scholarly journals Remnant Cholesterol and Myocardial Infarction in Normal Weight, Overweight, and Obese Individuals from the Copenhagen General Population Study

2018 ◽  
Vol 64 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Anette Varbo ◽  
Jacob J Freiberg ◽  
Børge G Nordestgaard
Keyword(s):  
Myocardial Infarction ◽  
Body Mass Index ◽  
Risk Factor ◽  
General Population ◽  
Population Study ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
General Population Study ◽  
Hazard Ratios ◽  
Remnant Cholesterol

Abstract BACKGROUND We tested whether high remnant cholesterol is associated with high myocardial infarction risk, independent of whether an individual is normal weight, overweight, or obese. METHODS A total of 106216 individuals from the Copenhagen General Population Study were followed for up to 11 years, during which 1565 experienced a myocardial infarction. Individuals were grouped by clinically meaningful remnant cholesterol concentrations of <0.5 mmol/L (19 mg/dL), 0.5 to 0.99 mmol/L (19–38 mg/dL), 1.0 to 1.49 mmol/L (39–58 mg/dL), and ≥1.5 mmol/L (58 mg/dL), and by body mass index (BMI) of <18.5 kg/m2 (underweight), 18.5 to 24.9 kg/m2 (normal weight), 25 to 29.9 kg/m2 (overweight), and ≥30 kg/m2 (obese). RESULTS Median calculated remnant cholesterol was 0.40 mmol/L [interquartile range (IQR), 0.30–0.55 mmol/L] [15 mg/dL (12–21 mg/dL)] for underweight, 0.50 mmol/L (IQR, 0.37–0.71 mmol/L) [19 mg/dL (14–27 mg/dL)] for normal weight, 0.70 mmol/L (IQR, 0.49–1.00 mmol/L) [27 mg/dL (19–39 mg/dL)] for overweight, and 0.85 mmol/L (IQR, 0.61–1.20 mmol/L) [(33 mg/dL (24–46 mg/dL)] for obese individuals. On continuous scales, remnant cholesterol was positively correlated with BMI until reaching a plateau of approximately 1 mmol/L (39 mg/dL) at BMI >35 kg/m2. R2 from an unadjusted linear regression for the correlation between calculated remnant cholesterol and BMI was 12%. Stepwise higher remnant cholesterol was associated with stepwise higher myocardial infarction risk in a similar pattern for normal weight, overweight, and obese individuals. When compared with individuals with remnant cholesterol <0.5 mmol/L (19 mg/dL), individuals with remnant cholesterol ≥1.5 mmol/L (58 mg/dL) had hazard ratios for myocardial infarction of 2.0 (95% CI, 1.3–3.2) for normal weight, 1.9 (95% CI, 1.4–2.6) for overweight, and 2.3 (95% CI, 1.4–3.5) for obese individuals. Directly measured remnant cholesterol increased 0.91 mmol/L (95% CI, 0.89–0.94 mmol/L) [35 mg/dL (34–36 mg/dL)] per 1 mmol/L (39 mg/dL) increase in calculated remnant cholesterol. CONCLUSIONS Remnant cholesterol and BMI were positively correlated; however, high remnant cholesterol was associated with higher myocardial infarction risk across the examined BMI subcategories, indicating that remnant cholesterol is a risk factor for myocardial infarction independent of overweight and obesity.

Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study

2016 ◽  
Vol 34 (11) ◽  
pp. 1208-1216 ◽  
Author(s):  
Charlotte Näslund-Koch ◽  
Børge G. Nordestgaard ◽  
Stig E. Bojesen
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Population Study ◽  
Cell Cycle Checkpoint ◽  
Loss Of Function ◽  
General Population Study ◽  
Chek2 1100Delc ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Age And Sex

Purpose CHEK2 is a cell cycle checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increased breast cancer risk. It seems plausible that this mutation could also predispose to other cancers. Therefore, we tested the hypothesis that CHEK2*1100delC heterozygosity is associated with increased risk for other cancers in addition to breast cancer in the general population. Patients and Methods We examined 86,975 individuals from the Copenhagen General Population Study, recruited from 2003 through 2010. The participants completed a questionnaire on health and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were calculated using Kaplan-Meier estimates, Fine and Gray competing-risks regressions, and stratified analyses with interaction tests. Results Among 86,975 individuals, 670 (0.8%) were CHEK2*1100delC heterozygous, 2,442 developed breast cancer, and 6,635 developed other cancers. The age- and sex-adjusted hazard ratio for CHEK2*1100delC heterozygotes compared with noncarriers was 2.08 (95% CI, 1.51 to 2.85) for breast cancer and 1.45 (95% CI, 1.15 to 1.82) for other cancers. When stratifying for sex, the age-adjusted hazard ratios for other cancers were 1.54 (95% CI, 1.08 to 2.18) for women and 1.37 (95% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer. Conclusion CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation.

