more than a decade later, indicating increased future cardiovascular disease risk. # Significance {#article-title-30}

Minimal nocturnal oxygen saturation predicts future subclinical carotid atherosclerosis: the Wisconsin sleep cohort.

Previous data on the associations between nocturnal oxygen saturation parameters and carotid atherosclerosis are conflicting. We examined the prospective associations of nocturnal oxygen saturation (SaO2) and cardiovascular disease (CVD) risk factors with carotid intima‐media thickness (IMT) and plaques. We used data on 689 Wisconsin sleep cohort participants who had baseline overnight polysomnography followed by carotid ultrasonography a mean (SD) of 7.8 (2.5) years later. Far wall common carotid IMT was measured using B‐mode ultrasound. Bilateral common, bifurcation and internal carotid artery segments were evaluated for plaque score. Participants (8) were aged 56 years (55% male); 32% had hypertension and mean body mass index (BMI) was 31 (7) kg m2. Mean and minimum nocturnal SaO2 were 95% (2) and 86% (7), respectively. Mean percentage sleep time with SaO2 < 90% was 2% (8). Both mean (odds ratio [OR]: 0.60 lower plaque count per 5% higher mean SaO2, 95% confidence interval [CI]: 0.38–0.96, P = 0.033) and minimum SaO2 (OR: 0.88 lower plaque count per 5% higher minimum SaO2, 95% CI: 0.80–0.97, P = 0.013) predicted carotid plaque score after adjusting for age, sex and BMI. Minimum SaO2 predicted future plaque score after adding adjustment for traditional CVD risk factors (OR: 0.90 lower plaque count per 5% higher minimum SaO2, 95% CI: 0.81–0.99, P = 0.038). Mean SaO2 was not associated with carotid IMT after CVD risk factor adjustment. We conclude that minimum nocturnal SaO2 is an independent predictor of future carotid plaque burden. Other nocturnal SaO2 parameters are not associated with future carotid IMT or plaques after adjusting for traditional CVD risk factors.

A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta

Abstract Aims Coarctation of the aorta (CoA) accounts for 4–8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment. It is increasingly recognized as a highly heritable condition. The aim of the study was to search for sequence variants that affect the risk of CoA. Methods and results We performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing. We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10−22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein. Approximately 20% of individuals with CoA in Iceland carry this mutation. We show that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic valve. We have previously reported broad effects of p.Arg721Trp on cardiac electrical function and strong association with sick sinus syndrome and atrial fibrillation. Conclusion Through a population approach, we found that a rare missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on the risk of CoA and explains a substantial fraction of the Icelanders with CoA. This is the first mutation associated with non-familial or sporadic form of CoA at a population level. The p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity and emphasizes the importance of sarcomere integrity for cardiac development and function.

A rare missense mutation in MYH6 confers high risk of coarctation of the aorta

Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and carries substantial morbidity despite treatment1. We performed a genome-wide association study (GWAS) of CoA among 120 Icelandic cases and 355,166 controls and found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio (OR) = 44.2, P = 5.0x10-22), encoding an essential sarcomere protein. Approximately 20% of CoA cases in Iceland carry p.Arg721Trp. This is the first mutation associated with non-familial or sporadic CoA at a population level. P.Arg721Trp also associates with risk of bicuspid aortic valve (BAV) and other CHDs and has been reported to have a broad effect on cardiac electrical function and to associate strongly with sick sinus syndrome (SSS) and atrial fibrillation (AF)2. These findings suggest that p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity, and emphasize the major importance of sarcomere integrity for cardiac development and function.

Outcomes of Physician‐Staffed Versus Non‐Physician‐Staffed Helicopter Transport for ST‐Elevation Myocardial Infarction

Background The effect of physician‐staffed helicopter emergency medical service (HEMS) on ST‐elevation myocardial infarction (STEMI) patient transfer is unknown. The purpose of this study was to evaluate the characteristics and outcomes of physician‐staffed HEMS (Physician‐HEMS) versus non‐physician‐staffed (Standard‐HEMS) in patients with STEMI. Methods and Results We studied 398 STEMI patients transferred by either Physician‐HEMS (n=327) or Standard‐HEMS (n=71) for primary or rescue percutaneous coronary intervention at 2 hospitals between 2006 and 2014. Data were collected from electronic medical records and each institutions contribution to the National Cardiovascular Data Registry. Baseline characteristics were similar between groups. Median electrocardiogram‐to‐balloon time was longer for the Standard‐HEMS group than for the Physician‐HEMS group (118 vs 107 minutes; P=0.002). The Standard‐HEMS group was more likely than the Physician‐HEMS group to receive nitroglycerin (37% vs 15%; P<0.001) and opioid analgesics (42.3% vs 21.7%; P<0.001) during transport. In‐hospital adverse outcomes, including cardiac arrest, cardiogenic shock, and serious arrhythmias, were more common in the Standard‐HEMS group (25.4% vs 11.3%; P=0.002). After adjusting for age, sex, Killip class, and transport time, patients transferred by Standard‐HEMS had increased risk of any serious in‐hospital adverse event (odds ratio=2.91; 95% CI=1.39–6.06; P=0.004). In‐hospital mortality was not statistically different between the 2 groups (9.9% in the Standard‐HEMS group vs 4.9% in the Physician‐HEMS group; P=0.104). Conclusions Patients with STEMI transported by Standard‐HEMS had longer transport times, higher rates of nitroglycerin and opioid administration, and higher rates of adjusted in‐hospital events. Efforts to better understand optimal transport strategies in STEMI patients are needed.

ASSOCIATION OF NOCTURNAL OXYGEN SATURATION WITH FUTURE SUBCLINICAL CAROTID ARTERY DISEASE: THE WISCONSIN SLEEP COHORT

Sleep-disordered breathing (SDB) is associated with increased cardiovascular disease (CVD) risk. However, the contributions of traditional CVD risk factors (e.g., hypertension) relative to SDB are unknown. We evaluated longitudinal associations of nocturnal 02 saturation (SaO2) and CVD risk factors

Obstructive Sleep Apnea Is Associated With Future Subclinical Carotid Artery DiseaseSignificance

Objective— To determine the longitudinal associations between obstructive sleep apnea, carotid artery intima-media thickness (IMT), and plaque. Approach and Results— This is a population-based, prospective cohort study conducted from July, 1989, to November, 2012, on 790 randomly selected Wisconsin residents who completed a mean of 3.5 (range, 1–6) polysomnograms during the study period. Obstructive sleep apnea was characterized by the apnea–hypopnea index (AHI, events/h). Common carotid artery IMT and plaque were assessed by B-mode ultrasound. The mean (SD) time from the first polysomnograms to carotid ultrasound was 13.5 (3.6) years. Multivariable regression models were created to estimate the independent associations of baseline and cumulative obstructive sleep apnea exposure with subsequent carotid IMT and plaque. At baseline, the mean age of participants was 47.6 (7.7) years (55% men, 97% white). AHI was 4.4 (9.0) events/h (range, 0–97); 7% had AHI >15 events/h. Carotid IMT was 0.755 (0.161) mm; 63% had plaque. Adjusting for age, sex, body mass index, systolic blood pressure, smoking, and use of lipid-lowering, antihypertensive, and antidiabetic medications, baseline AHI independently predicted future carotid IMT (&bgr;=0.027 mm/unit log10[AHI+1]; P=0.049), plaque presence (odds ratio, 1.55 [95% confidence intervals, 1.02–2.35]; P=0.041) and plaque score (odds ratio, 1.30 [1.05–1.61]; P=0.018). In cumulative risk factor–adjusted models, AHI independently predicted future carotid plaque presence (P=0.012) and score (P=0.039), but not IMT (P=0.608). Conclusions— Prevalent obstructive sleep apnea is independently associated with increased carotid IMT and plaque more than a decade later, indicating increased future cardiovascular disease risk.Objective— To determine the longitudinal associations between obstructive sleep apnea, carotid artery intima-media thickness (IMT), and plaque. Approach and Results— This is a population-based, prospective cohort study conducted from July, 1989, to November, 2012, on 790 randomly selected Wisconsin residents who completed a mean of 3.5 (range, 1–6) polysomnograms during the study period. Obstructive sleep apnea was characterized by the apnea–hypopnea index (AHI, events/h). Common carotid artery IMT and plaque were assessed by B-mode ultrasound. The mean (SD) time from the first polysomnograms to carotid ultrasound was 13.5 (3.6) years. Multivariable regression models were created to estimate the independent associations of baseline and cumulative obstructive sleep apnea exposure with subsequent carotid IMT and plaque. At baseline, the mean age of participants was 47.6 (7.7) years (55% men, 97% white). AHI was 4.4 (9.0) events/h (range, 0–97); 7% had AHI >15 events/h. Carotid IMT was 0.755 (0.161) mm; 63% had plaque. Adjusting for age, sex, body mass index, systolic blood pressure, smoking, and use of lipid-lowering, antihypertensive, and antidiabetic medications, baseline AHI independently predicted future carotid IMT (β=0.027 mm/unit log10[AHI+1]; P =0.049), plaque presence (odds ratio, 1.55 [95% confidence intervals, 1.02–2.35]; P =0.041) and plaque score (odds ratio, 1.30 [1.05–1.61]; P =0.018). In cumulative risk factor–adjusted models, AHI independently predicted future carotid plaque presence ( P =0.012) and score ( P =0.039), but not IMT ( P =0.608). Conclusions— Prevalent obstructive sleep apnea is independently associated with increased carotid IMT and plaque more than a decade later, indicating increased future cardiovascular disease risk. # Significance {#article-title-30}

