Orthostatic hypotension and the risk of atrial fibrillation and other cardiovascular diseases: An updated meta‐analysis of prospective cohort studies

The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta‐analysis was conducted in hopes of producing progress on this topic. A systematic database search was performed in electronic databases, including the Chinese Biomedical Database (CBM), PubMed, Web of Science, and the Cochrane Library. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by a random‐effects model. Statistical heterogeneity was assessed with Cochran's Q test and the I² statistic. From 1462 potentially eligible records, 15 studies met the inclusion criteria. Subjects with OH had a high risk of heart failure (HF) and atrial fibrillation (AF) (pooled HR 1.34, 95% CI 1.17‐1.52, P < 0.001 and pooled HR 1.51, 95% CI 1.28‐1.79, P < 0.001, respectively). This meta‐analysis also showed significant associations between OH and the risks of developing coronary heart disease (CHD) (pooled HR 1.44, 95% CI 1.18‐1.75, P < 0.001) and myocardial infarction (MI) (pooled HR 1.52, 95% CI 1.12‐2.06, P = 0.008). Our study suggests that OH is positively associated with high risks of HF and AF. Moreover, it may be related to high risks of CHD and MI.     

Cardiovascular risk factor management is poorer in diabetic patients with undiagnosed peripheral arterial disease than in those with known coronary heart disease or cerebrovascular disease. Results of a nationwide study in tertiary diabetes centres

Aims To assess whether patients with Type 2 diabetes mellitus and unrecognized peripheral arterial disease (PAD), detected by the ankle–brachial index (ABI), have poorer cardiovascular risk factor management (CVRFs) and receive fewer medications than patients previously diagnosed with coronary heart disease (CHD) or cerebrovascular disease (CVD). Methods In 31 diabetes centres throughout Spain, 1303 patients with Type 2 diabetes mellitus were screened for PAD using the ABI. Patient history of CHD and CVD and treatment and control of CVRFs were recorded. Results Forty-one patients had an ABI > 1.30 and were excluded, leaving 1262 patients (age 65.3 ± 7.7 years) for the study. Of those screened, 790 patients had a normal ABI (ABI > 0.9) and no known history of CHD or CVD (no CHD/CVD/PAD group), 194 had unrecognized PAD (ABI ≤ 0.9) with no known history of CHD or CVD (undiagnosed PAD group) and 278 had a known history of CHD and/or CVD (CHD/CVD group). The undiagnosed PAD group had higher low-density lipoprotein (LDL) cholesterol (2.9 ± 0.83 vs. 2.4 ± 0.84 mmol/l; P < 0.001) and systolic blood pressure (150 ± 20 vs. 145 ± 21 mmHg; P < 0.001) compared with the CHD/CVD group. They were less likely to take statins (56.9 vs. 71.6%; P < 0.001), anti-hypertensive agents (75.9 vs. 90.1%, P = 0.001), and anti-platelet agents (aspirin, 28.7 vs. 57.2%; P < 0.001; clopidogrel, 5.6 vs. 20.9%; P < 0.001) and more likely to smoke (21.0 vs. 9.2%; P < 0.001). Higher LDL in the undiagnosed PAD group was associated with the underutilization of statins. Conclusions Measurement of ABI detected a significant number of patients with PAD, who did not have CHD or CVD, but whose CVRFs were under treated and poorly controlled compared with subjects with CHD and/or CVD.     

Hypercholesterolaemia and risk of coronary heart disease in the elderly: Impact of age: The Copenhagen City Heart Study

