Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

OBJECTIVE: Based on case-control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke. DESIGN: A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. SETTING: Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. MAIN OUTCOME MEASURES: CVD mortality event. RESULTS: The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02-3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen. CONCLUSION: We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD.     

Five-year trend in serum HDL-lipoprotein cholesterol in the Finnish population aged 25-64 years. A suggestion of an increase

High density lipoprotein cholesterol (HDLC) was measured in the population surveys carried out in Finland in 1982 and 1987. The mean (+/- SD) of HDLC for men aged 25-64 years was 1.23 +/- 0.32 mmol/l in 1982 and 1.30 +/- 0.33 mmol/l in 1987, the increase being 5.7%. Respective values in women were 1.46 +/- 0.33 mmol/l and 1.58 +/- 0.35 mmol/l, an increase of 8.2%. The increase was significantly greater in women than in men (P less than 0.001). The prevalence of low HDLC (less than or equal to 0.9 mmol/l) fell from 13.5 to 9.6% in men and from 3.2 to 1.4% in women. Factors associated with low HDLC were the history of ischemic heart disease (IHD), diabetes and hypertension in both sexes and the positive family history of IHD in women. Subjects with low HDLC also had higher body mass index (BMI), waist-hip ratio and serum total cholesterol (TC) concentration than subjects with normal HDLC. Changes in BMI, waist-hip ratio, alcohol intake, leisure time physical activity, prevalence of smoking or in the dietary variables recorded, did not explain the increase in HDLC.     

Laminin isoforms in fetal and adult human adrenal cortex

Laminin has been proposed to influence the function of human adrenal cortex. We have studied the distribution of laminin (Ln) chains using immunofluorescence in human fetal and adult adrenal cortex. In the fetal gland Ln alpha2- and alpha5-chains were weakly expressed in the definitive zone, whereas Ln alpha4-, beta1-, and gamma1-chains occurred around vessels. In the adult gland, Ln alpha2-, alpha5-, and gamma1-chains were found in epithelial basement membranes (BM) in all cortical zones, Ln alpha4-chain in vessels, Ln beta1-chain in outer zone, and Ln beta2-chain in the two inner zones of the cortex, respectively. Among the integrins in adult gland, integrin alpha(3)-subunit was confined to basal surfaces of cortical cells, alpha(6) to vessels, alpha(1) to the stroma, and alpha(2) diffusely to epithelial cells. Lutheran glycoprotein and dystroglycan occurred in the fetal gland diffusely in the definitive zone and throughout the epithelium in the adult. The isoform composition of BM of the adult adrenal gland is distinct, with Ln-2 and -10 in BM of the outer zone and Ln-4 and -11 in BM of the two inner zones. The results suggest that integrin alpha(3)beta(1) and Lutheran are candidate receptors for Ln-10 and -11, whereas dystroglycan probably binds Ln-2 and -4.     

Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents

This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer's disease (AD). Forty-seven 40–80-year-old NL received positron emission tomography (PET) with ¹¹C-Pittsburgh compound B (PiB) and 18F-fluoro-2-deoxy-d-glucose (FDG). These included 19 NL with a maternal history (MH), 12 NL with a paternal history (PH), and 16 NL with negative family history of AD (NH). Automated regions of interest, statistical parametric mapping, voxel-wise intermodality correlations, and logistic regressions were used to examine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios across groups. The MH group showed higher PiB retention and lower metabolism in AD regions compared with NH and PH, which were negatively correlated in posterior cingulate, frontal, and parieto-temporal regions (Pearson r ≤ −0.57, p ≤ 0.05). No correlations were observed in NH and PH. The combination of Aβ deposition and metabolism yielded accuracy ≥ 69% for MH vs. NH and ≥ 71% for MH vs. PH, with relative risk = 1.9–5.1 (p values < 0.005). NL individuals with AD-affected mothers show co-occurring Aβ increases and hypometabolism in AD-vulnerable regions, suggesting an increased risk for AD.     

Pharmacokinetics of digoxin in patients with acute myocardial infarction.

The effects of acute myocardial infarction on the pharmacokinetics of digoxin were studied. Digoxin, 0.75 mg, was given orally to 12 patients with left-sided cardiac failure due to acute myocardial infarction and to 9 healthy control subjects. Serum concentration of digoxin in the first 4 hours and the area under the serum concentration-time curve in the first 12 hours after administration of the drug were lower in patients with infarction than in control subjects (P less than 0.01). The 24 hour area under the concentration curve, the amount excreted in urine and the renal clearance did not differ between the groups. The 24 hour area under the concentration curve correlated with the predigoxin pulmonary capillary wedge pressure and with heart rate (P less than 0.01). The decrease of renal clearance of digoxin was related to the serum activity of MB isoenzyme of creatine kinase (P less than 0.001). Morphine reduced and delayed the peak serum concentrations of digoxin (P less than 0.001). Thus, the absorption of oral digoxin was slower and the peak concentrations remained lower in patients with acute myocardial infarction than in healthy control subjects. However, the total amount of digoxin absorbed was unchanged.     

Physicians’ views on patient participation in choice of oral anticoagulants in atrial fibrillation—a qualitative study

Direct oral anticoagulants provide an alternative to vitamin K antagonists for the anticoagulation therapy in atrial fibrillation (AF). The availability of several treatment options with different attributes makes shared decision‐making appropriate for the choice of anticoagulation therapy. The aim of this study was to understand how physicians choose an oral anticoagulant (OAC) for patients with AF and how physicians view patients’ participation in this decision. Semi‐structured interviews with 17 Finnish physicians (eight general practitioners and nine specialists) working in the public sector were conducted. An interview guide on experience, prescribing and opinions about oral anticoagulants was developed based on previous literature. The data were thematically analysed using deductive and inductive approaches. Based on the interviews, patient's opinion was the most influential factor in decision‐making when there were no clinical factors limiting the choice between OACs. Of patient's preferences, the most important was the attitude towards co‐payments of OACs. Patients’ opinions on monitoring of treatment, dosing and antidote availability were also mentioned by the interviewees. The choice of an OAC in AF was patient‐centred as all interviewees expressed that patient's opinion affects the choice.