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Aging is associated with hepatic growth hormone resistance resulting in a fall in serum insulin-like growth factor 1 (IGF-1) level. However, whether loss of IGF-1 contributes to cardiac aging is unclear. This study was designed to examine the effect of cardiac overexpression of IGF-1 on cardiomyocyte contractile function in young (3 mo) and old (26-28 mo) mice. Cardiomyocyte contractile function was evaluated, including peak shortening (PS), time to 90% PS, time to 90% relengthening (T[R.sub.90]), and maximal velocity of shortening/relengthening ([+ or -] dL/dt). Levels of advanced glycation end product, protein carbonyl, sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase (SERCA2a), phospholamban, and [Na.sup.+]/[Ca.sup.2+] exchanger were assessed by Western blot analysis. SERCA activity was measured by [sup.45][Ca.sup.2+] uptake. Aging induced a decline in plasma IGF-1 levels. Aged cells exhibited depressed [+ or -] dL/dt, prolonged T[R.sub.90], and a steeper PS decline in response to increasing stimulus frequency compared with those in young myocytes. IGF-1 transgene alleviated aging-induced loss in plasma IGF-1 and aging-induced mechanical defects with little effect in young mice. The beneficial effect of IGF-1 transgene on aging-associated cardiomyocyte contractile dysfunction was somewhat mimicked by short-term in vitro treatment of recombinant IGF-1 (500 nM). Advanced glycation end product and protein carbonyl levels were higher in aged mice, which were not affected by IGF-1. Expression of SERCA2a (but not [Na.sup.+]/[Ca.sup.2+] exchanger and phospholamban) and SERCA activity were reduced with aging, which was ablated by the IGF-1 transgene. Collectively, our data suggest a beneficial role of IGF-1 in aging-induced cardiac contractile dysfunction, possibly related to improved [Ca.sup.2+] uptake. cardiomyocytes; contractile function; calcium regulatory protein; senescence

The article presents a study that examined the association between atrial fibrillation (AF) and increased risk of sudden cardiac death (SCD).The study reveals the link between incident AF and increased risk of SCD and non-SCD in the general population. It proposes additional research to identify predictors of SCD in patients with AF.

Aging is associated with hepatic growth hormone resistance resulting in a fall in serum insulin- like growth factor I (IGF-l) level. However, whether loss of IGF-l contributes to cardiac aging is unclear. This study was designed to examine the effect of cardiac overexpression of IOF-1 on cardiomy- ocyte contractile function in young (3 mo) and old (26-28 mo) mice. Cardiomyocyte contractile function was evaluated, including peak shortening (PS), time to 90% PS, time to 90% relengthening (TR90), and maximal velocity of shortening/relengthening (±dL/dt). Levels of advanced glycation end product, protein carbonyl, sarco(endo)plasmic reticulum Ca2~-ATPase (SERCA2a), phospholamban, and Na~ICa2~ exchanger were assessed by Western blot analysis. SERCA activity was measured by 45Ca2~ uptake. Aging induced a decline in plasma IGF- 1 levels. Aged cells exhibited depressed ±dL/dt, prolonged TR90, and a steeper PS decline in response to increasing stimulus frequency compared with those in young myocytes. IGF-I transgene alleviated aging-induced loss in plasma IGF- I and aging-induced mechanical defects with little effect in young mice. The beneficial effect of IGF- I transgene on aging-associated cardiomyocyte contractile dysfunction was somewhat mimicked by short-term in vitro treatment of recom- binant IGF-1 (500 nM). Advanced glycation end product and protein carbonyl levels were higher in aged mice, which were not affected by IF-I. Expression of SERCA2a (but not Na~ICa2~ exchanger and phospholamban) and SERCA activity were reduced with aging, which was ablated by the IF-I transgene. Collectively, our data suggest a beneficial role of IGF- 1 in aging-induced cardiac contractile dysfunc- tion, possibly related to improved Ca2~ uptake. [ABSTRACT FROM AUTHOR]

Background: Little attention has been devoted to the timing of risk factor development in relation to atrial fibrillation (AF) diagnosis. We assessed the long term trajectories of risk factors and cardiovascular (CV) outcomes in the Atherosclerosis Risk in Communities (ARIC) study, a US community-based cohort. Methods: Our analysis included 2134 individuals with incident AF and 5674 controls matched with cases 1:3 on age, sex, race and center, participating in the ARIC study. Information on incident AF and risk factors / CV outcomes (obesity, hypertension, smoking, diabetes, heart failure (HF), myocardial infarction (MI), and stroke) was obtained during 5 study exams between 1987 and 2013, and surveillance of CV events through 2010. The prevalence of risk factors / CV outcomes in the period before and after the diagnosis of AF (and the corresponding index date for controls) was modeled using general estimating equations models. Adjusted odds ratios (OR) of risk factors / CV outcomes were calculated, using the index date ±2.5 years as the reference group. The interaction of time with AF was used to compare differences in trajectories. Results: During a median follow-up of 24 years, we observed diverse trajectories in the prevalence of risk factors and CV outcomes among AF patients, with steep increases in the prevalence of stroke, MI and HF during the period close to AF diagnosis, while trajectories for hypertension and diabetes showed monotonic increases, and those for smoking and obesity suggested decreases in prevalence after AF diagnosis (Figure A). The trajectories over time for hypertension, obesity, HF, stroke and MI were significantly different based on AF status, with lower increments among those without AF (Figure A and B). Conclusion: In this large population-based study, trajectories in the odds of risk factors and CV outcomes were diverse, suggesting they could have different roles in the pathogenesis of AF. The prevalence of CV outcomes increased after AF diagnosis, and trajectories differed by AF status. [ABSTRACT FROM AUTHOR]