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Objective To examine whether experimentally induced weight gain raises ambulatory blood pressure (BP) in healthy subjects and identify any relationship between changes in BP and changes in regional fat distribution. Patients and Methods Twenty-six normal weight subjects were randomized to 8 weeks of weight gain through overfeeding (n=16; age, 30.4±6.6 years) or to weight maintenance (controls; n=10; age, 27.1±7.7 years) between July 2004 and August 2010. Measures of body composition via dual energy X-ray absorptiometry and computed tomography, circulating biomarkers, and 24-hour ambulatory BP were obtained at baseline and after the 8-week experimental phase. Results Overfeeding resulted in 3.7 kg (95% CI, 2.9-4.5) increase in body weight in weight gainers, with increments in total (46.2 cm2; 95% CI, 27.6-64.9), visceral (13.8 cm2; 95% CI, 5.8-21.9), and subcutaneous fat (32.4 cm2; 95% CI, 13.5-51.3). No changes occurred in the maintenance group. Increases in 24-hour systolic BP (4 mm Hg; 95% CI, 1.6-6.3), mean BP (1.7 mm Hg; 95% CI, 0.3-3.3), and pulse pressure (2.8 mm Hg; 95% CI, 1.1-4.4) were evident after weight gain in the experimental group, whereas BP remained unchanged in controls. Changes in mean BP correlated only with changes in visceral fat (ρ=0.45; P=.02), but not with changes in other body composition measures. Conclusion Modest weight gain causes elevation in 24-hour BP in healthy subjects. The association between increased BP and abdominal visceral fat accumulation suggests that visceral deposition of adipose tissue may contribute specifically to the enhanced risk of hypertension associated with weight gain.

Sleep apnea (SA) is associated with intermittent hypoxemia that may lead to ischemic preconditioning in the myocardium. This potential cardioprotective effect of SA may play a role in the development of non-ST-elevation myocardial infarction (NSTEMI) versus ST-elevation myocardial infarction (STEMI) during acute ischemia. However, there is limited evidence about the relative prevalence of NSTEMI versus STEMI in SA patients. We therefore prospectively investigated the prevalence of these two types of MI in patients with SA.We prospectively studied 782 consecutive patients admitted with the diagnosis of acute MI (both NSTEMI and STEMI). All subjects underwent sleep evaluations using a portable diagnostic device after at least 48h post-admission, provided they were in stable condition. Six hundred and seven out of 782 patients had technically adequate sleep studies, and therefore were included in the final analysis.SA was present in 65.7% (n=399) and NSTEMI in 30% (n=182) of patients. Increasing severity of SA was associated with increasing likelihood of NSTEMI, and with decreasing likelihood of STEMI (p0.001). Relative frequency of NSTEMI in the moderate to severe SA group (AHI≥15events/h) was 40.6% versus 29.9% for STEMI (p=0.01).The prevalence of NSTEMI increases with increasing severity of SA. This finding may suggest a cardioprotective role of SA, which may attenuate the development of STEMI, perhaps through ischemic preconditioning.

Background: Abdominal fat elevates while lower-body (LB) fat diminishes cardiovascular risk. However, molecular mechanisms differentiating the two fat depots are not completely understood. MicroRNA (miRNA) are important regulators of gene expression with widespread effects on several proteins. Objective: To explore miRNA differences between the two fat depots using unbiased next-generation sequencing (NGS) approach. Methods: Total RNA isolated from paired subcutaneous (sc) fat tissue obtained from abdomen (ABD) and LB (femoral) region of 12 healthy subjects (7 male; age: 27 ± 5 years; BMI: 23.5 ± 3.2 kg/m 2 ) was used to quantify miRNA expression. Body fat distribution was determined using dual-energy X-ray absorptiometry and abdominal computed tomography scans. RNA was prepped using the NEBNext small RNA library prep kit and sequenced using Illumina HiSeq 2000. Raw sequence data were processed using CAP-miRSeq pipeline. miRNA expression between the two depots was evaluated using EdgeR. Relationship between miRNA and regional fat depots were examined using Spearman’s correlation. Adjusted or unadjusted P value Results: Using NGS, 383 ± 55 known miRNA with ≥5 raw reads were detected in the study samples. Principal component analysis including all miRNAs showed no any clear separation between ABD or LB fat tissue. However, 37 miRNAs were found to have altered expression in the two depots. miR-196a-5p (log2FC=1.138, p Conclusions: Several miRNAs are differentially expressed between ABD and LB fat tissue which may partly contribute to depot specific alterations in adipose tissue function and consequent cardiometabolic risk. Furthermore, the associations between miRNA and regional fat depots suggest a functional role of these miRNA in fat distribution.

Background Excessive daytime sleepiness ( EDS ), a common symptom among patients with sleep‐disordered breathing, is closely associated with the development of cardiovascular diseases, but its long‐term prognostic value is not completely understood. The aim of this study was to investigate whether EDS would be an independent prognostic factor after myocardial infarction. Methods and Results We prospectively recruited 112 post–myocardial infarction patients. The Epworth Sleepiness Scale was completed before polysomnography, and EDS was defined as a score ≥11. After exclusion of 8 patients who accepted treatment with continuous positive airway pressure, 104 patients were followed up for 48 months. The primary composite end point was major adverse cardiac events. Patients with EDS had higher rates of major adverse cardiac events (48.4% versus 27.4%, χ 2 =5.27, P =0.022) and reinfarction (29.0% versus 5.5%, χ 2 =13.51, P =0.0002) compared with those without EDS . In the Cox proportional hazards model, patients with EDS had 2.15 times (95% confidence interval, 1.08–4.18; P =0.030) higher crude risk of major adverse cardiac events, with prognostic significance persisting after adjusting for age, diabetes mellitus, depression, left ventricular ejection fraction, apnea–hypopnea index, and nocturnal nadir oxygen saturation (hazard ratio: 2.13, 95% confidence interval, 1.04–4.26, P =0.039). Furthermore, among participants with moderate to severe sleep‐disordered breathing, the presence of EDS was associated with higher risk of major adverse cardiac events than those without EDS , after adjusting for age and nadir oxygen saturation (hazard ratio: 3.17, 95% confidence interval, 1.22–7.76, P =0.019). Conclusions EDS may be an independent prognostic factor of adverse outcome in post–myocardial infarction patients with moderate to severe sleep‐disordered breathing. Evaluation of EDS may shed new light on risk stratification and identify treatment responders for this patient population.