Obstructive Sleep Apnea Is Associated With Future Subclinical Carotid Artery Disease

Objective— To determine the longitudinal associations between obstructive sleep apnea, carotid artery intima-media thickness (IMT), and plaque. Approach and Results— This is a population-based, prospective cohort study conducted from July, 1989, to November, 2012, on 790 randomly selected Wisconsin residents who completed a mean of 3.5 (range, 1–6) polysomnograms during the study period. Obstructive sleep apnea was characterized by the apnea–hypopnea index (AHI, events/h). Common carotid artery IMT and plaque were assessed by B-mode ultrasound. The mean (SD) time from the first polysomnograms to carotid ultrasound was 13.5 (3.6) years. Multivariable regression models were created to estimate the independent associations of baseline and cumulative obstructive sleep apnea exposure with subsequent carotid IMT and plaque. At baseline, the mean age of participants was 47.6 (7.7) years (55% men, 97% white). AHI was 4.4 (9.0) events/h (range, 0–97); 7% had AHI >15 events/h. Carotid IMT was 0.755 (0.161) mm; 63% had plaque. Adjusting for age, sex, body mass index, systolic blood pressure, smoking, and use of lipid-lowering, antihypertensive, and antidiabetic medications, baseline AHI independently predicted future carotid IMT (&bgr;=0.027 mm/unit log10[AHI+1]; P=0.049), plaque presence (odds ratio, 1.55 [95% confidence intervals, 1.02–2.35]; P=0.041) and plaque score (odds ratio, 1.30 [1.05–1.61]; P=0.018). In cumulative risk factor–adjusted models, AHI independently predicted future carotid plaque presence (P=0.012) and score (P=0.039), but not IMT (P=0.608). Conclusions— Prevalent obstructive sleep apnea is independently associated with increased carotid IMT and plaque more than a decade later, indicating increased future cardiovascular disease risk.Objective— To determine the longitudinal associations between obstructive sleep apnea, carotid artery intima-media thickness (IMT), and plaque. Approach and Results— This is a population-based, prospective cohort study conducted from July, 1989, to November, 2012, on 790 randomly selected Wisconsin residents who completed a mean of 3.5 (range, 1–6) polysomnograms during the study period. Obstructive sleep apnea was characterized by the apnea–hypopnea index (AHI, events/h). Common carotid artery IMT and plaque were assessed by B-mode ultrasound. The mean (SD) time from the first polysomnograms to carotid ultrasound was 13.5 (3.6) years. Multivariable regression models were created to estimate the independent associations of baseline and cumulative obstructive sleep apnea exposure with subsequent carotid IMT and plaque. At baseline, the mean age of participants was 47.6 (7.7) years (55% men, 97% white). AHI was 4.4 (9.0) events/h (range, 0–97); 7% had AHI >15 events/h. Carotid IMT was 0.755 (0.161) mm; 63% had plaque. Adjusting for age, sex, body mass index, systolic blood pressure, smoking, and use of lipid-lowering, antihypertensive, and antidiabetic medications, baseline AHI independently predicted future carotid IMT (β=0.027 mm/unit log10[AHI+1]; P =0.049), plaque presence (odds ratio, 1.55 [95% confidence intervals, 1.02–2.35]; P =0.041) and plaque score (odds ratio, 1.30 [1.05–1.61]; P =0.018). In cumulative risk factor–adjusted models, AHI independently predicted future carotid plaque presence ( P =0.012) and score ( P =0.039), but not IMT ( P =0.608). Conclusions— Prevalent obstructive sleep apnea is independently associated with increased carotid IMT and plaque more than a decade later, indicating increased future cardiovascular disease risk. # Significance {#article-title-30}