Monosodium urate (MSU) crystals increase gout associated coronary heart disease (CHD) risk through the activation of NLRP3 inflammasome

Gout is a recurrent and chronic form of arthritis caused by the deposition of monosodium urate (MSU) crystals in the joints. Macrophages intake MSU crystals, the trigger for NLRP3 inflammasome activation, which leads to the release of interleukin (IL)-1β and results in the flaring of gout. The effects of temperature, an environmental factor for MSU crystallization, on IL-1β secretion have not been well studied. This study examined the effects of temperature on inflammasome activation. Specific triggers activated canonical inflammasomes (NLRP3, NLRC4, and AIM2) in murine macrophages at various temperatures (25, 33, 37, 39, and 42 °C). The maturation of IL-1β and caspase-1 was measured as an indicator for inflammasome activation. As expected, the optimal temperature of inflammasome activation was 37 °C. The MSU crystal-mediated activation of inflammasome increased at temperatures lower than 37 °C and decreased at higher temperatures. MSU crystals at lower temperatures enhanced IL-1β secretion via the NLRP3 inflammasome pathway. A lower temperature promoted the formation of MSU crystals without changing phagocytosis. Overall, lower temperatures form more MSU crystals and enhance NLRP3 inflammasome activation. In light of these findings, it is possible that hyperthermia therapy may reduce gout flaring.

Download Full-text

Risk of coronary heart disease among cancer survivors with different prediagnosis body mass index

Scientific Reports ◽

10.1038/s41598-021-82026-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ahryoung Ko ◽

Kyuwoong Kim ◽

Joung Sik Son ◽

Yu Jin Cho ◽

Sang Min Park ◽

...

Keyword(s):

Body Mass Index ◽

Coronary Heart Disease ◽

Heart Disease ◽

Cancer Survivors ◽

Body Mass ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer Site ◽

Chd Risk

AbstractAssociation between body mass index (BMI) and coronary heart disease (CHD) in cancer survivors is not clearly established. This study analyzed the prediagnosis BMI-CHD association by examining 13,500 cancer survivors identified from the National Health Insurance Service-Health Screening Cohort from January 1, 2004 to December 31, 2009 including the patients who were free of cardiovascular disease at enrollment. The Cox proportional hazards model (adjusted for socioeconomic, health behavior, health status, and medical characteristics) was used for calculating hazard ratios (HR) and 95% confidence intervals (95% CI) for CHD in each prediagnosis BMI category among cancer survivors. Compared to cancer survivors with a prediagnosis BMI between 18.5 and 22.9 kg/m2, those with a prediagnosis BMI of 23.0–24.9 kg/m2 and ≥ 25.0 kg/m2 had significantly higher CHD risk (HR = 1.51; 95% CI: 1.13–2.01 and HR = 1.38; 95% CI: 1.04–1.84, respectively). Cancer survivors with a low prediagnosis BMI (< 18.5 kg/m2) also had significantly higher CHD risk (HR = 1.97; 95% CI: 1.20–3.24) compared to those with a BMI of 18.5–22.9 kg/m2. Similar associations were found after stratifying analyses based on first cancer site and sociodemographic and medical characteristic subgroups. Our study suggests that prediagnosis underweight among patients with cancer is a predictor of CHD risk.

Download Full-text

Saturated Fat Consumption and Risk of Coronary Heart Disease and Ischemic Stroke: A Science Update

Annals of Nutrition and Metabolism ◽

10.1159/000455681 ◽

2017 ◽

Vol 70 (1) ◽

pp. 26-33 ◽

Cited By ~ 42

Author(s):

Joyce A. Nettleton ◽

Ingeborg A. Brouwer ◽

Johanna M. Geleijnse ◽

Gerard Hornstra

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Ischemic Stroke ◽

Saturated Fat ◽

The Body ◽

Epidemiological Methods ◽

Risk Markers ◽

Fat Consumption ◽

Chd Risk ◽

Important Health

At a workshop to update the science linking saturated fatty acid (SAFA) consumption with the risk of coronary heart disease (CHD) and ischemic stroke, invited participants presented data on the consumption and bioavailability of SAFA and their functions in the body and food technology. Epidemiological methods and outcomes were related to the association between SAFA consumption and disease events and mortality. Participants reviewed the effects of SAFA on CHD, causal risk factors, and surrogate risk markers. Higher intakes of SAFA were not associated with higher risks of CHD or stroke apparently, but studies did not take macronutrient replacement into account. Replacing SAFA by cis-polyunsaturated fatty acids was associated with significant CHD risk reduction, which was confirmed by randomized controlled trials. SAFA reduction had little direct effect on stroke risk. Cohort studies suggest that the food matrix and source of SAFA have important health effects.