Background/Objective Adiponectin exerts beneficial effects by reducing inflammation, and improving lipid metabolism and insulin-sensitivity. Although adiponectin is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. Methods/Results Forty four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8-weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8 ± 1.2 kg resulted in increased adiponectin (p=0.03) while weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (p=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, while a leptin-antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in adipose tissue from normal-weight participants, but did not do so in adipose tissue from obese participants; and second, that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin. Conclusions Modest weight gain in healthy individuals is associated with increases in adiponectin, which correlate positively with changes in leptin. In-vitro, leptin induces adiponectin expression which is attenuated by increased caveolin-1 expression. Additionally, adipose tissue from obese subjects shows increased caveolin-1 expression, and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.

The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age of 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea or congenital long QT syndrome.

Although laboratory stressor tests have been applied as a preliminary protocol in some cardiovascular studies, there is a lack of data comparing the pressor and chronotropic responses among the main stressor tests. Therefore, the aim of this study was to evaluate the variability in hemodynamic responsiveness to the main stressor tests, establish a hyperresponsiveness cutoff criterion and analyze the influence of gender and family history of cardiovascular diseases (CVDs) in healthy subjects. We examined hemodynamic responses to physical (cold pressor and handgrip tests) and mental (Stroop color-word test) stressors in 98 subjects (48 males and 50 females) without CVDs. All stressor tests resulted in increased blood pressure (BP) levels, which were lower and less dispersed in the handgrip test compared to the cold pressor test. Adopting the 75(th) percentile as the cutoff in our data, we classified subjects exhibiting absolute pressor changes equal to or higher than 14, 24 and 36 mmHg in systolic and 9, 13 and 24 mmHg in diastolic BP during the handgrip, Stroop and cold pressor test, respectively, as hyperresponsives. Males exhibited greater (p

Asian Indians have markedly increased mortality due to coronary artery disease (CAD). Impaired endothelial function has been linked to an increased risk of acute cardiovascular events. We tested the hypothesis that endothelial function was attenuated in Asian Indians and Caucasians.We studied 14 Asian Indians [mean age: 30 ± 6 years; mean body mass index (BMI): 25 ± 3 kg/m(2)] and 11 Caucasians (mean age: 30 ± 5 years; mean BMI: 26 ± 2 kg/m(2)). All 25 subjects were healthy men and nonsmokers without any history of CAD or diabetes and were not taking medications. Endothelial function was evaluated by ultrasound measures of flow-mediated dilatation (FMD) and endothelium-independent nonflow mediated vasodilatation (NFMD) of the brachial artery, in the morning immediately after awakening (6 a.m.) in a fasting state.Mean age, BMI, apnea-hypopnea index, heart rate, and blood pressure were similar in both groups (P = 0.05). When correcting for body surface area, brachial artery diameter was not different between the two groups (2.1% ± 0.3% vs. 2.2% ± 0.4%; P = 0.29). FMD and NFMD were similar in Asian Indians and Caucasians (5.9% ± 4.1% vs. 5.7% ± 2.6%, P = 0.70; 16.4% ± 8% vs. 14.8% ± 4.1%, P = 0.58, respectively).Endothelial function in Asian Indian men is not attenuated in comparison to Caucasian men.

Background: Normal-weight adults gain lower-body fat via adipocyte hyperplasia and upper-body subcutaneous (UBSQ) fat via adipocyte hypertrophy. Objectives: We investigated whether regional fat loss mirrors fat gain and whether the loss of lower-body fat is attributed to decreased adipocyte number or size. Design: We assessed UBSQ, lower-body, and visceral fat gains and losses in response to overfeeding and underfeeding in 23 normalweight adults (15 men) by using dual-energy X-ray absorptiometry and abdominal computed tomography scans. Participants gained w5% of weight in 8 wk and lost w80% of gained fat in 8 wk. We measured abdominal subcutaneous and femoral adipocyte sizes and numbers after weight gain and loss. Results: Volunteers gained 3.1 6 2.1 (mean 6 SD) kg body fat with overfeeding and lost 2.4 6 1.7 kg body fat with underfeeding. Although UBSQ and visceral fat gains were completely reversed after 8 wk of underfeeding, lower-body fat had not yet returned to baseline values. Abdominal and femoral adipocyte sizes, but not numbers, decreased with weight loss. Decreases in abdominal adipocyte size and UBSQ fat mass were correlated (r = 0.76, P = 0.001), as were decreases in femoral adipocyte size and lower-body fat (r = 0.49, P = 0.05). Conclusions: UBSQ and visceral fat increase and decrease proportionately with a short-term weight gain and loss, whereas a gain of lower-body fat does not relate to the loss of lower-body fat. The loss of lower-body fat is attributed to a reduced fat cell size, but not number, which may result in long-term increases in fat cell numbers. Am J Clin Nutr 2012;96:229–33.

Background The Berlin Questionnaire (BQ) has been used to identify patients at high risk for sleep-disordered breathing (SDB) in a variety of populations. However, there are no data regarding the validity of the BQ in detecting the presence of SDB in patients after myocardial infarction (MI). The aim of this study was to determine the performance of the BQ in patients after MI. Methods We conducted a cross-sectional study of 99 patients who had an MI 1 to 3 months previously. The BQ was administered, scored using the published methods, and followed by completed overnight polysomnography as the "gold standard." SDB was defined as an apnea-hypopnea index of ≥ 5 events/h. The sensitivity, specificity, and positive and negative predictive values of the BQ were calculated. Results Of the 99 patients, the BQ identified 64 (65%) as being at high-risk for having SDB. Overnight polysomnography showed that 73 (73%) had SDB. The BQ sensitivity and specificity was 0.68 and 0.34, respectively, with a positive predictive value of 0.68 and a negative predictive value of 0.50. Positive and negative likelihood ratios were 1.27 and 0.68, respectively, and the BQ overall diagnostic accuracy was 63%. Using different apnea-hypopnea index cutoff values did not meaningfully alter these results. Conclusion The BQ performed with modest sensitivity, but the specificity was poor, suggesting that the BQ is not ideal in identifying SDB in patients with a recent MI.

