Multilevel analysis of systolic blood pressure and ACE gene I/D polymorphism in 438 Swedish families – a public health perspective

BACKGROUND: Individuals belonging to the same family share a number of genetic as well as environmental circumstances that may condition a common SBP level. Among the genetic factors, the angiotensin converting enzyme (ACE) gene I/D polymorphism appears as a possible candidate as it might influence both SBP and the pharmacological effect of ACE inhibitors. We aimed to combine genetic epidemiology with public health ideas concerning life-course and multilevel epidemiology in order to understand the role of familial factors regarding individual SBP. METHODS: We applied multilevel regression analysis on 1926 individuals nested within 438 families from South Sweden. Modelling familial SBP variance as a function of age and use of ACE inhibitors we calculates a variance partition coefficient and the proportional change in familial SBP variance attributable to differences in ACE gene I/D polymorphism RESULTS: Our results suggest the existence of genetic or environmental circumstances that produce a considerable familial clustering of SBP, especially among individuals using ACE-inhibitors. However, ACE gene I/D polymorphism seems to play a minor role in this context. In addition, familial factors – genetic, environmental or their interaction – shape SBP among non-users of ACE inhibitors but their effect is expressed later in the life-course. CONCLUSION: Strategies directed to prevent hypertension should be launched in younger rather than in older ages and both prevention of hypertension and its treatment with ACE inhibitors should be focused on families rather than on individuals

Antihypertensive medication prescription patterns and time trends for newly-diagnosed uncomplicated hypertension patients in Taiwan

<p>Abstract</p> <p>Background</p> <p>Knowledge of existing prescription patterns in the treatment of newly-diagnosed hypertension can provide useful information for improving clinical practice in this field. The aims of this study are to determine the prescription patterns and time trends for antihypertensive medication in newly-diagnosed cases of uncomplicated hypertension in Taiwan and to compare these with current clinical guidelines.</p> <p>Methods</p> <p>A total of 6,536 newly-diagnosed patients with uncomplicated hypertension, aged ≥30 years, were identified from the representative 200,000-person sample in the computerized reimbursement database of the National Health Insurance in Taiwan. These patients were followed from 1998 to 2004 with all diagnoses, prescription data and medication charges being retrieved for subsequent analysis.</p> <p>Results</p> <p>Prescription patterns varied by age, gender and clinical facilities, with mono-therapies being found to be dominant in the first year, albeit declining over time. Calcium channel blockers and beta-blockers were the most frequently prescribed antihypertensive drugs, either alone or in combinations. Although least expensive, the prescription rates of diuretics were low, at 8.3% for mono-therapies and 19.9% overall. The prescription rate for angiotensin receptor blockers (ARBs) was elevated considerably over time. After controlling for other related factors by multiple logistic regression analysis, ARBs were found to be prescribed mainly by medical centers or regional hospitals.</p> <p>Conclusion</p> <p>These findings indicate the existence of a gap between current clinical practice and the desired goal of cost-effectiveness in antihypertensive treatment in Taiwan, which should be corrected.</p

Transferrin changes in haemodialysed patients

Transferrin (Tf) is a glycoprotein responsible for iron transport in the human body. Physiologically in reaction with Concanavalin A, Tf occurs in four distinct variants Tf1, Tf2, Tf3 (apo-Tf) and Tf4. It was reported recently that Tf is changing, particularly during acute phase response, taking place among others in end-stage renal disease. In this study, we wanted to find the answer to three main questions: firstly, how Tf is changing in patients treated with maintenance haemodialysis (mHD), secondly, whether there are any Tf changes in the course of mHD treatment, and thirdly, what factors can affect Tf microheterogeneity in these patients. Studies were performed on 80 haemodialysed patients and 21 healthy volunteers. The Tf concentration was determined by the rocket immunoelectrophoresis, and its microheterogeneity was assessed by the ConA crossed immunoaffinity electrophoresis. During the annual observation of the distribution of the Tf variants, we have found both changes of the percentage contents of all Tf variants in the whole Tf concentration and a significant decrease in Tf2, Tf3 and Tf4 serum concentrations. Moreover, we found that decrease in the renal function, duration of mHD, and inflammation may contribute to these above-mentioned changes, which are probably the factors that should be taken into account when explaining the mechanisms of persistence of anaemia in haemodialysed patients