BackgroundPopulation and interventional studies have shown that high plasma-cholesterol is a risk factor of coronary heart disease (CHD). However, in most of the studies elderly people were excluded.AimThis paper assesses whether the effect of total plasma-cholesterol on the risk of incident CHD decreases with age in a healthy population.MethodsWithin the Copenhagen City Heart Study in 1981–1983, 4647 men and 5829 women, aged 40–93 years, underwent a cardiovascular health examination including measurement of plasma-cholesterol. The cohort was followed with respect to incident CHD until 1994, i.e. before statins were introduced in Denmark.ResultsIn people below 60 years of age plasma-cholesterol levels on 5–6; 6–8; and > 8 mmol/L were associated with relative risks of CHD on 2.0 (95% confidence interval (CI) 1.2–3.2, P = 0.004); 3.1 (CI 2.0–5.0, P < 0.001); and 5.1 (CI 2.8–9.3, P < 0.001), respectively (reference group: plasma-cholesterol < 5 mmol/L). In people aged 60–70 years a plasma-cholesterol level on 5–6 mmol/L was not associated with increased risk, whereas plasma-cholesterol on 6–8 mmol/L and > 8 mmol/L was associated with relative risks on 1.3 (CI 1.0–1.8, P = 0.03), and 2.3 (CI 1.6–3.4, P < 0.001), respectively. In people aged 70–80 years only plasma-cholesterol > 8 mmol/L conferred increased relative risk on 1.6 (CI 1.2–2.4, P = 0.007). In people above 80 years of age increased plasma-cholesterol was not associated with increased risk of incident CHD.ConclusionThe risk of incident CHD associated with high plasma-cholesterol declines with age.This finding should be considered in future recommendations of plasma-cholesterol levels in elderly people without atherosclerotic cardiovascular disease.     

Association between birth weight and risk of cardiovascular disease: Evidence from UK Biobank

Background and aimsBirth weight has been linked to cardiovascular disease (CVD) risk in adulthood, but no consensus has emerged on the threshold of birth weight for the lowest CVD risk and few studies have examined potential interaction between birth weight and adult adiposity.Methods and resultsA total of 256,787 participants, who had birth weight data and were free of CVD at baseline, were included from UK Biobank. Multivariate restricted cubic splines and Cox regression models were used to assess the association between birth weight and CVD. We observed nonlinear inverse associations of birth weight with the risk of coronary heart disease (CHD), stroke, and heart failure. Participants with the first quintile of birth weight (≤2.85 kg) had higher risks for CHD (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.15–1.32), stroke (HR = 1.19, 95% CI: 1.03–1.37), and heart failure (HR = 1.28, 95% CI: 1.11–1.48), as compared to the fourth quintile (3.41–3.79 kg). There was a significant interaction between birth weight and adult body mass index (BMI) on CHD and heart failure (both P for interaction <0.001), showing the highest risk for those who had birth weight ≤2.85 kg and BMI ≥30 kg/m² (HR = 1.96, 95% CI: 1.70–2.25 and HR = 2.39, 95% CI: 1.77–3.22, respectively).ConclusionsOur findings indicate nonlinear inverse associations between birth weight and CVD risk, with a threshold of 3.41–3.79 kg for the lowest risk. Moreover, low birth weight may interact with adult obesity to increase the risk of CHD and heart failure.     

Risk factor control in patients with Type 2 diabetes and coronary heart disease: findings from the Swedish National Diabetes Register (NDR)

Aims Patients with Type 2 diabetes and coronary heart disease (CHD) are infrequently treated to risk factor targets in current guidelines. We aimed to examine risk factor management and control levels in a large sample of patients with Type 2 diabetes with CHD. Methods This was an observational study of 1612 patients with first incidence of CHD before 2002, and of 4570 patients with first incidence of CHD before 2005, from the Swedish National Diabetes Register (NDR). Results In patients with CHD 1–2 years before follow‐up, the achievement of cardiovascular risk factor targets (follow‐up 2002/follow‐up 2005) was: HbA_1c < 7%, 47%/54% (P < 0.01); blood pressure ≤ 130/80 mmHg, 31%/40% (P < 0.001); total cholesterol < 4.5 mmol/l, 47%/60% (P < 0.001); and low‐density lipoprotein‐cholesterol < 2.5 mmol/l, 49%/65% (P < 0.001). Use of medication: antihypertensives, 90%/94% (P < 0.01); lipid‐lowering drugs, 75%/86% (P < 0.001); and aspirin, 85%/89% (P < 0.05). A high prevalence of adverse lifestyle characteristics prevailed (2002/2005): overweight [body mass index (BMI) ≥ 25 kg/m²], 86%/85%; obesity (BMI ≥ 30 kg/m²), 41%/42%; smokers in age group < 65 years, 16–23%/18–19%; as well as waist circumference ≥ 102 cm (men) or ≥ 88 cm (women), 68% in 2005. Conclusions Patients with a combination of Type 2 diabetes and CHD showed an increased use of lipid‐lowering drugs over time, corresponding to improving blood lipid levels. A discrepancy existed between the prevalent use of antihypertensive drugs and the low proportion reaching blood pressure targets. Regretfully, a high prevalence of adverse lifestyle characteristics prevailed. Evidence‐based therapy with professional lifestyle intervention and drugs seems urgent for improved quality of secondary prevention in these patients.     