Background Obstructive sleep apnea (OSA) has been recognized as a risk factor for cardiovascular disease and mortality. The aim of this study was to determine the feasibility and efficacy of implementing a screening program for OSA in early outpatient cardiac rehabilitation (CR) and to estimate the risk for OSA in this population. Methods From 535 consecutive patients enrolled in early outpatient CR we screened 383 (72%) patients and classified them as low- vs. high-risk for OSA using the Berlin questionnaire. Those considered at high-risk for OSA were referred for further evaluation. We assessed the yield and feasibility of the screening program, patient compliance with referral, and the percentage of patients diagnosed with OSA after polysomnography. Results Mean age was 63 ± 12 years, 70% were men, 20% had diabetes, 65% had hypertension, and 58% had experienced a recent myocardial infarction. Two hundred and one patients (52%) had a high risk for OSA based on the questionnaire. Of the 169 who completed the CR program, only 111 (78%) were referred for further evaluation ( Fig. 1 ). Of the 74 patients who completed their OSA work-up, 39 were found to have OSA with an apnea–hypopnea index of ⩾5 events/h. Conclusions Implementation of a simple screening program for OSA in early outpatient CR is feasible with minimal incremental resources. A significant percentage of patients at high-risk decline further evaluation, suggesting that their perceived risk for OSA and its consequences may be low.

Objective To determine the role of hyperleptinemia on caveolin-1 expression and leptin signaling.

Objectives The aim of this study was to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans. Background Endothelial dysfunction has been identified as an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown. Methods A randomized controlled study was conducted to assess the effects of fat gain on endothelial function. Forty-three normal-weight healthy volunteers were recruited (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n = 35) or to maintain weight (n = 8). Endothelial function (brachial artery flow-mediated dilation [FMD]) was measured at baseline, after fat gain (8 weeks), and after weight loss (16 weeks) for fat gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition was measured by dual-energy X-ray absorptiometry and abdominal computed tomographic scans. Results After an average weight gain of 4.1 kg, fat gainers significantly increased their total, visceral, and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight maintainers. FMD decreased in fat gainers (9.1 ± 3% vs. 7.8 ± 3.2%, p = 0.003) but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho = −0.42, p = 0.004), but not with subcutaneous fat gain (rho = −0.22, p = 0.15). Conclusions In normal-weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. (Fat Gain and Cardiovascular Disease Mechanisms; NCT00589498 )

A prothrombotic state in obesity may be partially responsible for the higher incidence of atherosclerotic complications. However the factors responsible for this prothrombotic state, linked with high levels of plasminogen activator inhibitor-1 (PAI-1), are not fully known. Leptin is elevated in obesity and studies have shown a positive correlation between leptin and PAI-1 levels in human subjects, along with a negative correlation with tissue type plasminogen activator (tPA). We tested the hypothesis that leptin induces PAI-1 and inhibits tPA expression using human coronary artery endothelial cells (HCAEC) in culture as these cells play an important role in atherosclerosis. We demonstrate that leptin induces the transcription and translation of PAI-1 in HCAEC. The leptin dependent upregulation of PAI-1 mRNA and protein was comparable to insulin-induced PAI-1 expression. We show leptin concentration (0-150 ng/ml) dependent increases in PAI-1 mRNA and protein after six and twelve hours of leptin administration respectively. Increased intracellular PAI-1 expression correlates with increased PAI-1 activity in conditioned media and inhibition of specific ERK1/2 pathway by treatment with PD98059 (20 to 40 μM) inhibits leptin dependent PAI-1 expression. However no changes in tPA expression were seen with time or increasing concentrations of leptin. Also leptin treatment did not alter total tPA concentration or tPA activity in conditioned media. In conclusion, our study shows that leptin up-regulates the expression of PAI-1 in vascular endothelial cells via activation of ERK1/2 but does not regulate tPA expression. These studies demonstrate a novel mechanism for the prothrombotic role of leptin in development of atherosclerosis.

Sex differences in morbidity and mortality associated with cardiovascular disease have been recognized by the medical community for decades. Investigation into the underlying biological basis of these differences was largely neglected by the scientific community until a report released by the Institute of Medicine in the United States in 2001 "Exploring the Biological Contributions to Human Health: Does Sex Matter?" Recommendations from this report included the need for more accurate use of the terms "sex" and "gender", better tools and resources to study the biological basis of sex differences, integration of findings from different levels of biological organization and continued synergy between basic and clinical researchers. Ten years after the Institute's report, this review evaluates some of the sex differences in cardiovascular disease, reviews new approaches to study sex differences and emphasizes areas where further research is required. In the era of personalized medicine, the study of the biological basis of sex differences promises to optimize preventive, diagnostic and therapeutic strategies for cardiovascular disease in men and women, but will require diligence by the scientific and medical communities to remember that sex does matter.