The Asp298 allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus

Background: Endothelial dysfunction plays a central role in atherosclerotic progression and cardiovascular complications of type 2 diabetes mellitus (T2DM). Given the role of nitric oxide in the vascular system, we aimed to test hypotheses of synergy between the common endothelial nitric oxide synthase (eNOS) Asp(298) allele and T2DM in predisposing to acute myocardial infarction (AMI). Methods: In a population-based patient survey with 403 persons with T2DM and 799 healthy subjects from the population without diabetes or hypertension, we analysed the relation between T2DM, sex and the eNOS Asp(298) allele versus the risk for AMI. Results: In an overall analysis, T2DM was a significant independent risk factor for AMI. In patients with T2DM, homozygosity for the eNOS Asp(298) allele was a significant risk factor (HR 3.12 [1.49-6.56], p = 0.003), but not in subjects without diabetes or hypertension. Compared to wild-type non-diabetic subjects, all patients with T2DM had a significantly increased risk of AMI regardless of genotype. This risk was however markedly higher in patients with T2DM homozygous for the Asp(298) allele (HR 7.20 [3.01-17.20], p < 0.001), independent of sex, BMI, systolic blood pressure, serum triglycerides, HDL -cholesterol, current smoking, and leisure time physical activity. The pattern seemed stronger in women than in men. Conclusion: We show here a strong independent association between eNOS genotype and AMI in patients with T2DM. This suggests a synergistic effect of the eNOS Asp(298) allele and diabetes, and confirms the role of eNOS as an important pathological bottleneck for cardiovascular disease in patients with T2DM

The Ontario printed educational message (OPEM) trial to narrow the evidence-practice gap with respect to prescribing practices of general and family physicians: a cluster randomized controlled trial, targeting the care of individuals with diabetes and hypertension in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>There are gaps between what family practitioners do in clinical practice and the evidence-based ideal. The most commonly used strategy to narrow these gaps is the printed educational message (PEM); however, the attributes of successful printed educational messages and their overall effectiveness in changing physician practice are not clear. The current endeavor aims to determine whether such messages change prescribing quality in primary care practice, and whether these effects differ with the format of the message.</p> <p>Methods/design</p> <p>The design is a large, simple, factorial, unblinded cluster-randomized controlled trial. PEMs will be distributed with <b><it>informed</it></b>, a quarterly evidence-based synopsis of current clinical information produced by the Institute for Clinical Evaluative Sciences, Toronto, Canada, and will be sent to all eligible general and family practitioners in Ontario. There will be three replicates of the trial, with three different educational messages, each aimed at narrowing a specific evidence-practice gap as follows: 1) angiotensin-converting enzyme inhibitors, hypertension treatment, and cholesterol lowering agents for diabetes; 2) retinal screening for diabetes; and 3) diuretics for hypertension.</p> <p>For each of the three replicates there will be three intervention groups. The first group will receive <b><it>informed </it></b>with an attached postcard-sized, short, directive "outsert." The second intervention group will receive <b><it>informed </it></b>with a two-page explanatory "insert" on the same topic. The third intervention group will receive <b><it>informed</it></b>, with both the above-mentioned outsert and insert. The control group will receive <b><it>informed </it></b>only, without either an outsert or insert.</p> <p>Routinely collected physician billing, prescription, and hospital data found in Ontario's administrative databases will be used to monitor pre-defined prescribing changes relevant and specific to each replicate, following delivery of the educational messages. Multi-level modeling will be used to study patterns in physician-prescribing quality over four quarters, before and after each of the three interventions. Subgroup analyses will be performed to assess the association between the characteristics of the physician's place of practice and target behaviours.</p> <p>A further analysis of the immediate and delayed impacts of the PEMs will be performed using time-series analysis and interventional, auto-regressive, integrated moving average modeling.</p> <p>Trial registration number</p> <p>Current controlled trial ISRCTN72772651.</p

Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project

Aims The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K-ATP-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. Methods A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. Results Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). Conclusions We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors