In patients with heart failure (HF) who suffered in-hospital cardiac arrest (IHCA), little is known about the characteristics, survival and neurological outcome. We used the Swedish Registry of ...Cardiopulmonary Resuscitation to study this, including patients aged ≥ 18 years suffering IHCA (2008-2019), categorised as HF alone, HF with acute myocardial infarction (AMI), AMI alone, or other. Odds ratios (OR) for 30-day survival, trends in 30-day survival, and the implication of HF phenotype was studied. 6378 patients had HF alone, 2111 had HF with AMI, 4210 had AMI alone. Crude 5-year survival was 9.6% for HF alone, 12.9% for HF with AMI and 34.6% for AMI alone. The 5-year survival was 7.9% for patients with HF and left ventricular ejection fraction (LVEF) ≥ 50%, 15.4% for LVEF < 40% and 12.3% for LVEF 40-49%. Compared with AMI alone, adjusted OR (95% CI) for 30-day survival was 0.66 (0.60-0.74) for HF alone, and 0.49 (0.43-0.57) for HF with AMI. OR for 30-day survival in 2017-2019 compared with 2008-2010 were 1.55 (1.24-1.93) for AMI alone, 1.37 (1.00-1.87) for HF with AMI and 1.30 (1.07-1.58) for HF alone. Survivors with HF had good neurological outcome in 92% of cases.
Some aryl amide Schiff base Co(II), Ni(II) and Cu(II) distance between Cu(II) and complexes (
1
–
7
) have been obtained and identified by various analytical and spectroscopic tools. To through a ...light on the probability of structure changes with γ-irradiation, powder samples of complexes
1
,
3
,
5
and
6
were irradiated with
60
Co γ-rays at dose of 100 kGy (hereafter referred to as
1F
,
3F
,
5F
and
6F
). Spectral, molar conductance, magnetic susceptibility, thermal, X-ray diffraction and antioxidant activity for the irradiated complexes were gained using similar methods used for the non-irradiated complexes. The data revealed that the irradiated complexes were not seriously affected by the utilized γ-irradiation dose.
This review critically appraises studies examining the association of novel factors with diabetes. We show that many of the most studied novel and apparently 'independent' risk factors are correlated ...with each other by virtue of their common origins or pathways, and that residual confounding is likely. Available studies also have other limitations, including differences in methodology or inadequate statistical analyses. Furthermore, although most relevant work in this area has focused on improving our understanding of the pathogenesis of diabetes, association studies in isolation cannot prove causality; intervention studies with specific agents (if available) are required, and genetic studies may help. With respect to the potential value of novel risk factors for diabetes risk prediction, we illustrate why this work is very much in its infancy and currently not guaranteed to reach clinical utility. Indeed, the existence of several more easily measured powerful predictors of diabetes, suggests that the additional value of novel markers may be limited. Nevertheless, several suggestions to improve relevant research are given. Finally, we show that several risk factors for diabetes are only weakly associated with the risk of incident vascular events, an observation that highlights the limitations of attempting to devise unified criteria (e.g. metabolic syndrome) to identify individuals at risk of both CHD and diabetes.
There is intense interest in mechanisms whereby low-grade inflammation could interact with conventional and novel vascular risk factors to promote the atheromatous lesion. Patients with rheumatoid ...arthritis (RA), who by definition manifest persistent high levels of inflammation, are at greater risk of developing cardiovascular disease. Mechanisms mediating this enhanced risk are ill defined. On the basis of available evidence, we argue here that the systemic inflammatory response in RA is critical to accelerated atherogenesis operating via accentuation of established and novel risk factor pathways. By implication, long-term suppression of the systemic inflammatory response in RA should be effective in reducing risk of coronary heart disease. Early epidemiological observational and clinical studies are commensurate with this hypothesis. By contrast, risk factor modulation with conventional agents, such as statins, may provide unpredictable clinical benefit in the context of uncontrolled systemic inflammatory parameters. Unraveling such complex relationships in which exaggerated inflammation-risk factor interactions are prevalent may elicit novel insights to effector mechanisms in vascular disease generally.
The relationship between metabolic risk and time spent sitting, standing and stepping has not been well established. The present study aimed to determine associations of objectively measured time ...spent siting, standing and stepping, with coronary heart disease (CHD) risk.
A cross-sectional study of healthy non-smoking Glasgow postal workers, n=111 (55 office workers, 5 women, and 56 walking/delivery workers, 10 women), who wore activPAL physical activity monitors for 7 days. Cardiovascular risks were assessed by metabolic syndrome categorisation and 10-year PROCAM (prospective cardiovascular Munster) risk.
Mean (s.d.) age was 40 (8) years, body mass index 26.9 (3.9) kg m
and waist circumference 95.4 (11.9) cm. Mean (s.d.) high-density lipoprotein cholesterol (HDL cholesterol) 1.33 (0.31), low-density lipoprotein cholesterol 3.11 (0.87), triglycerides 1.23 (0.64) mmol l
and 10-year PROCAM risk 1.8 (1.7)%. The participants spent mean (s.d.) 9.1 (1.8) h per day sedentary, 7.6 (1.2) h per day sleeping, 3.9 (1.1) h per day standing and 3.3 (0.9) h per day stepping, accumulating 14 708 (4984) steps per day in 61 (25) sit-to-stand transitions per day. In univariate regressions-adjusting for age, sex, family history of CHD, shift worked, job type and socioeconomic status-waist circumference (P=0.005), fasting triglycerides (P=0.002), HDL cholesterol (P=0.001) and PROCAM risk (P=0.047) were detrimentally associated with sedentary time. These associations remained significant after further adjustment for sleep, standing and stepping in stepwise regression models. However, after further adjustment for waist circumference, the associations were not significant. Compared with those without the metabolic syndrome, participants with the metabolic syndrome were significantly less active-fewer steps, shorter stepping duration and longer time sitting. Those with no metabolic syndrome features walked >15 000 steps per day or spent >7 h per day upright.
Longer time spent in sedentary posture is significantly associated with higher CHD risk and larger waist circumference.
Insulin-loaded microemulsions made by a reverse micellar approach improve the oral bioavailability of insulin with modest effects on blood glucose levels in diabetic rats.
Insulin loaded ...microemulsions were developed adopting a low shear reverse micellar approach using didoceyldimethylammonium bromide (DMAB) as the surfactant, propylene glycol (PG) as the co-surfactant, triacetin (TA) as the oil phase and insulin solution as the aqueous phase. A ternary phase diagram was constructed based on multiple cloud point titration to highlight the reverse micellar region. The droplet sizes of the microemulsions were 161.7
±
24.7
nm with PDI of 0.447
±
0.076 and insulin entrapment of ∼85%. Transmission electron microscopy (TEM) revealed the spherical nature and size homogeneity of the microemulsion droplets. The conformational stability of the entrapped insulin within microemulsions was confirmed by fluorescence spectroscopy and circular dichroism. The microemulsions displayed a 10-fold enhancement in bioavailability compared with plain insulin solution administered
per oral in healthy rats. The short-term
in vivo efficacy in STZ induced diabetic rats provided the proof of concept by a modest glucose reduction at a dose of 20
IU/kg. Together this preliminary data indicate the promise of microemulsions for oral delivery of insulin.
Aims
To describe the prevalence of major cardiovascular disease (CVD) and risk factor control in a contemporary population with Type 2 diabetes.
Methods
We used data from the national registry in ...Scotland, Scottish Care Information‐Diabetes, linked to hospital admissions. Using descriptive statistics and logistic regression we described associations of risk factors with CVD. CVD was defined based on diagnostic codes in primary or secondary care data for ischaemic heart disease, cerebrovascular disease peripheral arterial disease, heart failure, cardiac arrhythmia, hypertensive heart disease and revascularization procedures.
Results
Among 248 400 people with Type 2 diabetes with a median age of 67.5 years (IQR 58.2, 76.1) and median diabetes duration of 7.8 years (3.8, 13.0), 32% had prior CVD (35% of men, 29% of women). Median HbA1c overall was 55 mmol/mol (7.2%), median SBP was 132 mmHg, median total cholesterol was 4.1 mmol/l and mean BMI was 32 kg/m2. Overall two‐thirds (65% of men, 68% of women) have two or more of the following CVD risk factor thresholds: HbA1c ≥ 53 mmol/mol (7%), SBP > 130 mmHg or DBP > 80 mmHg, total cholesterol ≥ 5 mmol/l or BMI ≥ 30 kg/m2, or were currently smoking. Overall 84% were taking anti‐hypertensives and 75% a statin. Use of metformin was common at 58%, but other diabetes drugs that reduce CVD were rarely used.
Conclusions
There continues to be a high prevalence of CVD among people with Type 2 diabetes and a high level of unmet need for risk factor control. This implies substantial scope for reducing the excess risk of CVD in diabetes through improved management of known risk factors.
What's new?
There have been substantial advances in the management and prevention of cardiovascular disease in diabetes. To understand where unmet needs lie, it is important to understand the current burden of cardiovascular disease and the levels of treated and untreated risk factors.
In this paper, we show that there continues to be a high prevalence of cardiovascular disease among people with Type 2 diabetes and a high level of unmet need for risk factor control. This implies substantial scope for reducing the excess risk of cardiovascular disease in diabetes through improved management of known risk factors.
Background
As opposed to the decreasing overall rates of coronary heart disease (CHD) incidence and overall cardiovascular disease (CVD) mortality, heart failure (HF) and stroke incidence are ...increasing in young people, potentially due to rising rates of obesity and reduced cardiorespiratory fitness (CRF).
Objectives
We investigated trends in early major CVD outcomes in a large cohort of young men.
Methods
Successive cohorts of Swedish military conscripts from 1971 to 1995 (N = 1,258,432; mean age, 18.3 years) were followed, using data from the National Inpatient and Cause of Death registries. Cox proportional hazard models were used to analyse changes in 21‐year CVD event rates.
Results
21‐year CVD and all‐cause mortality and incidence of acute myocardial infarction (AMI) decreased progressively. Compared with the cohort conscripted in 1971–1975 (reference), the hazard ratios (HRs) for the last 1991–1995 cohort were 0.50 95% confidence interval (CI) 0.42‐0.59 for CVD mortality; 0.57 (95% CI 0.54–0.60) for all‐cause mortality; and 0.63 (95% CI 0.53–0.75) for AMI. In contrast, the incidence of ischaemic stroke, intracerebral haemorrhage and HF increased with HRs of 1.43 (95% CI 1.17–1.75), 1.30 (95% CI 1.01–1.68) and 1.84 (95% CI 1.47–2.30), respectively. During the period, rates of obesity increased from 1.04% to 2.61%, whilst CRF scores decreased slightly. Adjustment for these factors influenced these secular trends only moderately.
Conclusion
Secular trends of young‐onset CVD events demonstrated a marked shift from AMI and CVD mortality to HF and stroke incidence. Trends were significantly, though moderately, influenced by changing baseline BMI and CRF.
GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic ...understanding is lacking
. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with β-thalassaemia, a condition in which GDF15 levels are chronically high
, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.
There is growing evidence that early development of obesity increases cardiovascular risk later in life, but less is known about whether there are effects of long-term excess body weight on the ...biological drivers associated with the atherosclerotic pathway, particularly adipokines, inflammatory and endothelial markers. This paper therefore investigates the influence of overweight across the life course on levels of these markers at retirement age.
Data from the Medical Research Council National Survey of Health and Development (n=1784) were used to examine the associations between overweight status at 2, 4, 6, 7, 11, 15, 20, 26, 36, 43, 53 and 60-64 years (body mass index (BMI)⩾25 kg m(-2) for adult ages and gender-specific cut-points for childhood ages equivalent to BMI⩾25 kg m(-2)) and measurements of adipokines (leptin and adiponectin), inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6)) and endothelial markers (E-selectin, tissue plasminogen activator (t-PA) and von Willebrand factor) at 60-64 years. In addition, the fit of different life course models (sensitive periods/accumulation) were compared using partial F-tests.
In age- and sex-adjusted models, overweight at 11 years and onwards was associated with higher leptin, CRP and IL-6 and lower adiponectin; overweight at 15 years and onwards was associated with higher E-selectin and t-PA. Associations between overweight at all ages earlier than 60-64 with leptin, adiponectin, CRP and IL-6 were reduced but remained apparent after adjustment for overweight at 60-64 years; whereas those with E-selectin and t-PA were entirely explained. An accumulation model best described the associations between overweight across the life course with adipokines and inflammatory markers, whereas for the endothelial markers, the sensitive period model for 60-64 years provided a slightly better fit than the accumulation model.
Overweight across the life course has a cumulative influence on adipokines, inflammatory and possibly endothelial markers. Avoidance of overweight from adolescence onwards is likely important for cardiovascular disease prevention.