Association between leukocyte mitochondrial DNA content and risk of coronary heart disease: A case-control study

Objective

Compelling epidemiological evidence indicates that alterations of mitochondrial DNA (mtDNA), including mutations and abnormal content of mtDNA, are associated with the initiation and development of cardiovascular disease. This study was undertaken to investigate whether mtDNA content in peripheral blood leukocytes (PBLs) could be used as a risk predictor for coronary heart disease (CHD).

Methods

The mtDNA content of PBLs from 378 CHD patients and 378 matched healthy controls was measured using quantitative real-time PCR-based method in a case-control study. An unconditional multivariate logistic regression model was applied to estimate the association between leukocyte mtDNA content and CHD risk.

Results

CHD patients exhibited notably lower mtDNA content than matched healthy controls (median, 0.65 vs. 0.86; P < 0.001). Compared with individuals who had high mtDNA content, individuals who had low mtDNA content had a significantly increased risk of CHD (adjusted OR, 2.38; 95% confidence interval, 1.33–4.69). A significant dose–response relation was observed between increased CHD risk and lower mtDNA content (P_trend < 0.001). Furthermore, there was a significantly positive mtDNA content correlation between PBLs and atherosclerotic plaque tissue (ρ = 0.627, P = 0.039). In addition, a significant joint effect on the risk of CHD was noted between mtDNA content and cigarette smoking or plasma LDL-C concentration.

Conclusions

This present study provide the first epidemiologic evidence linking low mtDNA content in PBLs to an increased CHD risk, which warrants further investigation in other populations.     

Pulse pressure strongly predicts cardiovascular disease risk in patients with type 2 diabetes from the Swedish National Diabetes Register (NDR)

ObjectivesTo analyze pulse pressure (PP) as a risk predictor for coronary heart disease (CHD), stroke and cardiovascular disease (CVD; CHD and/or stroke) in type 2 diabetic patients.MethodsA total of 11,128 female and male type 2 diabetic patients with known baseline PP values and no CVD, aged 50–74 years, were followed for a mean duration of 5.6 years (1998–2003). A subgroup of 5521 patients with known mean PP values (mean values at baseline and at the end of the study) was also included.ResultsHazard ratios (HRs) with 95% CI for fatal/nonfatal CHD with baseline or mean PP ≥ 75 mmHg, compared to < 75 mmHg, were 1.23 (1.07–1.40; P = 0.003) and 1.32 (1.07–1.62; P = 0.009), respectively, after adjusting for mean blood pressure (MBP), age, gender, diabetes duration, HbA_1c, body mass index (BMI), lipid-reducing drugs, microalbuminuria > 20 μg/min, antihypertensive drugs and hypoglycaemic treatment, using Cox regression analyses. Fully-adjusted respective HRs for stroke were 1.17 (0.98–1.39) and 1.21 (0.90–1.61) and, for CVD, 1.23 (1.10–1.37; P < 0.001) and 1.28 (1.07–1.52; P = 0.007). Fully-adjusted HRs for baseline PP increased per quartile and, CHD, stroke or CVD, were 1.09 (1.03–1.16; P = 0.004), 1.14 (1.05–1.23; P = 0.002) and 1.11 (1.05–1.17; P < 0.001), respectively. The data suggest that, if a mean PP ≥ 75 mmHg were to be avoided, then 15% and 17% of CHD and or CVD, cases, respectively, in such a cohort might be prevented after multivariable adjustments, with a further 10% of cases avoided if also adjusted for MBP and age. Increasing baseline MBP, age and microalbuminuria were independently and significantly associated (P < 0.001) with increasing baseline or mean PP.ConclusionIncreased PP is a powerful independent risk predictor of CVD in type 2 diabetic patients, and lowering PP can lead to a marked reduction in risk.     

