Association between human papillomaviruses, metabolic syndrome, and all-cause death; analysis of the U.S. NHANES 2003-2004 to 2015-2016.

INTRODUCTION: Human papillomavirus (HPV) is the most common sexually transmitted infection, attributed to 4.5% of all cancers worldwide. Co-infection with the metabolic syndrome (MetS), a common cluster of cardiometabolic risk factors, has been shown to increase the persistence of HPV. The purpose of this study was to estimate the association between HPV and MetS on mortality risk. METHODS: Data for the current study was drawn from seven consecutive cycles (2003-2004 to 2015-2016) of the U.S. NHANES. The final analytic sample consisted of 5,101 individuals aged 18-65y with HPV and MetS information with follow-up to Dec. 31st, 2019. Baseline HPV status was assessed by either vaginal swab, penile swab or oral rinse and used to classify participants as: no HPV (n = 1,619), low (n = 1,138), probable (n = 672), and high-risk (n = 1,672; 22% type 16, and 10% type 18) HPV using IARC criteria. MetS was assessed by the Harmonized criteria. RESULTS: The average follow-up was 9.4 y with 240 all-cause deaths (no HPV: n = 46 deaths; low-risk: n = 60 deaths; probable: n = 37 deaths, and; high-risk: n = 97 deaths). HPV status alone revealed no associations with mortality in fully adjusted models. Cross-classification into discrete MetS/HPV strata yielded an increased risk of mortality in females with high-risk HPV/MetS relative to the no MetS/no HPV group. CONCLUSIONS: In this study, low, probable, and high-risk HPV and MetS were differentially related to mortality risk in men and women. Further work is necessary to separate the temporal, age, vaccination, and sex effects of HPV diagnosis in these relationships using prospective studies with detailed histories of HPV infection and persistence.

Changes in the prevalence of U.S. adults using diet, exercise, pharmaceuticals and diet products for weight loss over time: Analysis of NHANES 1999-2018.

To examine changes in the use of diet, exercise, and pharmacological/diet product weight loss (WL) practices over time, and differences in these trends by sex and obesity status, data from the National Health and Examination Survey (NHANES Continuous 1999-2018) was used. The prevalence of diet, exercise and use of WL drugs and products over time were examined in men and women with and without obesity in a series of cross-sectional nationally representative samples (n = 43,020). Women and those with obesity were more likely to engage in WL practices over the past year, with an increased prevalence of WL efforts over time (38.4 to 43.2%). Amongst those who engaged in WL attempts, diet-related WL was most common (87-93%), followed by exercise-related WL (47-68%), whereas use of WL drugs and products was the least common (5-21%). There were modest differences in the prevalence of diet or exercise WL over time, with some differences by sex and obesity status. Most notable was the increase in the prevalence of exercise WL practices in women with obesity, with no differences among men or women without obesity. When examining specific types of diets, there were more clear differences in the adoption of diets over time, with the use of more traditional calorie/portion/fat restriction diets becoming less prevalent, and sugar/carbohydrate restriction becoming more prevalent over time (P<0.005). Changes over time in the use of diets were, were however, similar in men and women with and without obesity. Use of pharmacotherapy/diet products tended to decline in prevalence over time but was consistently highest in women with obesity. Thus, there are differences in the types of WL strategies individuals have employed over time, with variations in their popularity of use by sex and obesity status. However, the pattern of changes over time were quite similar in men and women with and without obesity.

The relationships between acetylcholine-induced chest pain, objective measures of coronary vascular function and symptom status.

Background: Acetylcholine-induced chest pain is routinely measured during the assessment of microvascular function. Aims: The aim was to determine the relationships between acetylcholine-induced chest pain and both symptom burden and objective measures of vascular function. Methods: In patients with angina but no obstructive coronary artery disease, invasive studies determined the presence or absence of chest pain during both acetylcholine and adenosine infusion. Thermodilution-derived coronary blood flow (CBF) and index of microvascular resistance (IMR) was determined at rest and during both acetylcholine and adenosine infusion. Patients with epicardial spasm (>90%) were excluded; vasoconstriction between 20% and 90% was considered endothelial dysfunction. Results: Eighty-seven patients met the inclusion criteria. Of these 52 patients (60%) experienced chest pain during acetylcholine while 35 (40%) did not. Those with acetylcholine-induced chest pain demonstrated: (1) Increased CBF at rest (1.6 ± 0.7 vs. 1.2 ± 0.4, p = 0.004) (2) Decreased IMR with acetylcholine (acetylcholine-IMR = 29.7 ± 16.3 vs. 40.4 ± 17.1, p = 0.004), (3) Equivalent IMR following adenosine (Adenosine-IMR: 21.1 ± 10.7 vs. 21.8 ± 8.2, p = 0.76), (4) Increased adenosine-induced chest pain (40/52 = 77% vs. 7/35 = 20%, p < 0.0001), (5) Increased chest pain during exercise testing (30/46 = 63% vs. 4/29 = 12%, p < 0.00001) with no differences in exercise duration or electrocardiographic changes, and (6) Increased prevalence of epicardial endothelial dysfunction (33/52 = 63% vs. 14/35 = 40%, p = 0.03). Conclusions: After excluding epicardial spasm, acetylcholine-induced chest pain is associated with increased pain during exercise and adenosine infusion, increased coronary blood flow at rest, decreased microvascular resistance in response to acetylcholine and increased prevalence of epicardial endothelial dysfunction. These findings raise questions about the mechanisms underlying acetylcholine-induced chest pain.

