C-Reactive Protein Levels and the Risk of Incident Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.

PURPOSE: Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular and cerebrovascular disease (CVD) but it is unclear who are at greatest risk. We determined whether the inflammatory marker, C-reactive protein (CRP), could be a useful prognostic biomarker. METHODS: Adult patients referred for polysomnography (PSG) with OSA were studied. Serum CRP levels were measured using ELISA the morning after PSG. Validated CV events within 4 years of PSG were ascertained by linking to provincial research datasets. RESULTS: 155 patients with OSA (AHI ≥ 5/h) had CRP measured. Median age was 53 and median AHI was 21/h. 10 patients (7.1%) suffered at least one event, but rates varied substantially by CRP (0/35 patients in the lowest quartile, and 7/39 in the highest CRP quartile). In the unadjusted analysis, patients in the highest CRP quartile (≥ 2.38 mg/L) were significantly more likely to suffer an event (odds ratio = 9.72 (95% CI 2.43-38.84), p = 0.001). CRP continued to be a significant predictor after controlling for multiple confounders. OSA severity and desaturation were not significantly associated with prospective events. CONCLUSIONS: In this small preliminary study, OSA patients with an elevated CRP were significantly more likely to suffer a CVD event in the 4 years after PSG. Although these findings need to be confirmed in larger prospective cohorts, CRP may be useful in risk stratifying OSA patients to guide therapy or to identify patients that might be most appropriate for clinical trials of CVD prevention.

Percentile distribution of blood pressure readings in 35683 men and women aged 18 to 99 years.

The percentile distribution of blood pressure (BP) with regard to age, sex and cardiovascular risk factors is unknown. We aimed to provide epidemiological data for a comprehensive description of the BP distribution across a wide age-range. We used data from the German Metabolic and Cardiovascular Risk Project (GEMCAS), a cross-sectional study with 35 683 participants aged 18-99 years, conducted during October 2005 in 1511 randomly selected general practices in Germany. BP and waist circumference were measured, data on lifestyle, cardiovascular disease (CVD) risk factors and medication assessed. In men, we found even in the lowest percentile (5th) a gradual increase of the systolic BP from the lowest to the highest age group of 10 mm Hg, all other percentile groups an increase of 20 mm Hg. In women, this increase ranged from 15 mm Hg (5th percentile) to 40 mm Hg (95th percentile). In a subgroup of participants with no antihypertensive usage (n=22 550) and no CVD/CVD risk factors (n=13 297), we still observed a distinct age-related increase of BP readings. Our study provides detailed information on the population distribution of BP readings in both sexes and also among very old individuals. The results are useful in a public health context to plan gender- and age-specific prevention strategies.

Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin.

Statins are generally well tolerated, but can cause myopathy and have been associated with mitochondrial abnormalities. The aim of this study was to determine whether muscle mitochondrial DNA (mtDNA) levels are altered during statin therapy. We retrospectively quantified mtDNA in 86 skeletal muscle biopsy specimens collected as part of a previously published clinical trial of high-dose simvastatin or atorvastatin versus placebo.

Parity and carotid artery atherosclerosis in elderly women: The Rotterdam Study.

BACKGROUND AND PURPOSE: It has been postulated that physiological changes in the cardiovascular system, lipids, and glucose metabolism during pregnancy may increase subsequent risk of cardiovascular disease. Examination of the association between parity and risk factors for atherosclerosis may contribute information regarding possible mechanisms. METHODS: The relationship of parity with cardiovascular risk factors and the presence of carotid atherosclerosis was examined in the Rotterdam Study, a population-based study comprising 4878 women aged 55 years and older. Carotid atherosclerosis was assessed by ultrasonographic detection of plaques in the common carotid artery and bifurcation. Logistic regression models were used to compute odds ratios and 95% confidence intervals, adjusted for confounding factors. RESULTS: Parity was inversely associated with high-density lipoprotein cholesterol, and alcohol intake. Parity was positively associated with body mass index, total/HDL cholesterol ratio, insulin resistance, age at menopause, and socioeconomic status. Relative to nulliparous women, parous women had 36% (9% to 71%) greater risk of carotid atherosclerosis, rising to 64% in women with >/=4 children (19% to 127%). Adjustment for known cardiovascular risk factors, including insulin resistance and current lipid levels, did not diminish the magnitude of this association. CONCLUSIONS: Data demonstrated that there is a positive association between parity and risk of carotid artery plaques in elderly women and, further, that high parity is associated with lower HDL cholesterol levels and higher glucose/insulin ratios long after childbearing has ceased.

New-onset atrial fibrillation: sex differences in presentation, treatment, and outcome.

BACKGROUND: Although sex differences in coronary artery disease have received considerable attention, few studies have dealt with sex differences in the most common sustained cardiac arrhythmia, atrial fibrillation (AF). Differences in presentation and clinical course may dictate different approaches to detection and management. We sought to examine sex-related differences in presentation, treatment, and outcome in patients presenting with new-onset AF. METHODS AND RESULTS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled subjects at the time of first ECG-confirmed diagnosis of AF. Participants were followed at 3 months, at 1 year, and annually thereafter. Treatment was at the discretion of the patients' physicians and was not directed by CARAF investigators. Baseline and follow-up data collection included a detailed medical history, clinical, ECG, and echocardiographic measures, medication history, and therapeutic interventions. Three hundred thirty-nine women and 560 men were followed for 4.14+/-1.39 years. Compared with men, women were older at the time of presentation, more likely to seek medical advice because of symptoms, and experienced significantly higher heart rates during AF. Compared with older men, older women were half as likely to receive warfarin and twice as likely to receive acetylsalicylic acid. Compared with men on warfarin, women on warfarin were 3.35 times more likely to experience a major bleed. CONCLUSIONS: Anticoagulants are underused in older women with AF relative to older men with AF, despite comparable risk profiles. Women receiving warfarin have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.