Objectives This study sought to evaluate the day–night variation of acute myocardial infarction (MI) in patients with obstructive sleep apnea (OSA). Background Obstructive sleep apnea has a high prevalence and is characterized by acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of MI during the night. Methods We prospectively studied 92 patients with MI for which the time of onset of chest pain was clearly identified. The presence of OSA was determined by overnight polysomnography. Results For patients with and without OSA, we compared the frequency of MI during different intervals of the day based on the onset time of chest pain. The groups had similar prevalence of comorbidities. Myocardial infarction occurred between 12 am and 6 am in 32% of OSA patients and 7% of non-OSA patients (p = 0.01). The odds of having OSA in those patients whose MI occurred between 12 am and 6 am was 6-fold higher than in the remaining 18 h of the day (95% confidence interval: 1.3 to 27.3, p = 0.01). Of all patients having an MI between 12 am and 6 am , 91% had OSA. Conclusions The diurnal variation in the onset of MI in OSA patients is strikingly different from the diurnal variation in non-OSA patients. Patients with nocturnal onset of MI have a high likelihood of having OSA. These findings suggest that OSA may be a trigger for MI. Patients having nocturnal onset of MI should be evaluated for OSA, and future research should address the effects of OSA therapy for prevention of nocturnal cardiac events.

ALONG WITH THE EPIDEMIC OF obesity, there is a growing awareness of sleep-disordered breathing as a potential and treatable risk factor for cardiovascular disease. The repetitive nocturnal hypoxemia experienced by patients with obstructive sleep apnea (OSA) is associated with activation of a number of neural, humoral, thrombotic, metabolic, and inflammatory disease mechanisms, all of which have also been implicated in the pathophysiology of cardiac and vascular disease. Activation of these mechanisms is often evident even in patients with OSA who are free of overt cardiovascular disease, suggesting that OSA may conceivably contribute to the initiation and progression of cardiovascular disease (FIGURE 1). SleepapneacanbecategorizedasOSA, in which there is preserved and increased respiratory effort despite partial or complete occlusion of the upper airway; or as central sleep apnea (CSA), in which there is absence of both respiratory efforts and airflow. The apneahypopnea index (ie, the number of apneic and hypopneic events per hour) is used as one index of the presence and severity of sleep apnea. For OSA, an apnea-hypopnea index of 5 to 15 indicates mild apnea; of 15 to 30, moderate apnea; and of greater than 30, severe apnea. Approximately 1 in 5 adults has at least mild OSA (apnea-hypopnea index, 5-15), and 1 in 15 adults has at least moderate OSA (apnea-hypopnea index, 15-30). Other measures of the severity of sleep apnea include the severity of oxygen desaturation and the level of daytime sleepiness. Obstructive sleep apnea is commonly associated with obesity and also is often present in patients with

Body mass index (BMI) is the most widely used measure to diagnose obesity. However, the accuracy of BMI in detecting excess body adiposity in the adult general population is largely unknown. A cross-sectional design of 13 601 subjects (age 20–79.9 years; 49% men) from the Third National Health and Nutrition Examination Survey. Bioelectrical impedance analysis was used to estimate body fat percent (BF%). We assessed the diagnostic performance of BMI using the World Health Organization reference standard for obesity of BF%>25% in men and>35% in women. We tested the correlation between BMI and both BF% and lean mass by sex and age groups adjusted for race. BMI-defined obesity (⩾30 kg m−2) was present in 19.1% of men and 24.7% of women, while BF%-defined obesity was present in 43.9% of men and 52.3% of women. A BMI⩾30 had a high specificity (men=95%, 95% confidence interval (CI), 94–96 and women=99%, 95% CI, 98–100), but a poor sensitivity (men=36%, 95% CI, 35–37 and women=49%, 95% CI, 48–50) to detect BF%-defined obesity. The diagnostic performance of BMI diminished as age increased. In men, BMI had a better correlation with lean mass than with BF%, while in women BMI correlated better with BF% than with lean mass. However, in the intermediate range of BMI (25–29.9 kg m−2), BMI failed to discriminate between BF% and lean mass in both sexes. The accuracy of BMI in diagnosing obesity is limited, particularly for individuals in the intermediate BMI ranges, in men and in the elderly. A BMI cutoff of⩾30 kg m−2 has good specificity but misses more than half of people with excess fat. These results may help to explain the unexpected better survival in overweight/mild obese patients.

Leptin, an adipose tissue-derived hormone, has been linked to cardiovascular outcomes; however, data are limited in the United States population, especially women. To assess the association between leptin concentrations and history of myocardial infarction (MI) and stroke independently of traditional cardiovascular risk factors, we analyzed data from 6,239 subjects (mean age 47 years; 3,336 women) with measurements of serum leptin and full assessment of cardiovascular risk factors from the National Health and Nutrition Examination Survey (NHANES) III. Logistic regression was used to estimate the cross-sectional association of leptin concentrations (highest quartile versus lowest quartile) and history of MI, stroke, and the composite end point of MI or stroke (MI/stroke). Gender-specific models of leptin were adjusted for age, race, dyslipidemia, hypertension, diabetes, smoking, and obesity status. There were 212 men with MI/stroke (5.4%), 154 with MI (4.1%), and 82 with stroke (1.7%). There were 135 women with MI/stroke (2.6%), 74 with MI (1.5%), and 78 with stroke (1.4%). In multivariate analysis, high leptin level was significantly and independently associated with MI/stroke in men (odds ratio [OR] 2.41, 95% confidence interval [CI] 1.20 to 4.93) and women (OR 4.26, 95% CI 1.75 to 10.73); with MI in men (OR 3.16, 95% CI 1.40 to 7.37) and women (OR 3.96, 95% CI 1.29 to 12.72), and with stroke in women (OR 3.20, 95% CI 1.04 to 10.54) but not in men (OR 1.37, 95% CI 0.38 to 3.88). In conclusion, in the United States population, increased leptin concentrations are significantly associated with MI/stroke in men and women independently of traditional cardiovascular risk factors and obesity status.

We thank Dr. Kuwada for the comments related to our study and are pleased to provide specific answers below. Prevalence and Type of Sleep Disordered Breathing in Patients Post Acute Myocardial Infarction: We fully agree that the polygraphy device used in our study does not necessarily allowdifferentiation between obstructive and central sleep disordered breathing (SDB) events. Therefore, we used the overall apnea–hypopnea index, without specific subanalysis for obstructive and central events. Indeed, we specifically note the inability to discriminate between obstructive and central events as a significant limitation of our study.

Introduction: Obesity is linked with heightened vulnerability to cardiovascular diseases including hypertension. Nonetheless, mechanistic studies addressing the effects of experimental weight gain on blood pressure are lacking. We sought to examine whether experimental weight gain raises ambulatory blood pressure in healthy individuals and identify any relationship between changes in blood pressure and changes in regional fat distribution. Methods: Twenty-six normal weight subjects were randomized to a 8-week period of weight gain through overfeeding (N=16; age 30.4±6.6 years, BMI 23.5±3.5 kg/m 2 ) or weight maintenance (N=10; age 27.1±7.7 years, BMI 23.6±2.7 kg/m 2 ). Measurements of body composition by dual-energy X-ray absorptiometry and abdominal computed tomographic scans and 24-h ambulatory blood pressure monitoring were obtained at baseline and at follow-up. Results: Overfeeding resulted in an increase in body weight of 3.7±1.5 kg ( p p 2 , p =0.002) and subcutaneous fat (135.5±77.4 to 167.9±82.9 cm 2 , p p =0.009) and mean blood pressure (MAP) (85.1±4.9 to 86.8±5.1 mmHg, p =0.02), while blood pressure was unchanged in controls. Changes in MAP were positively correlated only with changes in visceral fat (rho=0.452, p =0.02) but not with changes in weight or any other body composition measure. Conclusion: Modest weight gain leads to marked elevation in 24-h blood pressure in lean healthy subjects. The association between increased MAP and abdominal visceral fat accumulation suggests that visceral deposition of adipose tissue may contribute specifically and mechanistically to the enhanced risk of hypertension associated with weight gain.

While sleep apnea (SA) might be a modifiable cardiovascular risk factor, recent data suggest that SA is severely underdiagnosed in patients after acute myocardial infarction (MI). There is limited evidence about day-night variation of onset of MI on dependence of having SA. We therefore investigated the prevalence of SA and examined the day-night variation of onset of MI in acute MI patients.We prospectively studied 782 consecutive patients admitted to the hospital with the diagnosis of acute MI. All subjects underwent sleep evaluations using a portable device after at least 48 h post-admission. Using the apnea-hypopnea index (AHI), groups were defined as patients without SA (5 events/h), mild SA (5-15 events/h), moderate SA (15-30 events/h), and severe SA (≥ 30 events/h).Almost all patients (98%) underwent urgent coronary angiography and 91% of patients underwent primary PCI. Using a threshold of AHI ≥ 5 events/h, SA was present in 65.7% of patients after acute MI. Mild SA was present in 32.6%, moderate in 20.4% and severe in 12.7%. The day-night variation in the onset of MI in all groups of SA patients was similar to that observed in non-SA patients. From 6 AM to 12 PM, the frequency of MI was higher in both SA and non-SA patients, as compared to the interval from 12 AM to 6 AM (all p0.05).There is a high prevalence of SA in patients presenting with acute MI. Peak time of MI onset in SA patients was between 6 AM and noon, similar to that in the general population. Whether diagnosis and treatment of SA after MI will significantly improve outcomes in these patients remains to be determined.

Rationale: The link between obesity, hyperleptinemia, and development of cardiovascular disease is not completely understood. Increases in leptin have been shown to impair leptin signaling via caveolin-1–dependent mechanisms. However, the role of hyperleptinemia versus impaired leptin signaling in adipose tissue is not known. Objective: To determine the presence and significance of leptin-dependent increases in adipose tissue caveolin-1 expression in humans. Methods and Results: We designed a longitudinal study to investigate the effects of increases in leptin on adipose tissue caveolin-1 expression during weight gain in humans. Ten volunteers underwent 8 weeks of overfeeding, during which they gained an average weight of 4.1±1.4 kg, with leptin increases from 7±3.8 to 12±5.7 ng/mL. Weight gain also resulted in changes in adipose tissue caveolin-1 expression, which correlated with increases in leptin (rho=0.79, P =0.01). In cultured human white preadipocytes, leptin increased caveolin-1 expression, which in turn impaired leptin cellular signaling. Functionally, leptin decreased lipid accumulation in differentiating human white preadipocytes, which was prevented by caveolin-1 overexpression. Further, leptin decreased perilipin and fatty acid synthase expression, which play an important role in lipid storage and biogenesis. Conclusions: In healthy humans, increases in leptin, as seen with modest weight gain, may increase caveolin-1 expression in adipose tissue. Increased caveolin-1 expression in turn impairs leptin signaling and attenuates leptin-dependent lowering of intracellular lipid accumulation. Our study suggests a leptin-dependent feedback mechanism that may be essential to facilitate adipocyte lipid storage during weight gain.

Background: Normal weight adults gain leg fat gain via adipocyte hyperplasia and upper body subcutaneous (UBSQ) fat gain via adipocyte hypertrophy. Objective: To understand whether regional fat loss mirrors fat gain and whether leg fat loss results in decreased adipocyte number vs. size. Design: We assessed UBSQ, leg and visceral fat gain and loss in response to over- and underfeeding in 23 young, healthy normal weight adults (15 men). Participants gained ∼5% weight over 8 weeks and lost ∼80% of gained fat over the following 8 weeks. We measured abdominal subcutaneous and femoral adipocyte size and number after weight gain and loss. Results: Volunteers gained 3.1 ± 2.1 kg of body fat with overfeeding and lost 2.4 ± 1.7 kg with calorie restriction. Although upper body subcutaneous (UBSQ) fat and visceral fat gains were completely reversed with weight loss, leg fat had not yet returned to baseline values by 8 weeks. Abdominal and femoral adipocyte size decreased significantly with weight loss, but the number of adipocytes did not decrease. Abdominal adipocyte size decreases correlated (rho= 0.76, p = 0.001) with UBSQ fat mass decreases and femoral adipocyte size decreases correlated (rho= 0.49, p=0.05) with leg fat mass decreases. Conclusion: UBSQ and visceral fat depots increase and decrease proportionately with short term weight gain and loss, whereas gain and loss of leg fat are less well linked. Loss of lower body fat is due to reduced fat cell size, not number, which may result in long-term increases in leg fat cell number. This may have implications for long-term weight control.

