Cardiovascular Risk Factor, Circadian Dysregulation, Obesity
Conditions
Brief summary
A multidisciplinary investigation examining the circadian mechanisms regulating cardiovascular (CV) risk, with an additional focus on obesity. Specifically, in a valid circadian protocol, the investigators aim to study resting cardiovascular risk markers and the reactivity of circadian rhythms in these risk markers to standardized stressors. It is intended to compare results in lean and obese individuals to determine if there are specific risks across the circadian cycle specific to obesity. Furthermore, using an exploratory approach, the investigators propose to explore impairment in pre/post synaptic function in the cardiac left ventricle.
Detailed description
Overall, these studies will help us answer whether the circadian system predispose individuals to increased CV disease risk - particularly around the vulnerable morning period, and whether these risks differ with obesity. The results will serve as a foundation for clinical trials of appropriately timed dosing of medications targeting aspects of the CV system that increase effectiveness while decreasing side effects, and may have particular relevance to management of CV risk in people with obesity.
Interventions
COMBINATION_PRODUCTPositron Emission Tomography (PET) scanning of cardiac function at 3 time points across the 24 hour circadian cycle
Drugs are used for as part of physiological monitoring and not as interventions, including imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, and 11C-CGP12177).
Sponsors
Oregon Health and Science University
National Heart, Lung, and Blood Institute (NHLBI)
National Center for Advancing Translational Sciences (NCATS)
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Ages 25-65 * Lean and overweight (BMI 18.5-40kg/m2) * Habitually sedentary
Exclusion criteria
* History of smoking/tobacco use * Insomnia * Moderate to severe obstructive sleep apnea. * Prior shift work within 6 months prior to the study. * Prescription medications * Drugs of abuse * Acute, chronic, or debilitating medical condition (including diabetes, hypertension, and metabolic syndrome)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure (BP) | 5 Days | Measurements were collected up to 7 times per participant across the circadian cycle under constant conditions across 5 days. Resting BP and Exercise BP data were collected at the beginning of each of 7 wake periods in a supine position and where participants exercised at an intensity equivalent to brisk walking. Salivary melatonin was used to calculate the circadian phase marker using dim light melatonin onset (DLMO). All data were assigned a circadian phase relative to DLMO and binned into 4-hour (or 60-degree) intervals. In the statistical analysis, the weight group refers to normal or overweight, exercise condition refers to seated or exercising on the bike, and circadian phase refers to the center of the circadian bin. This is an observational study. Due to insufficient enrollment and an imbalanced group distribution, we do not have sufficient statistical power to fully interpret these data. The data are valuable as pilot data for future investigations and sample size estimation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Microvascular Blood Flux | 3 days | Coronary microvascular function, measured as coronary microvascular blood flux using myocardial contrast echocardiography. |
| Flow Mediated Dilation (FMD) | 5 days | FMD to measure endothelial function. |
| Heart Rate | 5 Days | Heart rate via 2-channel echocardiogram (ECG) |
| Epinephrine | 5 days | Venous Epinephrine to estimate sympathetic output |
| Norepinephrine | 5 days | Venous Norepinephrine to estimate sympathetic output |
| Cortisol | 5 days | Saliva cortisol to estimate sympathetic output |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSteven A Shea, PhD
Oregon Institute of Occupational Health Sciences
PRINCIPAL_INVESTIGATORJeanne M Link, PhD
OHSU Center for Radiochemistry Research
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 40.21 Years STANDARD_DEVIATION 14.2 |
| BMI | 21.94 kg/meter squared STANDARD_DEVIATION 1.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 5 |
| other Total, other adverse events | 5 / 12 | 3 / 5 |
| serious Total, serious adverse events | 0 / 12 | 0 / 5 |
Outcome results
None listed