Recent studies suggested obesity to be a possible risk factor for COVID-19 disease in the wake of the coronavirus (SARS-CoV-2) infection. However, the causality and especially the role of body fat ...distribution in this context is still unclear. Thus, using a univariable as well as multivariable two-sample Mendelian randomization (MR) approach, we investigated for the first time the causal impact of body composition on the susceptibility and severity of COVID-19.
As indicators of overall and abdominal obesity we considered the measures body mass index (BMI), waist circumference (WC), and trunk fat ratio (TFR). Summary statistics of genome-wide association studies (GWASs) for these body composition measures were drawn from the GIANT consortium and UK Biobank, while for susceptibility and severity due to COVID-19 disease data from the COVID-19 Host Genetics Initiative was used. For the COVID-19 cohort neither age nor gender was available. Total and direct causal effect estimates were calculated using Single Nucleotide Polymorphisms (SNPs), sensitivity analyses were done applying several robust MR techniques and mediation effects of type 2 diabetes (T2D) and cardiovascular diseases (CVD) were investigated within multivariable MR analyses.
Genetically predicted BMI was strongly associated with both, susceptibility (OR = 1.31 per 1 SD increase; 95% CI: 1.15–1.50; P-value = 7.3·10−5) and hospitalization (OR = 1.62 per 1 SD increase; 95% CI: 1.33–1.99; P-value = 2.8·10−6) even after adjustment for genetically predicted visceral obesity traits. These associations were neither mediated substantially by T2D nor by CVD. Finally, total but not direct effects of visceral body fat on outcomes could be detected.
This study provides strong evidence for a causal impact of overall obesity on the susceptibility and severity of COVID-19 disease. The impact of abdominal obesity was weaker and disappeared after adjustment for BMI. Therefore, obese people should be regarded as a high-risk group. Future research is necessary to investigate the underlying mechanisms linking obesity with COVID-19.
•Overall fat content has a causal impact on the susceptibility and severity of COVID-19.•These associations were neither mediated substantially by T2D nor by CVD.•Visceral fat content has no significant direct effect on the COVID-19 outcomes.
The question of whether asthma is causally related to gastrointestinal disorders remained unanswered so far. Thus, this study investigated whether there is such a relation and whether the time of ...onset of asthma plays a role in the occurrence of the following gastrointestinal disorders: peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) including the distinction between Crohn's disease (CD) and ulcerative colitis (UC).
Using summary data of genome-wide association studies (GWASs), we ran Mendelian randomization analyses based on up to 456,327 European participants. Outlier assessment, a series of sensitivity analyses and validation of IBD results in a second GWAS were performed to confirm the results.
Presented ORs represent the average change in the outcome per 2.72-fold increase in the prevalence of the exposure. Genetically predicted childhood-onset asthma was positively associated with PUD, GORD, and IBS with similar odds ratios near 1.003 and adjusted P-values from 0.007 (GORD) to 0.047 (PUD). Furthermore, it was inversely related to IBD (OR = 0.992, 95% CI: 0.986, 0.998, adjusted P = 0.023) and suggestively associated with its UC subtype (OR = 0.990, 95% CI: 0.982, 0.998, adjusted P = 0.059). There were no associations between genetically predicted adult-onset asthma and the mentioned gastrointestinal disorders.
This study provides evidence that the presence of asthma onset in childhood increases the risk for GORD, PUD, and IBS but decreases the risk for IBD in adults. The lower risk for IBD may be attributed to a lower risk primarily for UC.
Abstract Muscular strength, an important component of physical fitness, has an independent role in the prevention of chronic diseases whereas muscular weakness is strongly related to functional ...limitations and physical disability. Our purpose was to investigate the role of muscular strength as a predictor of mortality in health and disease. We conducted a systematic search in EMBASE and MEDLINE (1980–2014) looking for the association between muscular strength and mortality risk (all-cause and cause-specific mortality). Selected publications included 23 papers (15 epidemiological and 8 clinical studies). Muscular strength was inversely and independently associated with all-cause mortality even after adjusting for several confounders including the levels of physical activity or even cardiorespiratory fitness. The same pattern was observed for cardiovascular mortality; however more research is needed due to the few available data. The existed studies failed to show that low muscular strength is predictive of cancer mortality. Furthermore, a strong and inverse association of muscular strength with all-cause mortality has also been confirmed in several clinical populations such as cardiovascular disease, peripheral artery disease, cancer, renal failure, chronic obstructive pulmonary disease, rheumatoid arthritis and patients with critical illness. However, future studies are needed to further establish the current evidence and to explore the exact independent mechanisms of muscular strength in relation to mortality. Muscular strength as a modifiable risk factor would be of great interest from a public health perspective.