Download Full-text

The Impact of Risk Factors for Coronary Heart Disease on Related Disability in Older Irish Adults

Journal of Aging and Health ◽

10.1177/0898264317726242 ◽

2017 ◽

Vol 31 (1) ◽

pp. 165-184 ◽

Cited By ~ 1

Author(s):

Sharon M. Cruise ◽

John Hughes ◽

Kathleen Bennett ◽

Anne Kouvonen ◽

Frank Kee

Keyword(s):

Risk Factors ◽

Coronary Heart Disease ◽

Heart Disease ◽

Northern Ireland ◽

Physical Inactivity ◽

Relative Risks ◽

Chd Risk ◽

Health And Social Care ◽

Chd Risk Factors ◽

The Impact

Objective: The aim of this study is to examine the prevalence of coronary heart disease (CHD)–related disability (hereafter also “disability”) and the impact of CHD risk factors on disability in older adults in the Republic of Ireland (ROI) and Northern Ireland (NI). Method: Population attributable fractions were calculated using risk factor relative risks and disability prevalence derived from The Irish Longitudinal Study on Ageing and the Northern Ireland Health Survey. Results: Disability was significantly lower in ROI (4.1% vs. 8.8%). Smoking and diabetes prevalence rates, and the fraction of disability that could be attributed to smoking (ROI: 6.6%; NI: 6.1%), obesity (ROI: 13.8%; NI: 11.3%), and diabetes (ROI: 6.2%; NI: 7.2%), were comparable in both countries. Physical inactivity (31.3% vs. 54.8%) and depression (10.2% vs. 17.6%) were lower in ROI. Disability attributable to depression (ROI: 16.3%; NI: 25.2%) and physical inactivity (ROI: 27.5%; NI: 39.9%) was lower in ROI. Discussion: Country-specific similarities and differences in the prevalence of disability and associated risk factors will inform public health and social care policy in both countries.

Download Full-text

Risk Factors for Coronary Artery Disease in Children: Recognition, Evaluation, and Therapy

Pediatrics in Review ◽

10.1542/pir.2.5.131 ◽

1980 ◽

Vol 2 (5) ◽

pp. 131-138

Author(s):

C. J. Glueck ◽

M. J. Mellies ◽

R. C. Tsang ◽

J. A. Morrison

Keyword(s):

Risk Factors ◽

Coronary Heart Disease ◽

Heart Disease ◽

Eating Habits ◽

Plasma Cholesterol ◽

Saturated Fat ◽

Cholesterol Levels ◽

Chd Risk ◽

Artery Disease ◽

Atherosclerosis Prevention

PEDIATRIC GENESIS OF ATHEROSCLEROSIS Atherosclerosis results from a variety of pathophysiologic disturbances, some currently recognized, and many undoubtedly not yet recognized, which in aggregate are identified as risk factors. Genetic and environmental influences conjointly affect the incidence and the severity of these risk factors and, thus, coronary heart disease (CHD) risk. Prophylaxis should be designed to prevent or retard the development of arterial plaques. This suggests that diagnostic and preventive efforts should begin in childhood. Eating habits are also probably established in childhood, allowing their early modification. The atherosclerotic plaque appears to have its genesis in childhood. The data from wartime autopsies confirm the presence of mature atherosclerotic lesions by the end of the second decade and emphasize the importance of primary atherosclerosis prevention beginning in the first and second decades. While there are clearly genetic factors in CHD, variation in rates in differing geographic areas appears less likely to be related to genetic than to environmental differences. Marked differences in plasma cholesterol levels are found in children in different geographic areas, generally paralleling pediatric cholesterol and saturated fat intake and the incidence of adult coronary heart disease. The relationships of elevated total plasma cholesterol levels to the incidence of coronary heart disease are clearly established in adults.

Download Full-text

Abstract P316: Prehypertension and Incident Acute Coronary Heart Disease in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽

10.1161/circ.127.suppl_12.ap316 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Stephen P Glasser ◽

Yulia Khodneva ◽

Daniel Lackland ◽

Ronald Prineas ◽

Monika Safford

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Racial Differences ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Cox Proportional Hazards Models ◽

Chd Risk ◽

Regards Study ◽

Chd Risk Factors

Objective: The independent prognostic value of prehypertension (preHTN) for incident coronary heart disease (CHD) remains unsettled. Using the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study, we examined associations between preHTN and incident acute CHD and CVD death. Methods: REGARDS includes 30,239 black and white community-dwelling adults age 45 and older at baseline. Recruitment occurred from 2003-7, with baseline interviews and in-home data collection for physiologic measures. Follow-up is conducted by telephone every 6 months to detect events and deaths, which are adjudicated by experts. Systolic BP was categorized into <120 mmHg (n=4385), 120-129 mmHg (n=4000), 130-139 (n=2066), and hypertension was categorized into controlled (<140/90 mmHg on treatment) (n=8378), and uncontrolled (>140/90 mmHg) (n=5364). Incident acute CHD was defined as definite or probable myocardial infarction (MI) or acute CHD death. CVD death was defined as acute CHD, stroke, heart failure or other cardiovascular disease related. Cox proportional hazards models estimated the hazard ratios (HR) for incident CHD by BP categories, adjusting for sociodemographics and CHD risk factors. Results: The 23,393 participants free of CHD at baseline were followed for a median of 4.4 years. Mean age was 64.1, 58% were women and 42% were black. There was a significant interaction between sex and BP categories, therefore analyses were stratified by sex. There were 252 non-fatal and fatal acute CHD events among women and 407 among men. Among women, compared with SBP<120 mmHg, BP categories above SBP 120 mmHg were associated with incident CHD (adjusted HR for SBP120-129 mmHg=1.94 {95% CI 1.04-3.62]; SBP 130-139 mmHg=1.92 {0.95-3.87}; controlled HTN=2.16 {1.25-3.75}; uncontrolled HTN=3.25 {1.87-5.65}) in fully adjusted models. Among men, only uncontrolled HTN was associated with incident CHD (HR=1.55 {1.11-2.17}). Conclusion: In this sample, preHTN may be associated with incident CHD among women but not men.

Download Full-text

Abstract P192: Metabolomic Profiles Associated with Coronary Heart Disease in Women

Circulation ◽

10.1161/circ.133.suppl_1.p192 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Nina P Paynter ◽

Raji Balasubramanian ◽

Shuba Gopal ◽

Franco Giulianini ◽

Leslie Tinker ◽

...

Keyword(s):

Risk Factors ◽

Coronary Heart Disease ◽

Logistic Regression ◽

Heart Disease ◽

Tier 2 ◽

Validation Data ◽

Data Set ◽

Chd Risk ◽

Tier 1 ◽

Chd Risk Factors

Background: Prior studies of metabolomic profiles and coronary heart disease (CHD) have been limited by relatively small case numbers and scant data in women. Methods: The discovery set examined 371 metabolites in 400 confirmed, incident CHD cases and 400 controls (frequency matched on age, race/ethnicity, hysterectomy status and time of enrollment) in the Women’s Health Initiative Observational Study (WHI-OS). All selected metabolites were validated in a separate set of 394 cases and 397 matched controls drawn from the placebo arms of the WHI Hormone Therapy trials and the WHI-OS. Discovery used 4 methods: false-discovery rate (FDR) adjusted logistic regression for individual metabolites, permutation corrected least absolute shrinkage and selection operator (LASSO) algorithms, sparse partial least squares discriminant analysis (PLS-DA) algorithms, and random forest algorithms. Each method was performed with matching factors only and with matching plus both medication use (aspirin, statins, anti-diabetics and anti-hypertensives) and traditional CHD risk factors (smoking, systolic blood pressure, diabetes, total and HDL cholesterol). Replication in the validation set was defined as a logistic regression coefficient of p<0.05 for the metabolites selected by 3 or 4 methods (tier 1), or a FDR adjusted p<0.05 for metabolites selected by only 1 or 2 methods (tier 2). Results: Sixty-seven metabolites were selected in the discovery data set (30 tier 1 and 37 tier 2). Twenty-six successfully replicated in the validation data set (21 tier 1 and 5 tier 2), with 25 significant with adjusting for matching factors only and 11 significant after additionally adjusting for medications and CHD risk factors. Validated metabolites included amino acids, sugars, nucleosides, eicosanoids, plasmologens, polyunsaturated phospholipids and highly saturated triglycerides. These include novel metabolites as well as metabolites such as glutamate/glutamine, which have been shown in other populations. Conclusions: Multiple metabolites in important physiological pathways with robust associations for risk of CHD in women were identified and replicated. These results may offer insights into biological mechanisms of CHD as well as identify potential markers of risk.