Background An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF. Methods We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB. Results Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m 2 , and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low ( R 2 = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively. Conclusions Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment.

Obesity has been associated with increased cardiac sympathetic activation during wakefulness, but the effect on sleep-related sympathetic modulation is not known. The aim of this study was to investigate the effect of fat gain on cardiac autonomic control during wakefulness and sleep in humans. We performed a randomized, controlled study to assess the effects of fat gain on heart rate variability. We recruited 36 healthy volunteers, who were randomized to either a standardized diet to gain ≈4 kg over 8 weeks followed by an 8-week weight loss period (n=20) or to serve as a weight-maintainer control (n=16). An overnight polysomnogram with power spectral analysis of heart rate variability was performed at baseline, after weight gain, and after weight loss to determine the ratio of low-frequency to high-frequency power and to examine the relationship between changes in heart rate variability and changes in insulin, leptin, and adiponectin levels. Mean weight gain was 3.9 kg in the fat gain group versus 0.1 kg in the maintainer group. Low frequency/high frequency increased both during wakefulness and sleep after fat gain and returned to baseline after fat loss in the fat gain group and did not change in the control group. Insulin, leptin, and adiponectin also increased after fat gain and fell after fat loss, but no clear pattern of changes was seen that correlated consistently with changes in heart rate variability. Short-term fat gain in healthy subjects is associated with increased cardiac sympathetic activation during wakefulness and sleep, but the mechanisms remain unclear.

Impaired brachial flow-mediated dilation (FMD) is associated with risk for subsequent cardiovascular events in patients after myocardial infarction (MI). These patients often have obstructive sleep apnea (OSA). We tested the hypothesis that patients with OSA post MI will exhibit more severe impairment in FMD.We studied 64 patients with MI admitted to our hospital. OSA was determined using polysomnography. FMD was measured using high-resolution ultrasonography, with researchers blind to the OSA diagnosis.The mean age was 60 ± 11 years, and the mean BMI was 29 (26, 32 kg/m(2)), 84% of patients were men, 39% had moderate to severe OSA (apnea-hypopnea index [AHI]15), and 31% of the patients had mild OSA (5 ≤ AHI15). FMD was severely impaired in patients with moderate to severe OSA (0.8% ± 0.7%) as compared with patients without OSA (4.7% ± 0.8%, P = .001) and with mild OSA (3.9% ± 0.8%, P = .015). Linear regression showed that FMD was associated with log nocturnal nadir oxygen saturation (minSaO(2)) (β = 31.17, P = .0001), age (β = -0.11, P = .006). MinSaO(2) was an independent predictor of FMD after adjustment for possible confounders (β = 26.15, P = .001).FMD is severely impaired in patients with moderate to severe OSA post MI, which may be partially related to nocturnal hypoxemia. Patients with OSA may, therefore, be at higher risk for subsequent cardiovascular events after an MI. Identifying and treating OSA may have important implications in the long-term prognosis of patients post MI. Further studies are necessary to determine if the presence of OSA would affect the long-term occurrence of cardiovascular events after an MI.

TO THE EDITOR: Obstructive sleep apnea (OSA) is highly prevalent in the general population and has been associated with arrhythmias, hypertension, stroke, and heart failure (1). Identification of OSA in cardiovascular patients is especially important as untreated OSA may be accompanied by increased cardiovascular events, and this risk may be attenuated by treatment with continuous positive airway pressure (CPAP)(2). We sought to investigate how the rates of recognition and diagnosis of obstructive sleep apnea compare to the actual prevalence of OSA in patients after myocardial infarction (MI). This study comprised two parts: a chart review of consecutive patients presenting with acute MI, and a prospective evaluation of MI patients who were recruited to undergo polysomnography. These studies were approved by the Institutional Review Board. First, we reviewed the medical records of 798 consecutive patients who were hospitalized with a diagnosis of acute MI between January and September 2007. Electronic records, including admission and dismissal notes were searched for diagnosed or suspected sleep disordered breathing, and especially for mention of OSA during the MI hospitalization. In the event of several hospital admissions for the same patient, only the first admission was used in our analysis. We further prospectively studied 74 patients who were hospitalized with acute myocardial infarction between 2004 and 2008, and were recruited to undergo attended overnight polysomnography, which is the gold standard in the diagnosis of OSA (Compumedics Siesta Wireless Sleep Recorder, Oxford Instruments, UK). All polysomnographies were performed within 6 weeks of the MI hospitalization, and scored by standard criteria (1). OSA was defined as present when the apnea hypopnea index (AHI) was >5. The diagnosis of MI was based on standard guidelines, and was made by the attending physicians who were blinded to this study. Patients were approached during their MI hospitalization, and their participation was based on their consent and availability of the study personnel and equipment. There was no systematic selection for specific demographic or patient characteristics. A review of electronic and paper records of these patients was also performed in similar fashion to that of the first part of our study. Between January and September 2007 there were 798 patients admitted to our institution with the diagnosis of acute MI. The mean age of this cohort was 69±14 years, and 512 (64%) were male. Diagnosed and suspected OSA was recorded in 97 (12%) patient records. The prospective cohort of 74 patients had a mean age of 62±13 years, and 46 (78%) were male. On review of their hospital records, 10 (14%) had documentation of diagnosed or suspected OSA. All of these patients underwent overnight polysomnography (PSG). For this group the mean AHI was 17±18 events/hour. OSA was present in 51 (69%), and severe OSA (AHI >15) in 30 (41%) patients. The main finding of this study was the low rate of documented or suspected OSA in patients hospitalized for acute MI, contrasting with the high prevalence of OSA in those in whom we conducted prospective PSG studies. This suggests a lack of awareness and recognition of OSA during treatment of acute MI. A high prevalence of OSA in the unselected general population has been well documented (1). Our results suggest that only 12 percent of patients hospitalized with acute MI had documentation of diagnosed or suspected OSA. When prospectively evaluated by overnight PSG a subgroup of patients had a much higher actual prevalence of OSA (over two thirds had at least mild OSA) but even in these patients with proven sleep apnea the possibility of OSA was documented in only 14 percent of patients. There are several limitations to our study. First, documentation in the medical record does not necessarily reflect the entire scope of medical evaluation; it is possible that in some patients OSA was suspected and they were verbally recommended to have an OSA evaluation which was not documented in the records, or this was left for a follow-up visit. Even so, it would be advantageous to arrange for screening for OSA during the hospitalization, just as we routinely initiate aspirin, beta-blocker, statin, and ACE inhibitor therapy before patient discharge. Cardiovascular disease patients with untreated severe OSA are thought to have worse cardiovascular outcomes (2,3), which may be improved with CPAP. Randomized controlled trials testing this assumption are lacking. Demonstrated beneficial effects of CPAP could lead to significant practice and guidelines changes. An absence of such clinical trials may help explain the relatively low awareness of OSA as an important consideration in the patient with MI.

