High blood hemoglobin concentration as risk factor of major atherosclerotic cardiovascular events in 114,159 healthy men and women in the apolipoprotein mortality risk study (AMORIS).
ABSTRACT Few studies have tested differences in relationships between hemoglobin (Hb) and long-term risk of major cardiovascular diseases according to age and gender in healthy subjects as opposed to anemia.
Such relationships were examined and risk-tested in relation to Hb values in the Apolipoprotein MOrtality RISk (AMORIS) Study.
Using data from AMORIS and the Swedish hospital discharge and mortality registers, a prospective cohort study of 114,159 subjects with mean follow-up of 11.8 years, the association between Hb and risk of acute myocardial infarction (AMI), ischemic stroke (IS), and congestive heart failure (CHF) by Cox regression analysis according to age and gender was studied.
Elevated Hb levels were associated to acute myocardial infarction (AMI) (HR 1.10 (1.06-1.13) per SD change), mostly confined to men and younger subjects but with greater sex similarity trends for CHF. Slightly increased risks were seen for the lowest Hb levels in the elderly and in females. IS risk was positively and more linearly associated to Hb.
In AMORIS the highest AMI and CHF risks were found in the upper region of the distribution, but different shapes of relationships according to age and gender were found. IS associated positively with Hb. Key words:
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Impaired renal function and anaemia are common among patients with acute myocardial infarction (AMI). While both conditions are known independent risk factors for increased mortality, their interaction as risk factors for increased mortality in AMI is unclear. METHODS: We studied 5395 subjects hospitalized for AMI between January 2000 and December 2005. An estimated glomerular filtration rate (GFR) <60mL/min/1.73m(2) was defined as impaired GFR and GFR ≥60mL/min/1.73m(2) was defined as preserved GFR. Anaemia was defined as <13g/dL (males) and <12g/dL (females). The odds ratio (OR) for one-year mortality and its 95% confidence interval (CI) were calculated by logistic regression. RESULTS: We identified 758 (14%) patients with impaired GFR and anaemia, 1105 (20.5%) patients with impaired GFR without anaemia, 465 (8.6%) patients with preserved GFR and anaemia, and 3012 (55.8%) patients with preserved GFR without anaemia; one-year mortality rates were 56.5%, 41.8%, 31.8% and 10.3% respectively in these 4 groups. Among patients with impaired GFR, anaemia was associated with an adjusted OR of 1.47 (95% CI=1.17-1.85) for one-year mortality, while among patients with preserved GFR, anaemia was associated with a higher adjusted OR of 2.07 (95% CI=1.54-2.76) for one-year mortality, interaction P<0.001. CONCLUSION: The combination of impaired GFR and anaemia confers greater than five-fold increased risk of mortality after AMI. The differential effect of anaemia among patients with impaired and preserved GFR on mortality suggests that in patients with preserved GFR anaemia confers a greater relative hazard than in patients with impaired renal function.International journal of cardiology 01/2013; · 7.08 Impact Factor
Article: NFAT regulates the expression of AIF-1 and IRT-1: yin and yang splice variants of neointima formation and atherosclerosis.[show abstract] [hide abstract]
ABSTRACT: Alternative transcription and splicing of the allograft inflammatory factor-1 (AIF-1) gene results in the expression of two different proteins: AIF-1 and interferon responsive transcript-1 (IRT-1). Here, we explore the impact of AIF-1 and IRT-1 on vascular smooth muscle cell (VSMC) activation and neointima formation, the mechanisms underlying their alternative splicing, and associations of AIF-1 and IRT-1 mRNA with parameters defining human atherosclerotic plaque phenotype. Translation of AIF-1 and IRT-1 results in different products with contrasting cellular distribution and functions. Overexpression of AIF-1 stimulates migration and proliferation of human VSMCs, whereas IRT-1 exerts opposite effects. Adenoviral infection of angioplasty-injured rat carotid arteries with AdAIF-1 exacerbates intima hyperplasia, whereas infection with AdIRT-1 reduces neointima. Expression of these variants is modulated by changes in nuclear factor of activated T-cells (NFAT) activity. Pharmacological inhibition of NFAT or targeting of NFATc3 with small interfering RNA (siRNA) lowers the AIF-1/IRT-1 ratio and favours an anti-proliferative outcome. NFAT acts as a repressor on the IRT-1 transcriptional start site, which is also sensitive to interferon-γ stimulation. Expression of AIF-1 mRNA in human carotid plaques associates with less extracellular matrix and a more pro-inflammatory plaque and plasma profile, features that may predispose to plaque rupture. In contrast, expression of IRT-1 mRNA associates with a less aggressive phenotype and less VSMCs at the most stenotic region of the plaque. Inhibition of NFAT signalling, by shifting the AIF-1/IRT-1 ratio, may be an attractive target to regulate the VSMC response to injury and manipulate plaque stability in atherosclerosis.Cardiovascular research 11/2011; 93(3):414-23. · 5.80 Impact Factor