Download Full-text

Abstract 13168: Food Quality Score and the Risk of Coronary Heart Disease

Circulation ◽

10.1161/circ.132.suppl_3.13168 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Teresa Fung ◽

An Pan ◽

Tao Hou ◽

Dariush Mozzafarian ◽

Shilpa Bhupathiraju ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Food Quality ◽

Diet Quality ◽

Healthy Eating Index ◽

Quality Score ◽

Health Study ◽

Standard Deviation Increase ◽

Chd Risk ◽

History Of

Introduction: We have previously derived a food based diet quality score associated with weight change. In this analysis, we prospectively assessed the association between this score and risk of coronary heart disease (CHD). Methods: We followed 74,667 women in the Nurse’ Health Study (baseline age 35-55 y), 28,977 men in the Health Professionals Follow-up Study (baseline age 50-72), and 92,513 women in the Nurses’ Health Study 2 (baseline age 25-42) without a history of cardiovascular disease for up to 26 years between 1984 and 2011. Diet was assessed up to 7 times using repeated food frequency questionnaires. We computed the Food Quality Score (FQS) for each individual. A higher FQS score represents a healthier diet. The association between the FQS and CHD risk was assessed using Cox proportional hazard model controlling for potential confounders. We also compared the strength of association of FQS with other diet quality scores. Results: We ascertained 6497 incident CHD events, including 4594 nonfatal myocardial infarct (MI) and 2055 fatal cases. Comparing top to bottom deciles, the pooled RR was 0.66 (95% CI=0.58-0.74, p trend<0.001) for total CHD, 0.63 (0.54-0.73, p trend<0.001) for non-fatal MI, and 0.73 (0.59-0.90, p trend=0.001) for fatal MI. The association for CHD was significant in lean (BMI<25) and overweight (BMI>=25) individuals, those with or without a family history of MI, and physical activity above or below the median. When comparing the FQS with other diet quality scores that have previously been associated to lower CHD risk, one standard deviation increase in the FQS was not significantly different from the Alternate Mediterranean Diet score, the Alternate Healthy Eating Index-2010 or the Dietary Approaches to Stop Hypertension score in its association with CHD risk. Conclusion: A higher FQS was associated with lower CHD risk. The FQS was comparable to food and nutrient based diet quality score that have previously been associated with lower CVD risk and indicates a potential to develop a simple food only diet quality for public health applications of assessing diet quality.

Download Full-text

Abstract P001: Dietary and Plasma Magnesium and Risk of Coronary Heart Disease among Women

Circulation ◽

10.1161/circ.125.suppl_10.ap001 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Stephanie E Chiuve ◽

Kathryn M Rexrode ◽

Qi Sun ◽

Eric N Taylor ◽

Gary C Curhan ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Lower Risk ◽

Threshold Effect ◽

Health Study ◽

Control Analysis ◽

Inverse Association ◽

Chd Risk ◽

Plasma Magnesium ◽

Chd Risk Factors

Background: Plasma magnesium (Mg) has been strongly associated with lower risk of fatal coronary heart disease (CHD) and sudden cardiac death, which may be due to its anti-arrhythmic properties. Mg also affects endothelial function, inflammation, blood pressure and diabetes and thus may impact atherosclerosis in general. We examined the association between magnesium, measured in diet and plasma, and risk of fatal, nonfatal and total CHD among women in the Nurses’ Health Study. Design: The association for Mg intake was examined prospectively among 86,361 women free of disease in 1980. Mg intake and other covariates were ascertained updated every 2-4 years through questionnaires and 3661 cases of CHD (1214 fatal/2447 nonfatal) were documented through 2008. For plasma Mg, we conducted a nested case-control analysis with 405 CHD (63 fatal/342 nonfatal) cases, matched to controls (1:1) on age, smoking, fasting status, and date of blood sampling. Results: Dietary magnesium was inversely associated with risk of CHD, even after controlling for diet and CHD risk factors (RR comparing extreme quintiles: 0.75; 95%CI: 0.64, 0.89; P trend=0.002) (Table 1). The relationship with plasma Mg was less linear ( P trend=0.09) with a potential threshold effect at the 2 nd quintile. The RR of CHD comparing plasma Mg >2.0 v. ≤2.0 mg/dl was 0.49 (95%CI: 0.32, 0.74). The associations for dietary and plasma Mg appeared stronger for fatal versus nonfatal CHD. The RR (95%CI; P trend) comparing the highest to lowest quintile of dietary Mg was 0.60 (0.45, 0.79; p <0.001) for fatal and 0.85 (0.70, 1.04; p = 0.14) for nonfatal CHD. The RR (95%CI) comparing plasma Mg >2.0 v. ≤2.0 mg/dl was 0.23 (0.07, 0.81) for fatal and 0.55 (0.35, 0.86) for nonfatal CHD. Conclusions: Higher levels of Mg, in diet and plasma, were associated with lower risk of total CHD among women. The consistent inverse association found between two measures of Mg and CHD risk supports the hypothesis that Mg might lower CHD risk through multiple mechanisms, and may be most strongly protective for fatal events.

Download Full-text