Interaction of angiotensin-converting enzyme and apolipoprotein E gene polymorphisms in ischemic stroke involving large-vessel disease

A relationship between apolipoprotein E (Apo E) genotype and angiotensin-converting enzyme (ACE) insertion-deletion (Ins-Del) mutation and stroke was suggested. We investigated the association of Apo E4 and ACE Ins/Del genotypes with stroke risk and changes in serum lipids in 228 consecutive Tunisian stroke patients, and 323 age-and gender-matched controls. Comparable frequencies of ACE Ins/Del alleles were seen between patients and controls. The prevalence of Apo ε3 allele and Apo E3/E3 were lower (P < 0.001), while the frequency of Apo ε4 allele and ε4-containing genotypes (E3/E4 and E4/E4) were elevated (P < 0.001) among patients. Higher proportion of Apo E4-carrying + ACE Del/Del positive cases were seen in young (<50 years) patients (P = 0.012), and was associated with large vessel stroke (P = 0.035). Mean serum cholesterol, LDL, HDL, and triglycerides were comparable between E4-containing and no E4-containing and ACE Del/Del-positive patients. Apo E4 and ACE Del/Del genotype combination substantially increase stroke risk, supporting the notion that interactions of multiple gene variants influence stroke pathogenesis.     

Dietary calcium intake and the risk of stroke: Meta-analysis of cohort studies

Background and aimsProspective cohorts are inconsistent regarding the association between dietary calcium intake and the risk of stroke. The aim was to perform a meta-analysis to determine whether an association exists between them in cohort studies.Methods and resultsRelevant studies were identified by searching PubMed, EMBASE and Web of Science databases that published before December 2022. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association were included. Study-specific risk estimates were combined by using a random effects model. Eighteen prospective studies, including 19,557 stroke cases among 882,181 participants, were pooled in the meta-analysis. We observed a nonlinear association between calcium intake and risk of stroke (P_nonlinearity < 0.003). Compared with the lowest value of zero assumed as the reference, the RRs (95% CI) of stroke across levels of calcium intake were 0.95 (0.92, 0.98) for 200 mg/day, 0.94 (0.90, 0.98) for 300 mg/day, 0.95 (0.90, 0.99) for 500 mg/day, 0.98 (0.93, 1.03) for 700 mg/day, and 1.04 (0.97, 1.11) for 1000 mg/day. The stratified analyses by geographic region showed nonlinear associations and indicated that the protective effect was observed in Asian countries (P_nonlinearity = 0.001) but not in non-Asian regions (P_nonlinearity = 0.047).ConclusionThis meta-analysis suggests that dietary calcium intake might play an effective role in the prevention of stroke, especially in Asian countries. Future research among Asia population should attempt to establish whether this association is causal.Systematic review registrationPROSPERO CRD42022357710.     

Consumption of nuts and legumes and risk of stroke: A meta-analysis of prospective cohort studies

Background and aimThe relationships between dietary nuts and legume intake and risk of stroke are inconsistent. We summarized the evidence by a meta-analysis of prospective cohort studies.Methods and resultsWe systematically searched the MEDLINE and EMBASE databases up to 31 January 2014. Random-effects models were used to calculate summary relative risks (SRRs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using the Cochran's Q and I² statistics.Eight prospective studies with a total of 468,887 subjects and 10,493 stroke events were included in the meta-analysis. Overall, a diet containing greater amounts of legumes may be not associated with a lower risk of stroke (SRR = 0.95, 95% CI: 0.84–1.08; P_{heterogeneity} = 0.091, I² = 43.2%); however, a diet containing greater amounts of nuts may be associated with a lower risk of stroke (SRR = 0.90, 95% CI: 0.81–0.99; P_{heterogeneity} = 0.527, I² = 0). Gender significantly modified the effects of nut consumption on stroke risk, and high nut intake was associated with reduced risk of stroke in women (SRR = 0.85, 95% CI: 0.75–0.97) other than in men (SRR = 0.95, 95% CI: 0.82–1.11).ConclusionThe current meta-analysis provides some evidences for the hypothesis that high intake of dietary nut was inversely associated with stroke risk, whereas dietary legumes intake was not associated with stroke risk.     