We investigated breathing patterns and the occurrence of arrhythmias and ST-segment changes during sleep in patients with Brugada syndrome. Patients with Brugada syndrome are more likely to die from ventricular arrhythmias during sleep. ST-segment changes have been correlated with risk of sudden cardiac death. Whether sleep disturbances may contribute to arrhythmogenesis is unknown. Patients with Brugada syndrome underwent overnight polysomnography with simultaneous 12-lead electrocardiographic recording. A control group matched by age, gender, and body mass index (BMI) also underwent polysomnography. Twenty patients were included (50 ± 15 years old, 75% men). Despite their normal BMI (24.7 ± 2.7 kg/m 2 ), 45% had sleep-disordered breathing (SDB), with a mean apnea-hypopnea index of 17.2 ± 14 events/hour. In patients with a high risk of arrhythmias, 5 (63%) had SDB. In the control group, 27% had SDB. Atrial or ventricular arrhythmias were not observed. Spontaneous ST-segment changes occurred in 2 patients over 45 different time points. Most ST-segment changes were observed during rapid eye movement sleep (31%) or within 1 minute of arousals (44%). Regarding respiratory events, 25 (56%) of ST-segment changes were related to occurrence of apnea or hypopnea. In conclusion, patients with Brugada syndrome have a high prevalence of SDB even in the setting of normal BMI. The higher incidence of nocturnal death in patients with Brugada syndrome may be conceivably related to co-morbid SDB. Moreover, autonomic instability encountered in rapid eye movement sleep and arousals could potentiate the risk of arrhythmias.

Obstructive sleep apnoea (OSA) is a form of sleep disordered breathing with a high prevalence rate and is often underdiagnosed. OSA is associated with hypertension, coronary artery disease, stroke, peripheral vascular disease, heart failure, and arrhythmias. The presence of OSA may be a strong predictor of fatal cardiovascular events in patients with cardiovascular disease (CVD). Increased sympathetic drive, activation of metabolic and inflammatory markers, and impaired vascular function are some of the proposed mechanisms that could explain the association between OSA and cardiovascular diseases. Understanding these mechanisms is important for identifying treatment strategies. The presence of OSA should be considered in clinical practice, especially in patients with CVD. Randomized intervention studies are needed to establish whether early identification and treatment of OSA patients reduces cardiovascular morbidity.

Sympathetic hyperactivity is one of the mechanisms involved in the increased cardiovascular risk associated with depression, and there is evidence that antidepressants decrease sympathetic activity.We tested the following two hypotheses: patients with major depressive disorder with high scores of depressive symptoms (HMDD) have augmented muscle sympathetic nervous system activity (MSNA) at rest and during mental stress compared with patients with major depressive disorder with low scores of depressive symptoms (LMDD) and controls; sertraline decreases MSNA in depressed patients.Ten HMDD, nine LMDD and 11 body weight-matched controls were studied. MSNA was directly measured from the peroneal nerve using microneurography for 3 min at rest and 4 min during the Stroop color word test. For the LMDD and HMDD groups, the tests were repeated after treatment with sertraline (103.3 +/- 40 mg).Resting MSNA was significantly higher in the HMDD [29.1 bursts/min (SE 2.9)] compared with LMDD [19.9 (1.6)] and controls [22.2 (2.0)] groups (P = 0.026 and 0.046, respectively). There was a significant positive correlation between resting MSNA and severity of depression. MSNA increased significantly and similarly during stress in all the studied groups. Sertraline significantly decreased resting MSNA in the LMDD group and MSNA during mental stress in LMDD and HMDD groups. Sertraline significantly decreased resting heart rate and heart rate response to mental stress in the HMDD group.Moderate-to-severe depression is associated with increased MSNA. Sertraline treatment reduces MSNA at rest and during mental challenge in depressed patients, which may have prognostic implications in this group.

Obstructive sleep apnea (OSA) is highly prevalent in the United States, with an estimated 1 in 4 Americans at risk for OSA. In recent years, there has been a large body of work assessing the role of OSA as an independent risk factor for hypertension. Certain patient characteristics, such as age and the type of elevated blood pressure, may confer increased likelihood that the hypertension is secondary to underlying sleep apnea. Furthermore, early diagnosis and treatment of OSA may be beneficial in the management of hypertensive patients, particularly in those with poorly controlled hypertension. The focus of this brief review is on recent developments in the characteristics and treatment of sleep apnea-associated hypertension. Because of space limitations, only limited references are provided. The seventh report of the Joint National Committee identified OSA as an important identifiable cause of hypertension. As many as half of all patients with sleep apnea may have underlying hypertension, and many patients with hypertension, particularly resistant hypertension, may have OSA. In fact, there seems to be an interaction between OSA severity and resistance to antihypertensive medications.1 Elevated nocturnal blood pressure and reduced blood pressure “dipping” during sleep also suggest a higher likelihood of underlying sleep apnea, even in normotensive patients. Whether hypertension contributes to OSA remains unknown. OSA patients may not always exhibit elevated systolic pressures but may have a high prevalence of isolated diastolic hypertension.2–4 One study suggested that there was a significant association between the incidence of combined systolic and diastolic hypertension and the presence of sleep apnea in younger patients (

