Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone

OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF).

BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown.

METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained.

RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide.

CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).

The impact of childhood residential mobility on mental health outcomes in adolescence and early adulthood: a record linkage study.

Background Understanding the causes of poor mental health in early childhood and adolescence is important as this can be a significant determinant of mental well-being in later years. One potential and relatively unexplored factor is residential mobility in formative years. Previous studies have been relatively small and potentially limited due to methodological issues. The main aim of this study was to investigate the relationship between early residential instability and poor mental health among adolescents and young adults in Northern Ireland.

Methods A Census-based record linkage study of 28% of children aged 0–8 years in 2001 in Northern Ireland (n=49 762) was conducted, with six monthly address change assessments from health registration data and self-reported mental health status from the 2011 Census. Logistic regression models were built adjusting for socioeconomic status (SES), household composition and marital dissolution.

Results There was a graded relationship between the number of address changes and mental ill-health (adjusted OR 3.67, 95% CIs 2.11 to 6.39 for 5 or more moves). This relationship was not modified by SES or household composition. Marital dissolution was associated with poor mental health but did not modify the relationship between address change and mental health (p=0.206). There was some indication that movement after the age of five was associated with an increased likelihood of poor mental health.

Conclusions This large study clearly confirms the close relationship between address change in early years and later poor mental health. Residential mobility may be a useful marker for children at risk of poorer mental health in adolescence and early adulthood

Welcome to the Occupation: Patterns in the Management of the Fourteenth-Century English Landscape

Occupation of the landscape took many different forms and is one of the predominant ways of viewing settlement within the medieval world. Buildings are the most effective method of occupying space, both physically and psychologically. This paper will draw on current research into fourteenth century manorial buildings in England and explore how they were used to occupy both the landscape and the communities associated with them.