The additional value of routine electrocardiograms in cardiovascular risk management of older people

Objective

To evaluate whether routinely performed ECGs in older people from the general population have added value for cardiovascular risk management beyond the information that is already available from their medical records

Design

Observational, prospective cohort study.

Setting

General population.

Subjects

A total of 566 participants aged 85 years (377 women, 189 men)

Methods

Lifelong history of cardiovascular disease was assessed through medical records obtained from general practitioners. Baseline ECGs were evaluated for prior myocardial infarction and atrial fibrillation. During a 5-year follow-up period, complete cardiovascular mortality and morbidity data were gathered

Results

During 5 years of follow-up, 262/566 (46%) participants died, of whom 102/262 (39%) died from cardiovascular disease. Participants with a history of cardiovascular disease at age 85 years (284/566, 50%) had an increased cardiovascular mortality (HR 2.7, 95% CI 1.8–4.1) and morbidity (HR _{myocardial infarction} 2.1, 95% CI 1.3–3.6; HR _stroke 2.7, 95% CI 1.6–4.9) compared with those without such a history. Participants with major ECG abnormalities (102/566, 18%) had an increased cardiovascular mortality (HR 1.8, 95% CI 1.1–2.8), but no increase of cardiovascular morbidity compared with those without major ECG abnormalities. In both participants with and without a history of cardiovascular disease, the presence of major ECG abnormalities was not associated with increased cardiovascular mortality or morbidity

Conclusions

In older people from the general population, a history of cardiovascular disease is a strong predictor of cardiovascular mortality and morbidity. Although abnormal findings on routine ECGs predict cardiovascular mortality, they do not provide additional prognostic information beyond the information available from medical records. Therefore, when accurate medical records are available, programmatic ECG recording is not effective in older people.     

Growth behavior of rat bone marrow cells on RF magnetron sputtered hydroxyapatite and dicalcium pyrophosphate coatings

The aim of this study was to evaluate the osteogenic properties of magnetron sputtered dicalcium pyrophaosphate (DCPP) and hydroxylapatite (HA) coatings. Therefore, DCPP and HA coatings were deposited on grit-blasted titanium discs. The substrates were used as-prepared or received an additional heat treatment which changed the amorphous coating structure to a crystalline structure. Subsequently, rat bone marrow stromal cells were cultured for 1-24 days on the various substrates. DNA and alkaline phosphatase activity was determined after 1, 3, 5, 8, and 12 days of incubation. Osteocalcin expression was evaluated after 8, 12, 16, and 24 days of incubation. Scanning electron microscopical analysis of cell morphology and coating characteristics was done after 8 and 16 days of incubation. All assays were done in duplicate and in each assay all specimens were present in fourfold. Results demonstrated that the cells did not proliferate and differentiate on all amorphous coatings. SEM revealed that the amorphous coatings showed significant dissolution. On the crystalline DCPP and HA coatings an increase in DNA and alkaline phosphatase activity was seen starting at day 8 of incubation. Osteocalcin expression on the crystalline coatings started to increase at day 16 of incubation. SEM showed that the growth and differentiation of the cells was associated with extensive collagen fiber formation and surface mineralization in the form of globular accretions. Further, statistical testing revealed that proliferation and differentiation of the rat bone marrow stromal cells started significantly earlier on the crystalline HA coatings than that on the crystalline DCPP coatings. These results demonstrate that the rat bone marrow stromal cells proliferated and differentiated only on crystalline magnetron sputtered DCPP as well as HA coatings, which warrants the further in vivo analysis of the bone healing supporting properties of these coatings.     

Viscoelastic properties of bovine articular cartilage attached to subchondral bone at high frequencies

Background  

Articular cartilage is a viscoelastic material, but its exact behaviour under the full range of physiological loading frequencies is unknown. The objective of this study was to measure the viscoelastic properties of bovine articular cartilage at loading frequencies of up to 92 Hz.     