Background: Endothelial dysfunction assessed by flow mediated dilation (FMD) of the brachial artery has been identified as an independent predictor of cardiovascular events. However, whether weight gain impairs endothelial function is unknown. Methods: A randomized blinded controlled-trial to assess the effects of weight gain on endothelial function. After a weight maintenance period supervised by an experience dietitian, volunteers were randomized to gain weight (4 kg) or maintain weight. We recruited lean (BMI 18.5–24.9 kg/m 2 ) healthy volunteers (no diseases, medications and non-smokers) from the community. Using ultrasound, endothelial function was measured by FMD and non-flow mediated dilation (NFMD) of the brachial artery in the early morning (6:30 a.m.). Endothelial function was measured at baseline, after fat gain at 8 weeks and after weight loss at 16 weeks for fat-gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition techniques to measure body fat %, such as dual x-ray absorptiometry and abdominal CT scans were performed. Results: We recruited 35 fat-gainers and 8 weight maintainers. Mean age was 29 ± 6 years and 18 (42 %) were women. There were no differences in age, anthropometric and body composition measurements, blood pressure, heart rate or apnea hypopnea index at baseline between both groups. After an average gain of 4 kg, the fat-gainer group significantly increased their total, visceral and subcutaneous fat. Brachial artery FMD and NFMD remained unchanged in weight maintainers. However, it decreaed in fat-gainers (FMD=9.1 ± 3 vs. 7.6 ± 3.2, p=0.003 and NFMD=12.0 ± 4.9 vs. 10.1 ± 6.0, p=0.01), but recovered to baseline after subjects shed the gained weight (basleline vs. recovery: FMD=9.1 ± 3 vs. 9.0 ± 3, p=NS and NFMD =12.0 ± 4.9 vs.12.6 ± 5.0, p=NS). Visceral fat gain, but not subcutaneous fat gain was significantly correlated with the decrease in brachial artery FMD (rho =−0.42, p=0.004 and rho =−0.22, p=0.15, respectively). Conclusions: In lean healthy young subjects, modest weight gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial funcion recovers after weight loss. Viscerar rather than subcutaneous fat predicts endothelial dysfunction.

Recent studies have suggested that the apolipoprotein-B (apo-B)/apolipoprotein-AI (apo-AI) ratio predicts cardiovascular risk better than any of the cholesterol indexes. The aim of the present study was to assess if the apo-B/apo-AI ratio is related to the metabolic syndrome and its components. Data were analyzed from 2,964 subjects (mean age 48 years; 1,516 men, 1,448 women) from the National Health and Nutrition Examination Survey III with apolipoprotein data who were evaluated for the metabolic syndrome and its components. The metabolic syndrome was defined according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III and the International Diabetes Federation. The mean values of the apo-B/apo-AI ratio in subjects with and without the metabolic syndrome were compared. Overall, the median distribution of the apo-B/apo-AI ratio was significantly greater (p

To the Editor: In 1994, the Centers for Disease Control and Prevention conducted a study evaluating retired National Football League (NFL) players. Linemen were 3 times more likely than other position players to die of heart disease and had a 52% higher risk of cardiovascular death than the

Hypertension is a notoriously complex disease, with a mosaic of potential interactive etiologies. Age, gender, nutrition, environment, stress, obesity, and genetics have been cited as causal factors, as has been dysfunction in renal, endocrine, and neural circulatory control mechanisms. More recently, the epidemic of obesity has prompted recognition of an interaction between obstructive sleep apnea and increased blood pressure. This has, in turn, provided an exciting opportunity for more comprehensive understanding of the pathophysiological mechanisms and potential treatment strategies for hypertensive patients. Both hypertension and obstructive sleep apnea (OSA) are each increasingly common. Hypertension is present in well over a third of middle-aged subjects, and sleep apnea is reported to be present in 25% of middle-aged men and 10% of middle-aged women.1 Other common characteristics of hypertension and OSA include their association with obesity and male gender. Furthermore, both conditions are often clinically undiagnosed and may be accompanied by increased risk of cardiac and vascular damage. Although hypertension and OSA are common in the general population, epidemiological studies suggest that their comorbid prevalence exceeds strikingly that which would be anticipated to occur by chance alone. These observations, based on cross-sectional data, have been further strengthened by prospective studies demonstrating that increasing severity of OSA is a risk factor for the development of incident hypertension over 4 years.2 This etiologic interaction is …

Observational data suggest sudden cardiac death is more likely to occur during sleep in patients with obstructive sleep apnea (OSA). Sleep-related autonomic abnormalities may be implicated. We hypothesized that the presence of OSA is associated with increased cardiac sympathetic drive during sleep in patients after myocardial infarction (MI). We conducted a cross-sectional study of patients (n=40) within 1 to 3 months after MI. The presence of OSA was determined by polysomnography. Spectral analysis was performed 5-minute periods of stable ventilation during both REM sleep and non-REM sleep (stage 3 and 4). The LF/HF ratio was calculated to reflect sympathovagal balance. Mean age of study participants was 58±10 years, 83% were men and 95% were taking β-blockers. OSA was present in 60% of the patients. The LF/HF ratio was higher in patients with OSA during both non-REM (6.5±7.6 vs. 2.7±1.8, p=0.02) and REM sleep (6.4±5.4 vs. 3.9±3.3, p=0.03). OSA is accompanied by an altered cardiac sympathovagal balance favoring heightened sympathetic drive during both non-REM and REM sleep in patients after MI. This might contribute to the increased risk of sudden cardiac death during sleep in patients with OSA, and may be associated with poorer prognosis in this patient population.