Anna Svatikova

Independent Association Between Plasma Leptin and C-Reactive Protein in Healthy Humans

Background—C-reactive protein (CRP) is synthesized from the liver and is regulated by cytokines, especially interleukin-6. Leptin, the adipocyte-derived protein product of the ob gene, is related to amount of body fat. The long form of the leptin receptor resembles cytokine receptors, which include the interleukin-6 receptor. Both leptin and CRP may be increased in women, in obesity, and in inflammation, and both have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk. We tested the hypothesis that leptin is associated with CRP levels independently of the influences of gender, body mass index (BMI), waist-to-hip ratio, and other variables. Methods and Results—We studied 100 healthy volunteers (48 men, and 52 women). For all subjects, leptin was independently associated with CRP after adjustment for age, gender, BMI, waist-to-hip ratio, smoking, and alcohol consumption (F=12.39, P =0.0007). There was a strong and significant positive relationship between leptin and CRP in both women (R =0.61, P <0.0001) and men (R =0.55, P <0.0001) considered separately. The association between leptin and CRP was significant even after adjustment for age, BMI, waist-to-hip ratio, smoking, and alcohol consumption in women (F=7.13, P =0.01) and men (F=5.69, P =0.02). When only subjects with BMI <25 kg/m2 were considered (n=47), CRP was not linked to BMI (R =0.02, P =0.96), but a significant association between leptin and CRP was still evident (R =0.55, P <0.0001). Conclusions—Leptin and CRP levels are independently associated in normal humans, providing further evidence linking metabolic and inflammatory cardiovascular disease mechanisms.

Positional therapy in ischemic stroke patients with obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) is common in stroke patients and is associated with poor functional outcome. The effects of positional therapy in ischemic stroke patients with OSA have not been investigated. We tested the hypothesis that ischemic stroke patients have less severe OSA during positional therapy that promotes nonsupine positioning. METHODS We conducted a randomized, controlled, cross-over study. Sleep apnea screening studies were performed on two consecutive nights, using a portable respiratory monitoring system, on 18 subjects within the first 14days of ischemic stroke. An apnea-hypopnea index (AHI) ⩾5 established the diagnosis of OSA. Subjects were randomized to positional therapy that included the use of a therapeutic pillow on either the first or second night. On the control night, subjects used the hospital pillow and were positioned ad lib. Treatment effect on AHI was estimated using a repeated measures model. RESULTS All ischemic stroke subjects studied had OSA. The predominantly male group had a median age of 58years, BMI of 29kg/m(2), NIH Stroke Scale score of 3, and a median AHI on the nontherapeutic night of 39 (interquartile range: 21-54). Positional therapy reduced the amount of supine positioning by 36% (95% CI: 18-55% (P<0.001)). The AHI was reduced by 19.5% (95% CI: 4.9-31.9% (P=0.011)), when using positional therapy compared to sleeping ad lib. CONCLUSIONS Positional therapy to avoid supine positioning modestly reduces sleep apnea severity after ischemic stroke, and may therefore improve outcomes.

Sleep apnea treatment after stroke (SATS) trial: Is it feasible?

Sleep apnea affects more than half of patients with acute ischemic stroke and is associated with poor stroke outcome. This pilot study assessed the feasibility of a randomized, sham-controlled continuous positive airway pressure (CPAP) trial in subjects with acute ischemic stroke. Subjects identified with sleep apnea based on an apnea-hypopnea index≥5 on overnight polysomnography or portable respiratory monitoring within 7 days of onset of stroke symptoms were randomized to receive active or sham CPAP for a 3-month period. Objective usage was ascertained by compliance data cards. Subjects, treating physicians, and outcome assessors were masked to intervention allocation. Among 87 subjects who provided consent, 74 were able to complete sleep apnea screening, 54 (73%) of whom had sleep apnea. Thirty-two subjects agreed to randomization. Of the 15 subjects who commenced active titration, 11 (73%) took the device home, and 8 (53%) completed the 3-month follow-up. Of the 17 subjects who commenced sham titration, 11 (65%) took the sham device home and completed the 3-month follow-up. The median cumulative usage hours over the 90 days were similar in the active group (53 hours; interquartile range, 22-173 hours) and the sham group (74 hours; interquartile range, 17-94 hours), and blinding to subject condition was successfully maintained. This first-ever randomized, sham-controlled trial of CPAP in patients with recent stroke and sleep apnea demonstrates that sham treatment can be an effective placebo.

A Randomized Trial of Cardiovascular Responses to Energy Drink Consumption in Healthy Adults

Author Affiliations: Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston, Massachusetts (Sammon, Trinh); VUI Center for Outcomes Research, Analytics and Evaluation, Henry Ford Health System, Detroit, Michigan (Abdollah, Menon); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (Choueiri, Kantoff); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (Nguyen).

The Challenges of Prevention, Diagnosis and Treatment of Ischemic Heart Disease in Women.

Increasing evidence suggests that there are significant differences in the presentation, diagnosis and treatment of ischemic heart disease in women compared to men. Women often present with atypical symptoms, and this, in association with a consistent underestimation of their risk for ischemic heart disease, leads to underdiagnosis and undertreatment in women. Cardiovascular risk factors unique to women have only recently been recognized, and moreover, traditional risk factors have recently been shown to have greater impacts on women. Consequently, women suffer more disability and poorer clinical outcomes, with higher cardiovascular morbidity and mortality. These discrepancies may in part be secondary to the higher prevalence of nonobstructive coronary artery disease in women with persistent chest pain symptoms as compared to men when evaluated invasively. Focused diagnostic and therapeutic strategies unique to women are thus needed, but unfortunately, such sex-specific guidelines do not yet exist, largely due to lack of awareness, both on the part of providers and patients, as well as a paucity of evidence-based research specific to women. Although underutilized in women, diagnostic modalities, including functional and anatomic cardiac tests as well as physiologic assessments of endothelial and microvascular function, are useful for establishing the diagnosis and prognosis of suspected ischemic heart disease in women. This review discusses the current challenges of prevention, diagnosis and treatment of ischemic heart disease in women.

