The Human Endogenous Circadian System Causes Greatest Platelet Activation during the Biological Morning Independent of Behaviors

Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM), potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01). These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian influences on platelet function could contribute to the morning peak in adverse cardiovascular events as seen in many epidemiological studies

The Impact of Educational Attainment on Observed Race/Ethnic Disparities in Inflammatory Risk in the 2001–2008 National Health and Nutrition Examination Survey

Inflammation has shown to be an independent predictor of cardiovascular disease (CVD) and growing evidence suggests Non-Hispanic Blacks (NHBs) and certain Hispanic subgroups have higher inflammation burden compared to Non-Hispanic Whites (NHWs). Socioeconomic status (SES) is a hypothesized pathway that may account for the higher inflammation burden for race/ethnic groups yet little is known about the biological processes by which SES “gets under the skin” to affect health and whether income and education have similar or distinct influences on elevated inflammation levels. The current study examines SES (income and education) associations with multiple levels of C-Reactive Protein (CRP), an important biomarker of inflammation, in a sample of 13,362 NHWs, 7696 NHBs and 4545 Mexican Americans (MAs) in the United States from the 2001 to 2008 National Health and Nutrition Examination Survey. After adjusting for age, sex, and statin use, NHBs and MAs had higher intermediate and high CRP levels compared to NHWs. Income lessened the magnitude of the association for both race/ethnic groups. The greater intermediate and high CRP burden for NHBs and MAs was strongly explained by educational attainment. MAs were more vulnerable to high CRP levels for the lowest (i.e., less than nine years) and post high school (i.e., associates degree) educational levels. After additional adjustment for smoking, heavy drinking, high waist circumference, high blood pressure, diabetes and statin use, the strength of the association between race/ethnicity and inflammation was reduced for NHBs with elevated intermediate (RR = 1.31; p ≤ 0.001) and high CRP levels (RR = 1.14; p ≤ 0.001) compared to NHWs but the effect attenuated for MAs for both intermediate (RR = 0.74; p ≤ 0.001) and high CRP levels (RR = 0.38; p ≤ 0.001). These findings suggest educational attainment is a powerful predictor of elevated CRP levels in race/ethnic populations and challenges studies to move beyond examining income as a better predictor in the SES-inflammation pathway

The role of prenatal food insecurity on breastfeeding behaviors: Findings from the United States pregnancy risk assessment monitoring system

Background In addition to its health and nutritional benefits, breastfeeding can save low-income, food insecure mothers the cost of infant formula so that money can be spent on food and other necessities. Yet breastfeeding may exacerbate food insecurity by negatively affecting maternal employment. The relationship between food insecurity and breastfeeding has been explored previously, with varying results. The purpose of this study was to determine the relationship between prenatal food insecurity and breastfeeding initiation and early cessation (\u3c 10 weeks) among U.S. mothers. Methods Data were pooled from 2012 to 2013 (Phase 7) of the Pregnancy Risk Assessment Monitoring System, a population-based cross-sectional survey of postpartum women administered 2–4 months after delivery. The analytic sample was drawn from Colorado, Maine, New Mexico, Oregon, Pennsylvania, and Vermont, and limited to mothers aged 20 years and older whose infants were alive and living with them at the time of the survey (n = 10,159). We used binomial and multinomial logistic models to assess the predictive association between food insecurity and breastfeeding initiation and early cessation, respectively, while controlling for confounders. Results Most women reported prenatal food security (90.5%) and breastfeeding initiation (91.0%). Of those who initiated breastfeeding, 72.7% breastfed for \u3e 10 weeks. A larger proportion of food secure women compared to food insecure women, initiated breastfeeding (91.4% vs. 87.6%, P \u3c 0.01), and patterns of early breastfeeding cessation differed significantly between the two groups (P \u3c 0.01). In the final models, prenatal food insecurity was not associated with breastfeeding initiation or early cessation, with one exception. Compared to food secure mothers, mothers reporting food insecurity had a lower risk of breastfeeding for 4–6 weeks than for \u3e 10 weeks, independent of covariates (relative risk ratio 0.65; 95% CI 0.50, 0.85; P \u3c 0.01). Women who were married, had a college degree, and did not smoke were more likely to initiate breastfeeding and breastfeed for a longer time, regardless of food security status (P \u3c 0.01). Conclusions Socioeconomic, psychosocial, and physiological factors explain the association between prenatal food insecurity and breastfeeding outcomes among this U.S. sample. More targeted and effective interventions and policies are needed to encourage the initiation and duration of breastfeeding, regardless of food security status

The Human Endogenous Circadian System Causes Greatest Platelet Activation during the Biological Morning Independent of Behaviors

Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM), potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise. METHODOLOGY/PRINCIPAL FINDINGS: We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01). These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors. CONCLUSIONS/SIGNIFICANCE: These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian influences on platelet function could contribute to the morning peak in adverse cardiovascular events as seen in many epidemiological studies

Protocol.

<p>Rasterplot, including two baseline days, twelve 20-h cycles, and discharge day of an example subject with a habitual bedtime of midnight. Blue bars, baseline and discharge wake episodes in normal room light (∼90 lux); solid back bars, scheduled sleep (0 lux); gray bars, wake episodes in dim light (∼1.8 lux); red bars, timing of the test batteries; dotted line illustrates the circadian core body temperature minimum throughout the protocol, with an average circadian period of 24.09h in these subjects. Each test battery consisted of a mental, tilt, and exercise stress (S) test, each preceded and followed by a baseline (B) and recovery (R) episode. The timing of the blood draws is indicated as red filled circles.</p

Endogenous circadian rhythms in platelet function from cosinor analyses.

<p>Endogenous circadian rhythms in platelet function from cosinor analyses.</p

Independent influence of behavioral stressors on platelet function.

<p>WBA, platelet count, and plasma epinephrine were increased by each of the three stressors, with a (partial) recovery during recovery. In contrast, while the platelet surface markers showed a gradual increase across the approximately 3-h test battery, there was no consistent increase and recovery caused by the three stressors. Mental, mental stress test; tilt, passive head up tilt table test; exercise, cycle exercise test; B, baseline; S, stress test; R, recovery; x-axes, minutes from first blood sample within test battery; left y-axes, absolute values; right y-axes, data expressed as a percentage of each individual’s mean values across the forced desynchrony protocol; error bars, SEM; P-values, significance for effect of time across full stress test battery (9 time points); *, significance for change between consecutive samples (from baseline to stress test and from stress test to recovery). Note platelet ATP release is not shown (see above text).</p