Co-morbidity data in outcomes research: are clinical data derived from administrative databases a reliable alternative to chart review?

Evaluation of co-morbidity data is essential in health outcomes research. Co-morbidity data derived from administrative databases has been criticized for lacking the accuracy required for clinical research. We compared co-morbidity data derived from a Canadian provincial hospitalization database with chart review in 817 adults treated with a percutaneous coronary intervention at a single tertiary care hospital between 1994 and 1995. While the administrative database tended to under-estimate the prevalence of some co-morbid conditions, the agreement between chart review and administrative data was good to very good for most conditions. Asymptomatic conditions were noted to have lower levels of agreement. Multivariate risk models for all-cause mortality constructed from both data sources were almost identical, suggesting minimal misclassification. The results indicate that clinical data abstracted from most Canadian hospitalization databases can provide reliable information regarding baseline co-morbid conditions believed to influence survival in a population undergoing percutaneous coronary interventions.

Income-related health inequality in Canada.

This study uses data from the 1994 National Population Health Survey and applies the methods developed by Wagstaff and van Doorslaer (1994, measuring inequalities in health in the presence of multiple-category morbidity indicators. Health Economics 3, 281-291) to measure the degree of income-related inequality in self-reported health in Canada by means of concentration indices. It finds that significant inequalities in self-reported ill-health exist and favour the higher income groups--the higher the level of income, the better the level of self-assessed health. The analysis also indicates that lower income individuals are somewhat more likely to report their self-assessed health as poor or less-than-good than higher income groups, at the same level of a more 'objective' health indictor such as the McMaster Health Utility Index. The degree of inequality in 'subjective' health is slightly higher than in 'objective' health, but not significantly different. The degree of inequality in self-assessed health in Canada was found to be significantly higher than that reported by van Doorslaer et al. (1997, income related inequalities in health: some international comparisons, Journal of Health Economics 16, 93-112) for seven European countries, but not significantly different from the health inequality measured for the UK or the US. It also appears as if Canada's health inequality is higher than what would be expected on the basis of its income inequality.

Digoxin-like immunoreactivity, displacement of ouabain and inhibition of Na+/K+ ATPase by four steroids known to be increased in essential hypertension.

An endogenous digoxin-like immunoreactive substance(s) (DLIS, "endoxin") may be of significance in the etiology of essential hypertension (EH). Progesterone, dehydroepiandrosterone sulphate (DHEA-S), 11-deoxycortisol and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), four steroids known to be increased in essential hypertension, were found to have digoxin-like immunoreactivity at levels 1,000 times higher than physiological concentrations. Of these steroids, progesterone and 18-OH-DOC were the most efficient in displacing 3H-ouabain from canine kidney Na+/K+ ATPase whereas progesterone and 11-deoxycortisol were the most potent inhibitors of this enzyme's activity. Although 18-OH-DOC and DHEA-S cross-reacted with digoxin-specific antibodies, their ability to inhibit Na+/K+ ATPase activity was minimal. Although it is concluded that these steroids may contribute to DLIS as isolated from hypertensive patients, it is unlikely that they would be of physiological significance in the etiology of EH unless they were to accumulate and act synergistically within vascular wall smooth muscle tissues.

A study into the nature and organ source of digoxin-like immunoreactive substance(s) in the perinatal period.

Digoxin-like immunoreactive substance(s) (DLIS) was isolated from sera and autopsy-derived tissue obtained from premature and full-term neonates. The highest tissue level of DLIS was in the small bowel followed by the adrenal, gallbladder and liver. Of the fluids examined, meconium had the highest level of DLIS. Preparative high performance liquid chromatography fractionation of cord blood generated at least six different fractions which not only contained DLIS material but also inhibited canine kidney Na+/K+-ATPase activity. Recovery/inhibition studies indicated that 72% of the canine kidney Na+/K+-ATPase inhibition within one fraction could be accounted for on the basis of progesterone content of the fraction.

Minimizing analytical interferences from digoxin-like immunoreactive substances (DLIS) in cases of digoxin toxicity.

Recently, the value of therapeutic drug monitoring for digoxin has been called into question by the finding of endogenous digoxin-like immunoreactive substances (DLIS) in the serum of individuals, especially premature and full-term neonates, not being treated with digoxin. In some cases, values have been as high as 10 micrograms/L. Levels as high as 20 micrograms/L and 80 micrograms/g can be found in bile and meconium. Because of the magnitude of this interference, it is essential that methods be developed for measuring digoxin in the presence of DLIS. This is particularly important when such analyses are required in forensic science cases of suspected digoxin toxicity. This report outlines the high performance liquid chromatographic (HPLC) and radioimmunoassay (RIA) methods that we used in assessing the relative contribution made by digoxin, its metabolites, and DLIS to serum and tissue digoxin concentrations obtained by RIA in a forensic pediatric case of suspected digoxin toxicity.