Is anyone truly healthy? Trends in health risk factors prevalence and changes in their associations with all-cause mortality.

OBJECTIVE: The purpose of the study was to determine trends in the prevalence of individual health risk factors across time and to examine if their associations with mortality have changed over time. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES III- 1988-1994 and NHANES 1999-2014; age ≥20 years) was used to examine differences in the odds ratio (OR) of 5-year mortality risk associated with various common health risk factors over the two survey periods using weighted logistic regression analysis adjusting for age, sex, obesity category and white ethnicity (n = 28,279). RESULTS: Over 97% of individuals had at least one of the 19 risk factors examined with no difference in the prevalence over time (P>0.34). The prevalence of lifestyle, social/mental and physical risk factors (2.2 to 19.1%) increased over time (P<0.0002), while the prevalence of having physiological risk factors decreased by ~6.5% (P<0.0001). Having any lifestyle or social/mental risk factor was significantly associated with a higher 5-year OR for mortality risk in 1999-2014, than 1988-94. In particular, having low education or use of mental health medication were not associated with mortality risk in 1988-94 (P>0.1), but were significantly associated with a higher 5-year OR for mortality in 1999-2014 (P<0.0001). Conversely, physiological risk factors were more weakly related with mortality risk in 1988-1994, than 1999-2014. Having any physical risk factor, and poor self-rated health were similarly related with 5-year mortality risk at both timepoints. CONCLUSION: Health risk factors have both increased and decreased in prevalence over time, along with changes in the association between many of the risk factors and mortality risk. Taken together, these changes complicate interpretation of temporal trends and warrant cautious interpretation of population health patterns based on surveillance data.

Neighborhood greenness, but not walkability, is associated with self-rated measures of health in older adults: An analysis of the Canadian Longitudinal Study on Aging.

The purpose of this analysis was to determine whether older Canadians residing in neighborhoods characterized by denser greenness or higher walkability have better self-reported health outcomes at 3-year follow-up. Data on self-reported chronic diseases (composite score of 10 conditions) and self-rated measures of health (general health, mental health, and healthy aging) from the Canadian Longitudinal Study on Aging (CLSA) were used as outcomes. The CLSA database was linked with the Canadian Active Living Environments (Can-ALE), a measure of walkability, and Normalized Difference Vegetation Index (NDVI), a measure of greenness. The analytic sample consisted of adults aged 65 and older (n = 15339, age 72.9 ± 5.6, 50 % female). Crude and adjusted associations were assessed using Poisson regression and proportional odds regression modelling. The 4th quartile of greenness was associated with the chronic disease index and all three measures of self-rated health (general health, mental health, and healthy aging); living in a neighborhood with the highest greenness was associated with better health three years later when compared to those in the lowest quartile of greenness. After adjustment for covariates of age, sex, income, education, and physical activity levels, only the association for the 3rd quartile of greenness was significantly associated with general health (OR: 0.90, 95 %CI: 0.81-0.99) and mental health (OR: 0.88, 95 %CI: 0.79-0.97). Can-ALE was not associated with any of the outcomes assessed. Future research assessing perceived environmental walkability and geriatric relevant health outcomes rather than chronic disease may provide greater insight into our understanding of age-friendly environments.

Inflammation, Oxidative Stress, and Antioxidant Micronutrients as Mediators of the Relationship Between Sleep, Insulin Sensitivity, and Glycosylated Hemoglobin.