Triglycerides and remnant cholesterol associated with risk of aortic valve stenosis: Mendelian randomization in the Copenhagen General Population Study

2020 ◽  
Vol 41 (24) ◽  
pp. 2288-2299 ◽  
Author(s):  
Morten Kaltoft ◽  
Anne Langsted ◽  
Børge G Nordestgaard
Keyword(s):  
Aortic Valve ◽  
General Population ◽  
Aortic Valve Stenosis ◽  
Population Study ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
General Population Study ◽  
Plasma Triglycerides ◽  
Increased Risk ◽  
Remnant Cholesterol

Abstract Aims We tested the hypothesis that higher levels of plasma triglycerides and remnant cholesterol are observationally and genetically associated with increased risk of aortic valve stenosis. Methods and results We included 108 559 individuals from the Copenhagen General Population Study. Plasma triglycerides, remnant cholesterol (total cholesterol minus low-density lipoprotein and high-density lipoprotein cholesterol), and 16 genetic variants causing such increased or decreased levels were determined. Incident aortic valve stenosis occurred in 1593 individuals. Observationally compared to individuals with triglycerides <1 mmol/L (<89 mg/dL), the multifactorially adjusted hazard ratio for aortic valve stenosis was 1.02 [95% confidence interval (CI) 0.87–1.19] for individuals with triglycerides of 1.0–1.9 mmol/L (89–176 mg/dL), 1.22 (1.02–1.46) for 2.0–2.9 mmol/L (177–265 mg/dL), 1.40 (1.11–1.77) for 3.0–3.9 mmol/L (266–353 mg/dL), 1.29 (0.88–1.90) for 4.0–4.9 mmol/L (354–442 mg/dL), and 1.52 (1.02–2.27) for individuals with triglycerides ≥5 mmol/L (≥443 mg/dL). By age 85, the cumulative incidence of aortic valve stenosis was 5.1% for individuals with plasma triglycerides <2.0 mmol/L (77 mg/dL), 6.5% at 2.0–4.9 mmol/L (177–442 mg/dL), and 8.2% for individuals with plasma triglycerides ≥5.0 mmol/L (443 mg/dL). The corresponding values for remnant cholesterol categories were 4.8% for <0.5 mmol/L (19 mg/dL), 5.6% for 0.5–1.4 mmol/L (19–57 mg/dL), and 7.4% for ≥1.5 mmol/L (58 mg/dL). Genetically, compared to individuals with allele score 13–16, odds ratios for aortic valve stenosis were 1.30 (95% CI 1.20–1.42; Δtriglycerides +12%; Δremnant cholesterol +11%) for allele score 17–18, 1.41 (1.31–1.52; +25%; +22%) for allele score 19–20, and 1.51 (1.22–1.86; +51%; +44%) for individuals with allele score 21–23. Conclusion Higher triglycerides and remnant cholesterol were observationally and genetically associated with increased risk of aortic valve stenosis.

scholarly journals BODY MASS INDEX AND COGNITIVE FUNCTION DECLINE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S815-S815
Author(s):  
Yingxiao Hua ◽  
Yingxiao Hua ◽  
Dexia Kong ◽  
XinQi Dong
Keyword(s):  
Older Adults ◽  
Body Mass Index ◽  
Risk Factor ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Body Mass ◽  
Work Memory ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Chinese Older Adults

Abstract Body composition has been proposed as an important modifiable risk factor of cognitive decline in multiple epidemiological studies. However, the relationship between body mass index (BMI) and cognitive function remains controversial and conflicting in diverse populations. This study aims to investigate the association between BMI and cognitive decline in U.S. Chinese older adults. Classifications of BMI are based on Asian criteria recommended by WHO (underweight: BMI<18.5, normal weight: 18.5≤BMI<23, overweight: 23≤bmi<27.5, obesity: bmi≥27.5). Logistic regression models were conducted. Compared with normal-weight participants, underweight participants were more likely to experience decline in episodic memory (OR=1.68, p=0.002) and work memory (OR=1.38, p=0.05). Being overweight and obesity were not associated with cognitive function decline. The findings indicate that underweight could potentially be a risk factor of cognitive function decline among U.S. Chinese older adults. Perspective studies may further investigate the association between weight loss and cognitive decline for the development of prevention strategies.

scholarly journals Association of Urbanization and Lower Light Exposure With Increased Body Mass Index