The present study evaluated the ability of the visceral adiposity index (VAI), the lipid accumulation product (LAP), and product of triglycerides and glucose (TyG), three novel, insulin ...resistance-related markers, to discriminate prediabetes/diabetes in the general German population. Altogether 2,045 Germans (31-72 years, 53.3% women) without known diabetes and a history of Myocardial Infarction (MI)/stroke from the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study were eligible. The discriminatory accuracy of the markers for oral glucose tolerance test (OGTT)-defined prediabetes/diabetes according to the American Diabetes Association (ADA) criteria was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). The Youden Index (YI) was used to determine optimal cut-off values, and a non-parametric ROC regression was used to examine whether the discriminatory accuracy varied by sex and age. 365 men (38.2%) and 257 women (23.6%) were newly diagnosed with prediabetes/diabetes. AUCs for TyG, LAP and VAI were 0.762 (95% CI 0.740-0.784), 0.743 (95% CI 0.720-0.765), and 0.687 (95% CI 0.662-0.712), respectively. The optimal cut-off values for the LAP and TyG were 56.70 and 8.75 in men, and 30.40 and 8.53 in women. In conclusion, TyG and LAP provide good discrimination of persons with prediabetes/diabetes.
Abstract
Limited data on prehospital and early in-hospital coronary heart disease (CHD) deaths is available. Aims of this study were to provide a comprehensive description on CHD cases and to analyse ...determinants of prehospital death. From a population-based myocardial infarction (MI) registry in Augsburg, Germany we included 12,572 CHD cases aged 25–74 years between 2003–2017 and 4754 CHD cases aged 75–84 years between 2009–2017. Multivariable logistic regression models were conducted to identify patient characteristics associated with prehospital death compared to 28-day survival. In patients aged 25–74 years, 1713 (13.6%) died prehospital, 941 (7.5%) died within the first 24 h in-hospital and 560 (4.5%) died within the 2nd and 28th day after the acute event; in patients aged 75–84 years the numbers were 1263 (26.6%), 749 (15.8%) and 329 (6.9%), respectively. In both age groups increasing age, actual smoking or nicotine abuse, previous MI, angina pectoris and previous stroke were more likely and hypertension was less likely in cases, who died prehospital compared to 28-day survivors. For example, in the 25–74 years old we revealed an adjusted odds ratio (OR) of 4.53 (95% CI 3.84–5.34) for angina pectoris and an OR of 0.69 (95% CI 0.57–0.85) for hypertension. In cases aged 25–74 years, an association of living alone (OR 1.26, 95% CI 1.06–1.49) and diabetes (OR 1.20, 95% CI 1.03–1.41) with prehospital death was found. Whereas in cases aged 75–84 years, chronic obstructive pulmonary disease (OR 2.20, 95%CI 1.69–0.2.85) was associated with prehospital death. In summary, we observed high prehospital and early in-hospital case fatality. Besides classical cardiac risk factors, the impact of living alone on prehospital death was more important in patients aged 25–74 years than in older patients.
Calcium plays an essential role in physiology of the cardiovascular system. Aberrations from normal serum calcium levels are known to be associated with several cardiovascular diseases. Its possible ...role as a predictor for long-term mortality after acute myocardial infarction (AMI) is still uncertain. In this study, a total of 3732 patients (aged 25-74 years) with incident AMI surviving at least 28 days after AMI was included. The median follow-up time was 6.0 years. Admission total serum calcium levels were divided into quartiles. The Kaplan-Meier-Curve suggested a division of the follow up time in two different time periods. So, Cox regression models were calculated to assess association between admission serum calcium levels and all-cause long-term mortality with two observation periods: 28-2500 days and > 2500 days. The final model was adjusted for various comorbidities, clinical characteristics, in-hospital treatment and medication. The third quartile (normal-high Calcium levels) served as the reference group. The fully adjusted Cox-regression model shows significantly higher mortality risk for low serum calcium (quartile 1) within the timeframe 28-2500 days after the event (OR 1.53 1.19-1.98). The other groups did not differ significantly from each other. In the later observation period (from 2500 days until death or censoring) no more significant differences were seen between the four calcium quartiles. In summary, low serum calcium is an independent predictor of adverse outcome in the first 2500 days (about 7 years) after AMI. On later points in time this effect attenuates, so that no more significant differences can be observed.
Abstract
Background
Hypertension remains a significant modifiable risk factor for cardiovascular diseases and a major determinant of morbidity and mortality. We aimed to describe sex-stratified ...age-standardized estimates of prevalence, awareness, treatment and control of hypertension, and their associated factors in older adults.
Methods
The KORA-Age1 is a population-based cross-sectional survey carried out in 2008/2009 on individuals aged 65–94 years in Augsburg region, Germany. Blood pressure measurements were available for 1052 out of 1079 persons who participated in the physical examination. Factors associated with prevalence, awareness and control of hypertension were investigated by multivariable logistic regression.
Results
The overall prevalence of hypertension (≥140/90 mmHg) was 73.8% 95% confidence interval (CI), 69.3–77.9, representing 74.8% (95% CI, 68.4–80.2) in men and 73.5% (95% CI, 66.8–79.3) in women. Among those with hypertension, 80.2% (95% CI, 75.3–84.4) were aware of their hypertensive condition and 74.4% (95% CI, 69.2–79.1) were on treatment for hypertension. Among those aware of their hypertension status, 92.8% (95% CI, 88.8–95.6) were on treatment and 53.7% (95% CI, 47.0–60.1) had their blood pressure controlled. Hypertension was more frequent in individuals who were older, obese, or had diabetes. Higher education attainment or presence of comorbidities was associated with higher level of hypertension awareness. Individuals taking three antihypertensive drug classes were more likely to have controlled hypertension compared with those taking one antihypertensive drug class, odds ratio (OR), 1.85 (95% CI, 1.14–2.99).