Background: Sleep deprivation and poor sleep quality contribute to increases in oxidative stress, antioxidant imbalance, and a pro-inflammatory state which may predispose to a higher risk of diabetes. Our objective was to estimate the contributions of C-reactive protein (CRP), gamma glutamyl transferase (GGT), and micronutrient antioxidants (bilirubin, carotenoids, uric acid, vitamins A, C-E?) to the relationships between sleep-fasting insulin concentration and -glycosylated hemoglobin (HbA1c). Methods: Data from the 2005/06 US National Health and Nutritional Examination Survey were used (N = 1,946; 20 y+). Sleep quality and quantity was assessed by the Sleep Disorders Questionnaire, and fasting blood was collected to quantify CRP, GGT, antioxidant micronutrients, insulin concentration, and HbA1c. The bootstrap method was used to estimate the amount of mediation or contribution of these mediators to the sleep-insulin concentration and -HbA1c relationships, which were quantified as large (≥0.25) or moderate (≥0.09). Results: The sleep duration-fasting insulin relationship was mediated by GGT, carotenoids, uric acid, and vitamins C and D, whereas CRP and bilirubin were non-significant mediators of a moderate effect size. Similarly, the sleep quality-fasting insulin relationship was mediated by CRP, bilirubin and vitamin C, whereas GGT, carotenoids, uric acid, and vitamin D were non-significant large-to-moderate mediators. To a lesser degree, these micronutrients mediated for the relationship between sleep-HbA1c levels. Conclusion: Several factors related to inflammation, oxidative stress, and antioxidant status were found to lie on the pathway of the sleep-insulin and -glycemic control relationships. Sleep hygiene, reduced systemic inflammation/oxidative stress, and optimal antioxidants intake are potentially beneficial targets for managing diabetes risk.

Associations between weight discrimination and metabolic health: A cross sectional analysis of middle aged adults.

BACKGROUND: Concurrent with the recent rise in overweight and obesity, concerns with weight discrimination have arisen. Individuals who have experienced weight discrimination report a host of deteriorations related to physical and psychological health, which may co-exist with behaviours such as increased food consumption and decreases in physical activity that make weight management difficult. What remains less clear, however, is the extent to which metabolic health may be specifically affected, and how this may vary by setting and perceived intensity of the lifetime history of weight discrimination. METHOD: To address this, a secondary data analysis was performed on 1365 participants from year 25 of the Coronary Artery Disease in Young Adults (CARDIA) study who were living with overweight and obesity. Descriptive statistics and logistic regression analyses were performed on the presence of metabolic syndrome, diabetes, and abdominal obesity, as well as their experience of the weight discrimination. RESULTS: Prevalence of the metabolic syndrome, diabetes, and abdominal obesity was higher among those reporting low and high stress weight discrimination compared to those with no history of weight discrimination. In the adjusted analyses, weight discrimination was associated with a 65% greater likelihood for having metabolic syndrome, 85% greater likelihood of diabetes, and between a 2.5- and 3.9-times greater likelihood of abdominal obesity for low and high stress experiences, respectively. CONCLUSION: Exposure to weight discrimination may worsen metabolic health, as characterized by higher rates of metabolic syndrome and abdominal obesity. These associations may be greater with levels of stress experienced from weight discrimination. Further longitudinal work is necessary to understand the temporal sequence, time lag, and any possible critical periods for weight discrimination on metabolic health.

Concurrently Low Coronary Flow Reserve and Low Index of Microvascular Resistance Are Associated With Elevated Resting Coronary Flow in Patients With Chest Pain and Nonobstructive Coronary Arteries.

BACKGROUND: Coronary microvascular function can be distinctly quantified using the coronary flow reserve (CFR) and index of microvascular resistance (IMR). Patients with low CFR can present with low or high IMR, although the prevalence and clinical characteristics of these patient groups remain unclear. METHODS: One hundred ninety-nine patients underwent coronary microvascular assessments using coronary thermodilution techniques. A pressure-temperature sensor-tipped guidewire measured proximal and distal coronary pressure, whereas the inverse of the mean transit time to room temperature saline was used to measure coronary blood flow. The CFR and IMR were quantified during adenosine and acetylcholine hyperemia. RESULTS: Low adenosine and acetylcholine CFR was observed in 70 and 49 patients, respectively, whereas low CFR/low IMR to adenosine and acetylcholine was observed in 39(56%) and 19(39%) patients, respectively. Despite similar adenosine CFR, patients with low CFR/low IMR had increased resting (2.8±1.2 versus 1.3±0.4s-1) and hyperemic coronary blood flow (4.8±1.5 versus 2.1±0.5s-1) compared with patients with low CFR/high IMR (both P<0.01). The same pattern was observed in response to acetylcholine. Patients with low CFR/low IMR to adenosine were younger (56±12 versus 63±10 years), women (84% versus 66%), had fewer coronary risk factors (1.1±1.0 versus 1.6±1.1), lower hemoglobin A1c (5.8±0.7 versus 6.1±0.9 mmol/L), and thinner septal thickness (8.5±2.5 versus 9.9±1.6 mm) compared with patients with low CFR/high IMR to adenosine (all P<0.05). CONCLUSIONS: Low CFR/low IMR to adenosine and acetylcholine are associated with elevated resting coronary blood flow and preserved hyperemic coronary blood flow. These patients present with distinct phenotypic characteristics. Simultaneous CFR and IMR measures appear necessary to differentiate these endotypes.