Fever-induced QTc prolongation and ventricular arrhythmias in individuals with type 2 congenital long QT syndrome

Type 2 congenital long QT syndrome (LQT-2) is linked to mutations in the human ether a-go-go-related gene (HERG) and is characterized by rate-corrected QT interval (QTc) prolongation, ventricular arrhythmias, syncope, and sudden death. Recognized triggers of these cardiac events include emotional and acoustic stimuli. Here we investigated the repeated occurrence of fever-induced polymorphic ventricular tachycardia and ventricular fibrillation in 2 LQT-2 patients with A558P missense mutation in HERG. ECG analysis showed increased QTc with fever in both patients. WT, A558P, and WT+A558P HERG were expressed heterologously in HEK293 cells and were studied using biochemical and electrophysiological techniques. A558P proteins showed a trafficking-deficient phenotype. WT+A558P coexpression caused a dominant-negative effect, selectively accelerated the rate of channel inactivation, and reduced the temperature-dependent increase in the WT current. Thus, the WT+A558P current did not increase to the same extent as the WT current, leading to larger current density differences at higher temperatures. A similar temperature-dependent phenotype was seen for coexpression of the trafficking-deficient LQT-2 F640V mutation. We postulate that the weak increase in the HERG current density in WT-mutant coassembled channels contributes to the development of QTc prolongation and arrhythmias at febrile temperatures and suggest that fever is a potential trigger of life-threatening arrhythmias in LQT-2 patients.     

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutationsb

Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N‐acetylglucosamine‐6‐sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 in‐frame small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene. © 2010 Wiley‐Liss, Inc.     

Time trends in preventive drug treatment after myocardial infarction in older patients

Secondary preventive drug treatment in patients aged ≥60 years with a history of myocardial infarction was investigated for age-dependent differences in time trends. Sixteen general practices in the Netherlands participated. Preventive treatment with at least three of four drugs (antithrombotics, statins, beta-blockers, and/or angiotensin-converting enzyme inhibitors) increased significantly over time in all three age strata of older patients. Although the greatest relative increase (2.2 times greater) took place in patients aged ≥80 years, these patients consistently had most room for improvement.     

Phosphatidylcholine association increases the anti-inflammatory and analgesic activity of ibuprofen in acute and chronic rodent models of joint inflammation: relationship to alterations in bioavailability and cyclooxygenase-inhibitory potency.

We investigated whether chemical association of phosphatidylcholine (PC) to ibuprofen enhances the anti-inflammatory/analgesic activity of the nonsteroidal anti-inflammatory drug (NSAID) and whether any change in therapeutic action is due to alterations in drug bioavailability and cyclooxygenase (COX) inhibitory activity. Acute/chronic joint inflammation was induced in rats, by injection of Complete Freund's Adjuvant. In the acute study, rats were administered saline, ibuprofen, or PC-ibuprofen (at NSAID doses of 10, 25, and 50 mg/kg), and 2 h later the pain threshold of the affected joint to pressure was measured. PC-ibuprofen increased the pain threshold at all NSAID doses, whereas unmodified ibuprofen demonstrated analgesic activity at only the highest dose. In the chronic study, we investigated the effects of saline, PC-ibuprofen, and ibuprofen (administered at 15 and 25 mg/kg/day) on ankle thickness and pain threshold, and demonstrated that PC-ibuprofen had significantly greater anti-inflammatory and analgesic activity than ibuprofen, over a 30- to 60-day period. PC association resulted in reduced uptake (decreased Cmax), a modest increase in the area under the curve, and a longer t(1/2) of ibuprofen. We also demonstrated that PC-ibuprofen was a comparable or a more effective inhibitor of both 6-keto-prostaglandin F1alpha concentration of fluid collected from tissue in and around the inflamed stifle joint, and COX-2 activity in activated human umbilical vein endothelial cells. In conclusion, we have demonstrated that PC association results in increases in ibuprofen's anti-inflammatory and analgesic activity in rodent models of acute and chronic joint inflammation, and this effect may relate to alterations in drug bioavailability and COX-inhibitory potency.     

When "no" might not quite mean "no"; the importance of informed and meaningful non-consent: results from a survey of individuals refusing participation in a health-related research project

Background  

Low participation rates can lead to sampling bias, delays in completion and increased costs. Strategies to improve participation rates should address reasons for non-participation. However, most empirical research has focused on participants' motives rather than the reasons why non-participants refuse to take part. In this study we investigated the reasons why older people choose not to participate in a research project.