The effect of PCSK9 inhibitors on brain stroke prevention: A systematic review and meta-analysis

Background and aimsAlthough proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention.Methods and resultsWe searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67–0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84–1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66–1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81–1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times.ConclusionsPCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment.     

Metabolic syndrome and vascular risk: a 9-year follow-up among the aged in Finland

The aim was to analyze the relationship between metabolic syndrome (MetS) and vascular risk among the aged. A prospective population-based study, with a 9-year follow-up. All subjects of the municipality of Lieto in Finland aged ≥64 in 1998–99 participated (n = 1183). Hazard ratios (HRs) for fatal or non-fatal coronary (CHD), cerebrovascular (CV), or all vascular events predicted by MetS (defined by International Diabetes Federation) were estimated. During the 9-year follow-up, a total of 348 vascular events occurred, including 208 CHD and 150 CV events. After multivariable adjustment, CHD events (1.70, 1.07–2.71, P = .026) and vascular events (1.57, 1.07–2.30, P = .021) were more common in men with MetS compared to men without it. Evaluating MetS components individually, low HDL-cholesterol among women predicted a higher occurrence of CV (2.44, 1.46–4.09, P < .001) and all vascular (1.78, 1.26–2.53, P = .001) events. Elevated blood pressure among men was related to fewer CHD events (0.46, 0.25–0.83, P = .010). Our findings suggest that MetS does predict vascular events in late life among men. In older women, only low HDL-cholesterol was associated with vascular risk. Slightly or moderately elevated blood pressure values do not predict vascular events in this age group.     

Decreased serum netrin-1 is associated with ischemic stroke: A case–control study

Background and aimsNetrin-1 was a laminin-related protein involved in neurovascular protection, and we previously discovered that decreased serum netrin-1 was associated with poor prognosis of ischemic stroke. However, the relationship between serum netrin-1 level and the risk of ischemic stroke remains unclear. The aim of this study was to investigate the association between netrin-1 level and risk of ischemic stroke.Methods and resultsA case–control study including 591 ischemic stroke patients and 591 age- and sex-matched healthy individuals was conducted, and serum netrin-1 concentrations were quantitatively determined via enzyme-linked immunosorbent assay for all participants. The serum netrin-1 levels were significantly lower in the ischemic stroke patients than those in matched controls (median, 496.4 vs 652.1 pg/mL; P < 0.001). After adjustment for potential confounders, the odds ratio of ischemic stroke associated with the highest quartile of netrin-1 was 0.07 (95% CI: 0.01–0.65; P_trend = 0.018) compared with the lowest quartile of netrin-1. Each 1-standard deviation increase of log-transformed netrin-1 was associated with a lower odds of ischemic stroke (odds ratio: 0.45, 95% CI: 0.22–0.94; P = 0.032), and a dose–response relationship between serum netrin-1 and ischemic stroke was observed (P_linearity = 0.003). Incorporating netrin-1 to conventional risk factors improved the discriminatory power for ischemic stroke (net reclassification index = 98.0%, P < 0.001; integrated discrimination improvement = 0.28%, P = 0.027).ConclusionsSerum netrin-1 was decreased in patients with ischemic stroke compared with healthy controls, suggesting that there was a potential role of netrin-1 in the pathogenesis of ischemic stroke.     

Insulin sensitivity in Type 1 diabetic children and adolescents

Aim To estimate insulin sensitivity in Type 1 diabetic children and adolescents, and assess the relationship between insulin sensitivity and clinical markers of adiposity and parameters of the metabolic syndrome. Methods A total of 202 patients aged 8–18 years with Type 1 diabetes and disease duration 1.5–15 years participated. Insulin sensitivity was estimated by glucose uptake during an euglycaemic–hyperinsulinaemic clamp and was calculated as the average amount of glucose (M_lbm = mg/kg_lbm/min) required to maintain euglycaemia. Blood pressure, glycated haemoglobin (HbA_1c) and lipid concentrations were measured. Results The M_lbm value ranged from 4.14 to 25.25 mg/kg_lbm/min (mean 9.81 ± 3.34 mg/kg_lbm/min). There was a significant relationship between M value and patients’ age (r = –0.38, P < 0.0001). Insulin sensitivity decreased significantly with the onset of puberty; hence, it was significantly lower in pubertal and post‐pubertal adolescents. Girls were significantly more insulin resistant than boys (9.01 ± 0.32 vs. 10.43 ± 0.29 mg/kg_lbm/min, P = 0.005). Insulin sensitivity correlated with body mass index (r = –0.29, P < 0.001), waist circumference (r = –0.35, P < 0.001), triceps skin fold (r = –0.17, P = 0.018), subscapular skin fold (r = –0.23, P = 0.001) and body fat (r = –0.19, P = 0.006). There was a relationship between M_lbm value, cholesterol (r = –0.18, P = 0.012), high‐density lipoprotein cholesterol (r = 0.15, P = 0.035), low‐density lipoprotein cholesterol (r = –0.22, P = 0.002), triglycerides (r = –0.32, P < 0.001) and systolic blood pressure (r = –0.15, P = 0.029). Insulin resistance was related to HbA_1c (r = –0.18, P = 0.012). Additionally, there was a correlation between M_lbm value and insulin dose. Conclusions Children and adolescents with Type 1 diabetes mellitus have a very wide range of insulin sensitivity, which is determined by sex, age, amount of adipose tissue and glycaemic control.     

Epidemiology and risk factors for infections in myelodysplastic syndromes

We conducted a case–control study to describe the epidemiology and risk factors for infections requiring hospitalization in patients with myelodysplastic syndromes (MDS). Of 497 patients identified, 103 patients developed 201 episodes of infection. The probability of acquiring an infection 1 year from date of MDS diagnosis was 15% (95% confidence interval [CI] 12–18%). Patients developing infections had decreased survival compared to those who did not (P = 0.007). Significant risk factors for infection were higher risk MDS (hazard ratio [HR] = 2.7, 95% CI = 1.7–4.1, P < 0.0001), nadir absolute neutrophil count <500/mL (HR = 1.8, 95% CI = 1.2–2.7, P < 0.007), chronic obstructive pulmonary disease (HR = 2.6, 95% CI = 1.4–4.9, P < 0.003), history of other malignancy (HR 2.0, 95% CI = 1.3–3.1, P < 0.003), and autoimmune disease (HR 2.9, 95% CI = 1.4–6.0, P < 0.005). Age, nadir platelet count <20,000/mL, diabetes mellitus, and MDS treatment were not significant risk factors. Pneumonia was the most common infection, and bacteria the predominant pathogens.     

Low molecular weight heparin bridging for atrial fibrillation: is VTE thromboprophylaxis the major benefit?

Paucity of data has led to a lack of consensus regarding indications for, and risk–benefit ratio of, low molecular weight heparin ‘bridging’ for cardioembolic prevention in patients with atrial fibrillation (AF) until their INR levels are in therapeutic range. Using a hospital database, we compared AF patients ≥65 years who were bridged (n = 265) with patients who were not bridged (n = 4532) after hospital discharge. Patients who failed to achieve a therapeutic INR within 30 days were excluded. CHADS₂ scores (congestive heart failure, hypertension, age ≥75, diabetes, stroke), bleeding risk and co-morbidity scores were assessed. Unadjusted and adjusted odds ratios for outcome events (death, stroke, hemorrhage and venous thromboembolism (VTE) within 30 days of discharge were compared. Bridged patients, as compared to those not bridged, were younger (74.7 ± 6.6 vs. 78.5 ± 7.7 years), less likely to be white (36 vs. 51%), and less likely to have CHADS₂ scores ≥2 (67 vs. 84%), all P < 0.001. There was no significant difference in bleeding risk (bridged vs. not bridged: 1.5 ± 7 vs. 1.7 ± 6). In logistic models adjusting for age, white race, bleeding risk, CHADS₂ and Comorbidity scores, bridging was significantly associated with lower mortality and a decreased odds ratio for VTE (both P < 0.01) but not for stroke or hemorrhage (both P > 0.80). Although we found insufficient evidence of either lower stroke or greater bleeding risk with bridging, our data suggest the possibility that LMWH bridging in patients with AF is associated with lower risks of VTE and death within 30 days of discharge.     

Assessment of Small-Airways Disease Using Alveolar Nitric Oxide and Impulse Oscillometry in Asthma and COPD

The contribution of the alveolar compartment to exhaled nitric oxide (alveolar nitric oxide or CA_NO) can be calculated as a surrogate of distal inflammation. This value should be corrected for nitric oxide produced in the conducting airways which “back-diffuses” into the alveolar compartment (Corrected CA_NO). Impulse oscillometry (IOS) (Nava et al., Am J Respir Crit Care Med 168:1432–1437, 2003) is used to derive values for peripheral airways resistance. Twenty-four healthy volunteers, 21 severe asthmatics, 15 mild-to-moderate asthmatics, and 24 COPD patients were assessed with spirometry, impulse oscillometry, and fractionated exhaled nitric oxide. Compared to healthy volunteers, FE_NO was higher in mild-to-moderate and severe asthmatics: geometric mean fold ratios of 1.91 (P = 0.02) and 2.74 (P < 0.001), respectively. However, there was no difference for mild-to-moderate versus severe asthma. Ratios for CA_NO were not different for severe asthma versus COPD, but both were elevated compared to that of healthy volunteers [2.64 (P < 0.001) and 3.07 (P < 0.001), respectively] and mild-to-moderate asthma [1.95 (P = 0.04) and 2.28 (P < 0.01)]. However, after correction for axial diffusion, Corrected CA_NO was increased in COPD compared to severe asthma (geometric mean fold ratio 1.28, P = 0.04), mild-to-moderate asthma (1.34, P < 0.01), and healthy volunteers (1.28, P = 0.02), and there was no difference between other groups. R5 and RF were reduced in healthy volunteers versus mild-to-moderate asthma (P = 0.011 and P < 0.001 respectively), severe asthma (P = 0.002 and P < 0.001), and COPD (P < 0.001 and P < 0.001). Peripheral resistance (R5–R20) was not different for healthy versus mild-to-moderate asthma but was higher in severe asthma (P < 0.001) and COPD (P < 0.001). Correlations were observed between R5–R20 versus FEF_25–75 (r = 0.71, P < 0.01), CA_NO (r = 0.44, P < 0.01), and Corrected CA_NO (r = 0.24, P < 0.01). CA_NO and IOS provide additional information to traditional measures of spirometry and tidal nitric oxide. Previous data reporting elevated alveolar nitric oxide in severe asthma may reflect back-diffusion of nitric oxide from the conducting airways into the alveolar compartment. Corrected CA_NO and IOS may prove to be useful noninvasive measurements of small-airways disease.     

Treatment of obesity,with a dietary component,and eating disorder risk in children and adolescents: A systematic review with meta‐analysis

This review aimed to investigate the impact of obesity treatment, with a dietary component, on eating disorder (ED) prevalence, ED risk, and related symptoms in children and adolescents with overweight or obesity. Four databases were searched to identify pediatric obesity treatment interventions, with a dietary component, and validated pre‐post intervention assessment of related outcomes. Of 3078 articles screened, 36 met inclusion criteria, with a combined sample of 2589 participants aged 7.8 to 16.9 years. Intervention duration ranged from 1 week to 13 months, with follow‐up of 6 months to 6 years from baseline. Prevalence of ED was reported in five studies and was reduced post‐intervention. Meta‐analyses showed a reduction in bulimic symptoms (eight studies, standardized mean difference [SE], ?0.326 [0.09], P < 0.001), emotional eating (six studies, ?0.149 [0.06], P = 0.008), binge eating (three studies, ?0.588 [0.10], P < 0.001), and drive for thinness (three studies, ?0.167 [0.06], P = 0.005) post‐intervention. At follow‐up, a reduction in ED risk (six studies, ?0.313 [0.13], P = 0.012), emotional eating (five studies, ?0.259 [0.05], P < 0.001), eating concern (three studies, ?0.501 [0.06], P < 0.001), and drive for thinness (two studies, ?0.375 [0.07], P < 0.001) was found. Structured and professionally run obesity treatment was associated with reduced ED prevalence, ED risk, and symptoms.     

Impact of deprivation on cardiovascular risk factors in people with diabetes: an observational study

Aim To examine the influence of deprivation on prevalence of diabetes and of cardiovascular disease risk factors in people with diabetes. Methods Cross‐sectional study of 52 280 people in diabetes registers of Greater Glasgow and Lothian NHS Board areas linked to hospital admission data. Results Age‐ and sex‐adjusted prevalence of diabetes increased from 2.3% in the least deprived quintile (Q1) to 3.3% in the most deprived quintile (Q5; P < 0.001), as did prevalence of vascular disease (Q1 20%, Q5 27%; P < 0.001). Prevalence of current smoking (Q1 13%, Q5 32%; P < 0.001), obesity (Q1 38%, Q5 51%; P < 0.001) and above‐target glycated haemoglobin (HbA_1c; ≥ 7.5%: Q1 46% vs. Q5 47%; P = 0.01) were higher in the most deprived quintile. In contrast, the proportion of people with above‐target cholesterol were similar (proportion ≥ 5.0 mmol/l: Q1 26%, Q5 24%; P = 0.07) and the proportion of people with above‐target systolic blood pressure (SBP) was lower (SBP ≥ 140 mmHg: Q1 44%, Q5 37%; P = 0.02) in the most deprived quintile. In people with diabetes and prevalent vascular disease, deprivation was associated with failure to reach cholesterol target [odds ratio cholesterol ≥ 5.0 mmol/l: Q5 vs. Q1 1.23 (1.04–1.45) P = 0.013]. SBP and cholesterol were markedly lower compared with previous population surveys. Conclusions The burden of diabetes and vascular disease is greater in more deprived populations. Our data confirm a major advance in management of cholesterol and blood pressure management. Deprivation is still associated with failure to reach cholesterol targets in secondary prevention as well as higher prevalence of obesity and smoking.     

A multilocus genetic risk score predicts coronary heart disease risk in a Chinese Han population

Objective: Genome-wide association studies have identified multiple genetic loci associated with coronary heart disease (CHD) risk. However, whether these loci could improve the CHD risk prediction is unclear. Methods and results: The present case-control study (1146 CHD cases and 1146 controls) genotyped 19 recently discovered SNPs that associated with CHD risk. As a result, 10 SNPs were successfully replicated with odds ratios (ORs) ranging from 1.16 to 1.78 (P = 4.6 × 10⁻² to 5.99 × 10⁻⁶). A genetic risk score was constructed to assess the combined effects of the susceptibility loci on CHD risk. Subject in the second tertile (OR = 1.32, 95% CI, 1.02–1.73, P = 3.84 × 10⁻²) and the third tertile (OR = 2.62, 95% CI, 2.00–3.43, P = 3.18 × 10⁻¹²) had an increased risk of CHD comparing with those in the first genetic risk score tertile after adjustment for traditional risk factors including family history of CHD. Addition of the genetic risk score to the traditional model significantly improved the net reclassification as measured by the net reclassification index (NRI) (4.82%, P = 0.0001), however, no significant improvement was observed in discrimination of CHD, the area under the receiver operating characteristic curve (AUC) increased from 0.811 to 0.822 (P = 0.18). Conclusions: A multilocus genetic risk score was associated with CHD risk in a Chinese Han population. This genetic risk score improved the net reclassification but not improved the CHD discrimination. The potential clinical use of this variations remains to be defined.