Leisure sedentary time and physical activity are higher in neighbourhoods with denser greenness and better built environments: an analysis of the Canadian Longitudinal Study on Aging.

Associations of environmental variables with physical activity and sedentary time using data from the Canadian Longitudinal Study on Aging, and the Canadian Urban Environmental Health Research Consortium (Canadian Active Living Environments (Can-ALE) dataset, and Normalized Difference Vegetation Index (NDVI, greenness) dataset) were assessed. The main outcome variables were physical activity and sedentary time as measured by a modified version of the Physical Activity for Elderly Scale. The sample consisted of adults aged 45 and older (n = 36 580, mean age 62.6 ± 10.2, 51% female). Adjusted ordinal regression models consistently demonstrated that those residing in neighbourhoods in the highest Can-ALE category (most well-connected built environment) reported more physical activity and sedentary time. For example, males aged 75+ in the highest Can-ALE category had 2 times higher odds of reporting more physical activity (OR = 2.0, 95% CI = 1.1-3.5) and 1.8 times higher odds of reporting more sedentary time (OR = 1.8, 95% CI = 1.0-3.4). Neighbourhoods with higher greenness scores were also associated with higher odds of reporting more physical activity and sedentary time. It appears that an environment characterized by higher Can-ALE and higher greenness may facilitate physical activity, but it also facilitates more leisure sedentary time in older adults; research using device measured total sedentary time, and consideration of the types of sedentary activities being performed is needed. Novelty: Middle-aged and older adults living in neighbourhoods with higher Can-ALE scores and more greenness report more physical activity and leisure sedentary time Greenness is important for physical activity and sedentary time in middle-aged adults.

A systematic review and meta-analysis of the effect of treadmill desks on energy expenditure, sitting time and cardiometabolic health in adults.

BACKGROUND: As the health risks of sedentary working environments become more clear, greater emphasis on the implementation of walking interventions to reduce sitting time is needed. In this systematic review and meta-analysis, we investigate the role of treadmill-desk interventions on energy expenditure, sitting time, and cardiometabolic health in adults with sedentary occupations. METHODS: Relevant studies published in English were identified using CINAHL, EMBASE, MEDLINE, Web of Science, Scopus, and PubMed databases up to December 2020. Random effects meta-analysis models were used to pool study results. RESULTS: Thirteen relevant studies (six workplaces and seven laboratories) were found with a total of 351 participants. Pooled analysis of laboratory studies showed a significant increase in energy expenditure (105.23 kcal per hour, 95% confidence interval [CI]: 90.41 to 120.4), as well as metabolic rate (5.0 mL/kg/min, 95% CI: 3.35 to 6.64), among treadmill desk users compared to sitting conditions. No evidence of significant differences in blood pressure were found. In workplace studies, we observed a significant reduction in sitting time over a 24-h period (- 1.73 min per hour, 95% CI: - 3.3 to - 0.17) among users of treadmill desks, compared to a conventional desk. However, there were no evidence of statistically significant changes in other metabolic outcomes. CONCLUSIONS: Treadmill desks offer a feasible and effective intervention to increase energy expenditure and metabolic rate and reduce sitting time while performing work-related tasks. Future studies are needed to increase generalizability to different workplace settings and further evaluate their impact on cardiometabolic health.

Trends in Serum AST-to-ALT Ratio Among U.S. Adults: Analysis of the U.S. National Health and Nutrition Examination Survey.

Background: Using nationally representative data, we examined the age-, sex-, and ethnic-specific variation in the ratio of serum aspartate aminotransferase and alanine aminotransferase (AST-to-ALT ratio or AAR) of U.S. adults (20+ years). Understanding these subgroup differences in AAR will provide insight into population patterns of these ratios, which provide a basis for normative comparisons for the application of personalized diagnostic information to patients in the clinical setting. Methods: Data for this analysis are based on continuous cycles (1999-2016) of the National Health and Nutrition Examination Survey (NHANES). Results: Within the complete sample (n = 13,731), mean AST and ALT values were similar (∼25 U/L), with higher absolute values, but lower AAR, in males compared with females. From 1999-2000 to 2015-2016 there were consistent sex, age, and ethnic differences in the AAR. Specifically, the AAR for individuals 65+ years was markedly higher in all survey years, with subtle ethnic variation [Mexican Americans (0.95-1.04) Other Hispanic (1.0-1.09), Non-Hispanic White (1.05-1.11), Non-Hispanic Black (1.12-1.22), and Other Ethnicity (1.01-1.17)]. Sex-specific analysis reveals that the lower AAR observed among Mexican Americans is almost entirely accounted for by the markedly lower AAR in men. Conclusion: Future work is necessary to understand these subgroup variations in longer term studies with incident disease.

Associations between elevated kidney and liver biomarker ratios, metabolic syndrome and all-cause and coronary heart disease (CHD) mortality: analysis of the U.S. National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: We examined the relationship between ratios of select biomarkers of kidney and liver function on all-cause and coronary heart disease (CHD) mortality, both in isolation, and in combination with metabolic syndrome (MetS), among adults (20 + years, n = 10,604). METHODS: Data was derived from the U.S. National Health and Nutrition Examination Survey (1999-2016) including public-use linked mortality follow-up files through December 31, 2015. RESULTS: Select biomarker ratios of kidney (UACR or albuminuria and BUN-CR) and liver (AST-ALT and GGT-ALP) function in isolation and in combination with MetS were associated with all-cause and CHD mortality. Compared to individuals with neither elevated biomarker ratios nor MetS (HR = 1.00, referent), increased risk of all-cause mortality was observed in the following groups: MetS with elevated UACR (HR, 95% CI = 2.57, 1.99-3.33), MetS with elevated AST-ALT (HR = 2.22, 1.61-3.07), elevated UACR without MetS (HR = 2.12, 1.65-2.72), and elevated AST-ALT without MetS (HR = 1.71, 1.35-2.18); no other biomarker ratios were associated with all-cause mortality. For cause-specific deaths, elevated risk of CHD mortality was associated with MetS with elevated UACR (HR = 1.67, 1.05-2.67), MetS with elevated AST-ALT (HR = 2.80, 1.62-4.86), and elevated BUN-CR without MetS (HR = 2.12, 1.12-4.04); no other biomarker ratios were associated with CHD mortality. CONCLUSION: Future longitudinal studies are necessary to examine the utility of these biomarker ratios in risk stratification for chronic disease management.

Characterization of the Human Coronary Microvascular Response to Multiple Hyperaemic Agents.

BACKGROUND: It is unclear whether the coronary microvascular responses to multiple, mechanistically distinct hyperaemic agents exert similar dilatory responses or share common clinical predictors. This study therefore sought to characterize the index of microvascular resistance (IMR) response to multiple hyperaemic agents in the human coronary circulation. METHODS: Thermodilution-derived IMR was determined during intravenous adenosine, intracoronary acetylcholine, and intravenous dobutamine in patients with ischemic symptoms and nonobstructive coronary angiograms. A total of 128 patients were studied (44 with adenosine and acetylcholine, and 84 with all agents). Adenosine IMR >25, acetylcholine IMR >31, and dobutamine IMR >29 were used to define elevated responses. RESULTS: IMR responses demonstrated weak-to-moderate association (adenosine vs acetylcholine IMR: ρ = 0.33; adenosine vs dobutamine IMR: ρ = 0.51; acetylcholine vs dobutamine IMR: ρ = 0.28; all P < 0.01). Logistic regression analyses revealed that: (1) elevated adenosine IMR was associated with increasing age and left ventricle hypertrophy (odds ratio [OR] = 1.27 and 1.58; both P < 0.05, respectively), (2) elevated acetylcholine IMR was associated with increasing plasma uric acid (OR = 1.09; P < 0.05), and (3) elevated dobutamine IMR was associated with hypertension and left atrial volume index (OR = 3.99 and 1.07; both P < 0.05, respectively). Subset analyses to evaluate clinical utility of the acetylcholine and dobutamine IMR, independent of abnormal adenosine IMR, revealed that elevated acetylcholine and/or dobutamine IMR were associated with higher risk exercise stress tests, left atrial volumes, and burden of exertional chest pain. CONCLUSIONS: Microvascular-specific IMR responses to different hyperaemic agents are only moderately associated, whereas the predictors for agent-specific IMR responses varied, suggesting that multiple pharmacologic agents interrogate different microvascular control mechanisms.

CONTEXTE: On ne sait pas vraiment si les réponses microvasculaires coronariennes à de multiples agents hyperémiques aux modes d'action distincts ont des effets vasodilatateurs similaires ou partagent des facteurs prédictifs cliniques communs. Cette étude visait donc à caractériser la réponse selon l'indice de résistance microvasculaire (IMR) aux multiples agents hyperémiques dans la circulation coronarienne chez l'humain. MÉHODOLOGIE: L'IMR obtenu par thermodilution a été déterminé pendant l'administration intraveineuse d'adénosine, intracoronarienne d'acétylcholine et intraveineuse de dobutamine chez des patients présentant des symptômes ischémiques et par angiogrammes coronariens non obstructifs. Un total de 128 patients (44 avec l'adénosine et l'acétylcholine, et 84 avec tous les agents) ont fait partie de l'étude. Des réponses élevées étaient définies par un IMR à l'adénosine > 25, un IMR à l'acétylcholine > 31 et un IMR à la dobutamine > 29. RÉSULTATS: Les réponses selon l'IMR ont révélé une association faible à modérée (IMR à l'adénosine vs IMR à l'acétylcholine : ρ = 0,33; IMR à l'adénosine vs IMR à la dobutamine : ρ = 0,51; IMR à l'acétylcholine vs IMR à la dobutamine : ρ = 0,28; tous : p < 0,01). Des analyses de régression logistique ont révélé que : 1) un IMR à l'adénosine élevé était associé à l'avancement en âge et à une hypertrophie ventriculaire gauche (rapport des cotes [RC] = 1,27 et 1,58; p < 0,05 respectivement pour les deux), 2) un IMR à l'acétylcholine élevé était associé à l'augmentation de la concentration plasmatique d'acide urique (RC = 1,09; p < 0,05) et 3) un IMR à la dobutamine élevé était associé à l'hypertension et à l'indice de volume auriculaire gauche (RC = 3,99 et 1,07; p < 0,05 respectivement pour les deux). Des analyses par sous-groupes visant à évaluer l'utilité clinique de l'IMR à l'acétylcholine et à la dobutamine, indépendamment d'un IMR à l'adénosine anormal, ont révélé que des IMR à l'acétylcholine et/ou à la dobutamine élevés étaient associés à une augmentation du risque lors des épreuves à l'effort, à un volume auriculaire gauche plus élevé et à une augmentation du fardeau associé à la douleur thoracique à l'effort. CONCLUSIONS: Les réponses microvasculaires selon l'IMR à différents agents hyperémiques sont seulement modérément associées, alors que les facteurs prédictifs des réponses selon l'IMR spécifique de l'agent varient, ce qui laisse croire que les multiples agents pharmacologiques font appel à différents mécanismes de contrôle microvasculaire.

Noninvasive Microvascular Indices Reveal Peripheral Vascular Abnormalities in Patients With Suspected Coronary Microvascular Dysfunction.

BACKGROUND: Reactive hyperemia peripheral arterial tonometry and flow-mediated dilation are common noninvasive measures of peripheral vascular function. However, their relationship with the coronary circulation, particularly in coronary microvascular dysfunction (CMD), is unclear. Therefore, the purpose of this study is to compare these noninvasive measurements with coronary microvascular function after endothelial-independent, endothelial-dependent, and sympathetically mediated pharmacologic hyperemia. METHODS: Forty-seven patients with suspected CMD completed peripheral and coronary assessments. The reactive hyperemia index was collected using the EndoPAT2000 device, whereas a subset of patients (n = 28) completed brachial artery flow-mediated dilation using duplex ultrasound. Coronary microvascular function was quantified using the resistance and flow responses to intravenous adenosine (140 µg/kg/min), dobutamine (40 µg/kg/min), and intracoronary acetylcholine (100 µg). Abnormal coronary microvascular responses to adenosine and/or acetylcholine were used to define CMD. RESULTS: The reactive hyperemia index (No CMD: 0.85 ± 0.23 vs CMD: 0.61 ± 0.26, P < 0.05) and flow-mediated dilation (No CMD: 7.2 ± 2.3 vs CMD: 4.8 ± 3.1; P < 0.05) were attenuated in patients with CMD. Whereas the reactive hyperemia index was correlated with the resistance and flow responses to dobutamine (ρ = -0.44 and ρ = 0.39, respectively; P < 0.05), flow-mediated dilation was correlated with the resistance responses to both adenosine (ρ = -0.48; P < 0.05) and acetylcholine (ρ = -0.66; P < 0.05). Lastly, the reactive hyperemia index and flow-mediated dilation had sensitivities of 80% and 69% and specificities of 71% and 93%, respectively, for identifying patients with CMD. CONCLUSIONS: Peripheral vascular function is attenuated in CMD, and noninvasive measurements are associated with coronary responses to pharmaceutical stimulation.