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A4-A5
Author(s):  
Débora Barroggi Constantino ◽  
Nicoli Xavier ◽  
Till Roenneberg ◽  
Maria Hidalgo ◽  
Luísa Pilz
Keyword(s):  
Body Mass Index ◽  
Risk Factor ◽  
Body Mass ◽  
Light Exposure ◽  
Normal Weight ◽  
Urban Environments ◽  
Overweight And Obesity ◽  
Future Research ◽  
Cross Sectional ◽  
Significant Difference

Abstract Introduction: Light/dark cycles are the main synchronizing signal (zeitgeber) that entrain human’s internal clock to the 24h-days. Some aspects of urban environments, including irregular light exposure and weak zeitgebers, influence the circadian organization and thereby may have an impact on metabolism. Comparing communities at different levels of urbanization and with different histories of access to electricity might provide evidence to support associations previously found between disrupted patterns of light exposure and increased populational rates of overweight and obesity. The present study aimed to investigate whether living at a higher level of urbanization would be associated with higher body mass index (BMI). It was hypothesized that BMI is higher in urbanized communities, since their inhabitants have weaker zeitgebers, often associated with disrupted circadian rhythms. Methods: We conducted a cross-sectional study in Quilombolas communities, located in the south of Brazil. Subjects were categorized into 5 groups based on their communities’ stage of urbanization and history of access to electricity: from rural with no access to electricity to highly urbanized communities that have access to the grid. We used data from 134 participants aged 16 - 92 years old (63% women), who had 7 days of light exposure recordings collected using wrist-worn actimeters. We also collected anthropometric data to calculate BMI, which was then categorized as follows: ≥18.5 kg/m² to <25 kg/m² = normal weight; ≥25 kg/m² to < 30 kg-m² = overweight; ≥ 30 kg/m² = obesity. We used Shapiro-Wilk to test for normality, Kruskal-Wallis followed by Dunn to compare BMI between groups and Spearman to assess whether there was an association between patterns of light exposure and BMI. Results: Kruskal-Wallis/Dunn test showed a significant difference in BMI between the urban group and the rural ones (KW: X² = 11.987, p < 0.001). Lower average light exposure between 7 am and 5 pm was significantly correlated with higher BMI (Spearman, r = - 0.296, p < 0.001). Also, higher average light exposure at night (from 1 am to 6 am) was significantly correlated with higher BMI (Spearman, r = 0.256, p = 0.002). Conclusions: Our results support the hypothesis that low amplitudes of light exposure may be a risk factor contributing to the high prevalence of obesity worldwide. Studies have previously shown associations between BMI and social jetlag, suggesting the correlations found in our study may be related to higher levels of circadian misalignment, more often present where zeitgeber strength is lower, as in urban environments. Future research is needed to address causal relationships between light exposure and excessive body mass in humans. Provided light exposure is a risk factor for obesity, these results point to potential new targets for intervention and prevention strategies.

Left ventricular trabeculation and major adverse cardiovascular events: the Copenhagen General Population Study

2020 ◽  
Vol 22 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Per E Sigvardsen ◽  
Andreas Fuchs ◽  
Jørgen T Kühl ◽  
Shoaib Afzal ◽  
Lars Køber ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
General Population ◽  
Population Study ◽  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
Left Ventricular ◽  
Major Adverse Cardiovascular Events ◽  
General Population Study

Abstract Aims  Prominent left ventricular trabeculations is a phenotypic trait observed in cardiovascular diseases. In the general population, the extent of left ventricular trabeculations is highly variable, yet it is unknown whether increased trabeculation is associated with adverse outcome. Methods and results  Left ventricular trabeculated mass (g/m2) was measured with contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. The primary endpoint was a composite of major adverse cardiovascular events and defined as death, heart failure, myocardial infarction, or stroke. The secondary endpoints were the individual components of the primary endpoint. Cox regression models were adjusted for clinical parameters, medical history, electrocardiographic parameters, and cardiac chamber sizes. The mean trabeculated mass was 19.1 g/m2 (standard deviation 4.9 g/m2). During a median follow-up of 4.0 years (interquartile range 1.5–6.7), 710 major adverse cardiovascular events occurred in 619 individuals. Individuals with a left ventricular trabeculated mass in the highest quartile had a hazard ratio for major adverse cardiovascular events of 1.64 [95% confidence interval (CI) 1.30–2.08; P < 0.001] compared to those in the lowest quartile. Corresponding hazard ratios were 2.08 (95% CI 1.38–3.14; P < 0.001) for death, 2.63 (95% CI 1.61–4.31; P < 0.001) for heart failure, 1.08 (95% CI 0.56–2.08; P = 0.82) for myocardial infarction, and 1.07 (95% CI 0.72–1.57; P = 0.74) for stroke. Conclusion  Increased left ventricular trabeculation is independently associated with an increased rate of major adverse cardiovascular events in the general population.