EXPERIMENTAL SLEEP RESTRICTION INCREASES NOCTURNAL BLOOD PRESSURE AND ATTENUATES BLOOD PRESSURE DIPPING IN HEALTHY INDIVIDUALS

Although growing evidence suggests that insufficient sleep is linked to enhanced risk of adverse events including hypertension, mechanistic investigations supporting causal relationships are lacking. In this study we sought to evaluate changes in ambulatory blood pressure in healthy individuals

Echocardiographic findings in ischemic stroke patients with obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) has been associated with cardiac abnormalities. Whether any cardiac dysfunction is present in ischemic stroke patients with OSA is not known. The purpose of this study was to compare echocardiographic findings in ischemic stroke patients with and without OSA. METHODS Nocturnal polysomnography was performed on 28 ischemic stroke subjects within 7 days of symptom onset. OSA was defined as an apnea-hypopnea index of ≥10. Echocardiographic variables were compared between the OSA and non OSA groups using Wilcoxon signed-rank, chi-square, or Fishers exact tests. RESULTS The 14 (50%) subjects with OSA had comparable cardiac function and structure to those without OSA (n=14). Left ventricular (LV) mass index, LV ejection fraction, LV diastolic function, left atrial area, and right ventricular systolic function were not different between groups. Ischemic stroke subjects, regardless of their OSA status, had LV diastolic dysfunction with preserved systolic function. CONCLUSIONS Subjects with and without OSA, based on polysomnography in the first 7 days after stroke, have comparable right and left ventricular function.

Cholesterol Management in the Era of PCSK9 Inhibitors

Purpose of ReviewCholesterol management in the current era is discussed. Aggressive reduction of low density lipoprotein (LDL) cholesterol plays a key role in primary and secondary prevention of heart disease. Statins are the recommended first-line therapy in patients with hyperlipidemia; however, additional complementary approaches are frequently needed for patients who fail to reach their target LDL.Recent FindingsProprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that provide dramatic lowering of LDL and promise outcome benefit. Despite great enthusiasm about their cardiovascular benefit, concerns have been raised regarding their cost and added value to the healthcare system. Although cost-effectiveness studies have yielded inconclusive results, analyses suggest that the current cost of PCSK9 inhibitors is disproportionately high and must be significantly reduced to add positive net benefit to healthcare system.SummaryPCSK9 inhibitors significantly lower LDL cholesterol. Further outcome data and cost-effectiveness analyses are needed to overcome the current barriers with PCSK9 inhibitors that patients, physicians, and payers face.

Hemodynamic Responses to Energy Drink Consumption—Reply

Hemodynamic Responses to Energy Drink Consumption To the Editor Dr Svatikova and colleagues1 investigated acute cardiovascular responses in healthy adults 30 minutes after ingestion of an energy drink (containing 62 g of sugar, caffeine, and taurine) compared with a placebo drink (containing approximately 62 g of sugar but no caffeine or other stimulants). In addition, the authors investigated the cardiovascular response of energy drink consumption during mental and physical stress tests. They observed that blood pressure was significantly higher after consumption of the energy drink compared with placebo, and that both drinks raised heart rate to similar levels. We would like to underscore some important limitations of the study regarding the duration of the postdrink period and the design and methods used. Two studies from our laboratory measured blood pressure and heart rate using beat-to-beat technology over longer postdrink periods (ie, 80 minutes2 or 120 minutes2,3) and observed gradual increases over time with peak responses between 80 and 100 minutes after energy drink consumption. Therefore, the measurement of blood pressure and heart rate over a postdrink period of only 30 minutes underestimates the real hemodynamic effect of the energy drink. Moreover, Svatikova and colleagues1 performed stress tests within the ascending portion of the blood pressure and heart rate curves,2-4 potentially biasing their stress test results. The placebo drink used by Svatikova et al1 contained sugar that included glucose and fructose components known to affect resistance vessels and cardiac output in opposite directions (ie, decrease in total peripheral resistance and increase in cardiac output), potentially resulting in little or no effect on blood pressure.5 In our study5 investigating cardiovascular responses to sugary drinks, all 3 sugars (glucose, fructose, and sucrose) increased heart rate 60 minutes after ingestion. We believe the use of a sugar-sweetened placebo drink could have biased the heart rate response in the study by Svatikova and colleagues. When investigating cardiovascular responses to energy drink consumption, it seems more appropriate to use an inert placebo like water2,3 to fully capture the interaction between hemodynamically active components contained in an energy drink rather than a sugar-containing placebo.

POTENTIATED BLOOD PRESSURE RESPONSES TO ENERGY DRINK INTAKE IN CAFFEINE NAïVE HEALTHY ADULTS: A DOUBLE BLIND RANDOMIZED CONTROLLED STUDY

Energy drink consumption is widespread and rising among young adults. We and others have previously shown that energy drink consumption increases blood pressure, although the reported blood pressure increases among individuals are variable. Previous exposure to caffeine may be implicated in these