Changes in the prevalence of chronic conditions associated with abdominal obesity between 1999 and 2014.

To examine the trends in chronic conditions after accounting for temporal differences in body mass index (BMI) and waist circumference (WC). Pooled cycles (1999-2014) of the U.S. National Health and Nutrition Examination Survey (NHANES) were analysed (n = 36 959). The models were adjusted for caloric intake, smoking, medications use and physical activity. The prevalence of diabetes increased in women with general or abdominal obesity (BMI*time; WC*time, P < .05), but there were no differences in men. For hypertension, independent of BMI, the prevalence was not different over time in both sexes (P > .05), whereas for a given WC, there was a decrease in the prevalence over time in women (WC*time, P = .05). For dyslipidemia, independent of BMI, the prevalence decreased in men, whereas for a given WC, there was a decrease in the prevalence in both sexes (P < .05). Over the same time frame, blood pressure, low-density lipoprotein and triglycerides decreased, while plasma glucose increased independent of general and abdominal obesity (P < .001). The relationship between obesity and chronic conditions has changed over time. There may be other changes that have altered how obesity is related with metabolic health markers over time. Further investigation is needed to better understand the current causes of chronic conditions.

Metabolically healthy obesity, vitamin D, and all-cause and cardiometabolic mortality risk in NHANES III.

BACKGROUND & AIMS: Previous studies assessing the prognosis of metabolically healthy obesity (MHO) have been limited by a lack of a harmonized definition of MHO phenotype. Furthermore, obesity is a risk factor for vitamin D deficiency and low vitamin D status has been associated with a higher risk of mortality; however, few studies have evaluated the joint association between vitamin D, metabolic health phenotype, and mortality risk. Using a harmonized definition, we investigated whether MHO is associated with subsequent all-cause and cardiometabolic mortality, and whether serum 25-hydroxyvitamin D [25(OH)D] modifies these associations. METHODS: This study included participants aged ≥20 years from the Third National Health and Nutrition Examination Survey (NHANES III). MHO phenotype was defined as a combination of obesity (≥30 kg/m2) and zero component of metabolic syndrome. Multivariable Cox regression was used to assess the risk of mortality across metabolic phenotypes, and the joint association between metabolic phenotype and 25(OH)D. Fine and Gray regression was performed to account for competing risk events. RESULTS: Among 11,333 participants, a total of 2980 deaths (937 cardiometabolic death outcomes) occurred during a median follow-up of 19.1 years. In the absence of any metabolic abnormality, obesity (MHO) was not associated with a higher risk of all-cause (hazard ratio [HR], 0.89 [95% CI, 0.52-1.51]) or cardiometabolic mortality (cause-specific HR, 1.21 [95% CI 0.33-4.46]). Similar results were obtained from competing risk analysis. No significant differences in average 25(OH)D levels were observed between MHO and non-MHO participants; however, there was a significant interaction between metabolic health phenotype and serum 25(OH)D in relation to cardiometabolic mortality such that levels of serum 25(OH)D < 50 nmol/L were associated with increased risk of cardiometabolic mortality, particularly in participants within the normal-weight and obese BMI ranges. CONCLUSIONS: Our results support the hypothesis that MHO phenotype is a benign health condition. Vitamin D deficiency may exacerbate the risk of cardiometabolic death outcomes associated with metabolic dysfunction in normal weight and obese individuals. Further research is warranted to validate our findings.

Changes in adiposity and other factors in relation to age at natural menopause: analyses from the coronary artery risk development (CARDIA) study.

OBJECTIVE: The age at natural menopause has subsequent health implications. Earlier age at natural menopause is a risk factor for cardiovascular disease, atherosclerosis, and stroke. Despite extensive study, no clear and conclusive association between anthropometric measures and age at natural menopause has emerged. This study aims to assess whether baseline and/or longitudinal changes in adiposity are associated with age at natural menopause. METHODS: In all, 2,030 premenopausal women from the Coronary Artery Risk Development in Young Adults study-a prospective study with 25 years follow-up-were included for analysis from 1985 to 1986 until menopause was attained. Anthropometry included body mass index and waist circumference. Discrete-time survival analysis was then used to determine the association between anthropometric measures at baseline, and also their changes with age at natural menopause, while adjusting for various time-varying and invariant covariates in separate models for body mass index and waist circumference. RESULTS: Multivariate Cox regression analysis showed that baseline body mass index (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.94-0.98) and baseline waist circumference (HR 0.98, 95% CI 0.97-0.99) significantly increased the risk of later age at natural menopause. Neither time-varying body mass index nor waist circumference indicating change across time associated with age at natural menopause. Premenopausal hypertension was strongly associated with an earlier age at natural menopause. CONCLUSION: These findings show that age at natural menopause is partly determined by modifiable factors such as premenopausal hypertension and baseline adiposity. These results highlight the importance of both control and prevention of cardiovascular risk factors such as excess weight in early to mid-adulthood before menopause onset.

Lifetime risk of cardiometabolic mortality according to vitamin D status of middle and older-aged adults: NHANES III mortality follow-up.

The predictive value of total 25-hydroxyvitamin D (25(OH)D, a biomarker of vitamin D status) in relation to lifetime risk of cardiometabolic mortality is not known. The purpose of this study was to determine the association between standardized and annualized total 25(OH)D levels and lifetime risk for cardiometabolic mortality in middle- to older-aged adults. In this study, we followed up 7958 participants in the Third National Health and Nutrition Examination Survey from 1988 to 1994 (NHANES III) until the occurrence of cardiometabolic death or attainment of 95 years of age (median follow-up 17.9 years, 1371 cardiometabolic-deaths). Lifetime risks were estimated according to recommended total 25(OH)D cutoffs by national guidelines, and a combination of total 25(OH)D status and traditional risk factor burden. We also explored variation in lifetime risk estimates by levels of body mass index (BMI). The results of this study showed that annualized total 25(OH)D <30 nmol/L was associated with high lifetime risk of cardiometabolic mortality (40%). Lifetime risks of cardiometabolic mortality were similar for annualized levels between 30-< 50 nmol/L, 50-< 75 nmol/L and ≥75 nmol/L (31-33%). Lifetime risk was highest among participants with annualized total 25(OH)D <30 nmol/L and ≥2 major traditional risk factors (45%), whereas lifetime risk was lowest among participants with annualized 25(OH)D ≥30 nmol/L and low-intermediate risk factors (28%). Lifetime risk estimates were similar across BMI categories. In conclusion, a single measurement of vitamin D deficiency (annualized levels <30 nmol/L) in middle- to older-aged adults is a strong predictor of high lifetime risk for cardiometabolic mortality, particularly among those with high burden of traditional risk factors.

The Association Between Metabolic Syndrome and Serum Concentrations of Micronutrients, Inflammation, and Oxidative Stress Outside of the Clinical Reference Ranges: A Cross-Sectional Study.

BACKGROUND: Clinical reference ranges are often used to assess nutritional status, but whether having lower or higher than the current clinical reference range for micronutrients, inflammation, and oxidative stress is related to metabolic syndrome (MetS) is not known. Our objectives are to estimate the odds of having MetS outside of established clinical references, and to identify any effect modifications by sex have for these relationships. METHODS: Data from the 2005 to 2006 National Health and Nutrition Examination Survey were used (≥20 years; N = 2049) with MetS defined utilizing the harmonized criteria from the Joint Interim Statement. The odds of having MetS in individuals with lower or higher than the clinical reference range for the serum concentrations of micronutrient antioxidants, inflammation, and oxidative stress were estimated following adjustments for age, sex, ethnicity, education, income, smoking, alcohol intake, recreational physical activity, and BMI. RESULTS: Having lower than the clinical reference range for carotenoids and vitamin C [odds ratios (95% confidence interval): 1.37 (1.05-1.78) and 1.39 (1.01-1.90), respectively] was associated with significantly greater odds of MetS. By contrast, having higher than the clinical reference range for vitamins A and E, uric acid, and γ-glutamyl transferase (GGT) [2.10 (1.50-2.92), 2.36 (1.78-3.13), 2.65 (1.54-4.57), and 2.08 (1.61-2.69), respectively] was associated with higher odds of MetS, whereas higher levels of vitamins B12 were protective [0.64 (0.42-0.98]. Sex moderated these relationships for carotenoids, vitamin A, C, E, uric acid, C-reactive protein, and GGT. CONCLUSIONS: Lower carotenoids and vitamin C and higher vitamins A and E, uric acid, and oxidative stress were associated with a greater likelihood of MetS, whereas higher vitamin B12 was protective. Further research is necessary to replicate these findings in a prospective setting to confirm the importance of the overall and sex-specific findings.