scholarly journals Plasma Ionized Calcium and Risk of Cardiovascular Disease: 106 774 Individuals from the Copenhagen General Population Study

2020 ◽  
Author(s):  
Camilla J Kobylecki ◽  
Børge G Nordestgaard ◽  
Shoaib Afzal
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Ischemic Stroke ◽  
General Population ◽  
Population Study ◽  
Reference Interval ◽  
High Plasma ◽  
Biologically Active ◽  
Ionized Calcium ◽  
General Population Study

Abstract Background Circulating total calcium or albumin-adjusted calcium is a risk factor for cardiovascular disease. As the biologically active ionized calcium is a physiologically more relevant measure and its association with cardiovascular disease is poorly understood, we tested the hypothesis that high plasma ionized calcium is associated with higher risk of myocardial infarction and ischemic stroke in individuals in the general population. Methods We included 106 774 individuals from the Copenhagen General Population Study, and defined hypocalcemia and hypercalcemia by the lowest and highest 2.5 percentiles, respectively, using the central 95% reference interval. Information on myocardial infarction and ischemic stroke was from registries and risks calculated using Cox regression and Fine and Gray competing-risks regression. Results During a median follow-up of 9.2 years, 4932 individuals received a diagnosis of either myocardial infarction or ischemic stroke. Hypercalcemia was associated with subdistribution hazard ratios of 1.67 (95%CI: 1.05–2.67) for myocardial infarction, 1.28 (0.81–2.02) for ischemic stroke, and of 1.54 (1.10–2.15) for the combined endpoint compared to individuals with plasma ionized calcium within the reference interval; hypocalcemia was not associated with cardiovascular disease. In models using plasma ionized calcium as a continuous variable, the associations were nonlinear; above the median, each 0.1 mmol/L higher plasma ionized calcium was associated with a hazard ratio of 1.31(1.02–1.68) for myocardial infarction, 1.21 (0.95–1.54) for ischemic stroke, and of 1.28 (1.08–1.53) for the combined endpoint. Conclusions High plasma ionized calcium is associated with higher risk of myocardial infarction and ischemic stroke compared to plasma ionized calcium within the reference interval.

Secular trends in risk of stroke according to body mass index and blood pressure, 1976–2017

Neurology ◽  
2019 ◽  
Vol 93 (14) ◽  
pp. e1397-e1407
Author(s):  
Julie Riis ◽  
Børge G. Nordestgaard ◽  
Gorm B. Jensen ◽  
Shoaib Afzal
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Body Mass Index ◽  
General Population ◽  
Body Mass ◽  
Secular Trends ◽  
Stroke Event ◽  
General Population Study ◽  
Hazard Ratios ◽  
Related Risk

ObjectiveTo test the hypothesis that the associations of body mass index (BMI) and BMI-related risk factors with risk of stroke have attenuated over time using cohorts recruited from the general population over 4 decades.MethodsWe undertook prospective studies of 2 cohorts enrolled in 1976 to 1978 (13,567 participants from the Copenhagen City Heart Study) and 2003 to 2015 (107,040 participants from the Copenhagen General Population Study). Each cohort was recruited randomly from the Danish general population 20 to 100 years of age. Participants were followed up from the date of examination to date of emigration, death, or stroke event, whichever occurred first. Follow-up ended in March 2017. We did not lose track of any individual. BMI and blood pressure were modeled with splines and in categories. Main outcome was incident stroke, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.ResultsThe crude incidence of stroke declined in extreme categories of BMI and blood pressure from 1977 to 2017. The multivariable-adjusted hazard ratios for stroke in participants with BMI ≥30 vs 18.5 to 24.9 kg/m2 were 1.4 (95% confidence interval 1.2–1.6) in the 1976–1978 cohort and 1.1 (1.0–1.2) in the 2003–2015 cohort (p = 0.008 for 1976–1978 vs 2003–2015). The corresponding hazard ratios (confidence intervals) in participants with blood pressure ≥160/100 vs <140/90 mm Hg were 2.1 (1.9–2.3) and 1.5 (1.4–1.7), respectively (p < 0.001). Similar secular trends were observed for diabetes mellitus but were not obvious for other risk factors.ConclusionThe associations of high BMI and high blood pressure with higher risk of stroke were attenuated across 2 Danish cohorts enrolled from 1976 through 2015.

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