Conclusion
Our findings identified high prevalence of hypertension and relevant health gaps on awareness, treatment and suboptimal control of hypertension in older adults in Germany. Screening for hypertension should especially target older adults with low educational attainment and ‘healthy’ elderly with less contact to physicians.
Abstract
Aims
The association between air temperature and mortality has been shown to vary over time, but evidence of temporal changes in the risk of myocardial infarction (MI) is lacking. We aimed ...to estimate the temporal variations in the association between short-term exposures to air temperature and MI in the area of Augsburg, Germany.
Methods and results
Over a 28-years period from 1987 to 2014, a total of 27 310 cases of MI and coronary deaths were recorded. Daily meteorological parameters were measured in the study area. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the risk of MI associated with air temperature. Subgroup analyses were performed to identify subpopulations with changing susceptibility to air temperature. Results showed a non-significant decline in cold-related MI risks. Heat-related MI relative risk significantly increased from 0.93 95% confidence interval (CI): 0.78–1.12 in 1987–2000 to 1.14 (95% CI: 1.00–1.29) in 2001–14. The same trend was also observed for recurrent and non-ST-segment elevation MI events. This increasing population susceptibility to heat was more evident in patients with diabetes mellitus and hyperlipidaemia. Future studies using multicentre MI registries at different climatic, demographic, and socioeconomic settings are warranted to confirm our findings.
Conclusion
We found evidence of rising population susceptibility to heat-related MI risk from 1987 to 2014, suggesting that exposure to heat should be considered as an environmental trigger of MI, especially under a warming climate.
Prior studies examined association between short-term mortality and certain changes in the admission ECG in acute myocardial infarction (AMI). Nevertheless, little is known about possible differences ...between patients with diabetes and without diabetes in this regard. So the aim of the study was to investigate the association between 28-day case fatality according to certain ECG changes comparing AMI cases with and without diabetes from the general population. From 2000 until 2017 a total of 9756 AMI cases was prospectively recorded in the study Area of Augsburg, Germany. Each case was assigned to one of the following groups according to admission ECG: 'ST-elevation', 'ST-depression', 'only T-negativity', 'predominantly bundle branch block', 'unspecific changes' and 'normal ECG' (the last two were put together for regression analyses). Multivariable adjusted logistic regression models were calculated to compare 28-day case-fatality between the ECG groups for the total sample and separately for diabetes and non-diabetes cases. For the non-diabetes group, the parsimonious logistic regression model revealed significantly better 28-day-outcome for the 'normal ECG / unspecific changes' group (OR: 0.47 0.29-0.76) compared to the reference group (STEMI). Contrary, in AMI cases with diabetes the category 'normal ECG / unspecific changes' was not significantly associated with lower short-term mortality (OR: 0.87 0.49-1.54). Neither of the other ECG groups was significantly associated with 28-day-mortality in the parsimonious logistic regression models. Consequently, the absence of AMI-typical changes in the admission ECG predicts favorable short-term mortality only in non-diabetic cases, but not so in patients with diabetes.
Recent studies focused on modulating factors of paraoxonase-1 (PON1) activity. In some studies the association between pro-inflammatory markers and PON1 activity was examined, but so far no ...population-based investigations on this issue have been conducted. The present study investigated the relationships between the pro-inflammatory markers tumor necrosis factor (TNF)-α, leptin, interleukin (IL)-6, and high-sensitive C-reactive protein (hs-CRP) and paraoxonase and arylesterase, two hydrolytic activities of PON1, in the population-based Bavarian Food Consumption Survey II.
Based on 504 participants (217 men, 287 women), the relationship between the pro-inflammatory markers and the outcomes paraoxonase and arylesterase activities were investigated using multivariable linear models.
Circulating plasma levels of leptin (P-value < 0.0001), hs-CRP (P-value = 0.031) and IL-6 (P-value = 0.045) were significantly non-linearly associated with arylesterase activity. Leptin levels were also significantly associated with paraoxonase activity (P-value = 0.024) independently from confounding factors, including high-density lipoprotein (HDL) cholesterol. With increasing levels of these inflammatory parameters, arylesterase and paraoxonase activities increased; however, at higher levels (> 75th percentile) the activities reached a plateau or even decreased somewhat. After Bonferroni-Holm correction, only leptin remained non-linearly but significantly associated with arylesterase activity (adjusted overall P-value < 0.0001). Neither age nor sex nor obesity modified the associations. No association was found between TNF-α and paraoxonase or arylesterase activity.
The present findings suggest that in persons with very high levels of inflammation, PON1 activity may be impaired, a fact that might subsequently be accompanied by a higher risk for cardiometabolic diseases. Whether or not the measurement of PON1 activity in combination with a lipid profile and certain inflammatory markers could improve the prediction of cardiometabolic diseases in middle-aged individuals from the general population should be evaluated in clinical studies.
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