Acute Coronary Syndromes in the Elderly.

The clinical evidence for treatment of acute coronary syndrome (ACS) in the elderly is less robust than in patients younger than 75 years. The elderly have the highest incidence of cardiovascular disease and frequently present with ACS. This number can be expected to increase over time because society is aging. Older adults often sustain unfavorable outcomes from ACS because of atypical presentation and delay in recognition. In addition, elderly patients commonly do not receive optimal guideline-directed ACS treatment. Owing to their high baseline risk of ischemic complications, the elderly also fare worse even with optimal ACS treatment as they frequently have more complex coronary disease, more comorbidities, less cardiovascular reserve, and a higher risk of treatment complications. They are also subjected to a broader range of pharmacologic treatment. Treatment complications can be mitigated to some extent by meticulous dose adjustment of antithrombotic and adjunctive therapies. While careful transitions of care and appropriate utilization of post-discharge secondary preventive measures are important in ACS patients of all ages, the elderly are more vulnerable to system errors and thus deserve special attention from the clinician.

The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db/db mice.

Vascular diseases frequently accompany diabetes mellitus. Based on the current understanding of atherosclerosis as an inflammatory disorder of the vascular wall, it has been speculated that diabetes may accelerate atherosclerosis by inducing a proinflammatory milieu in the vasculature. ANG II and bone morphogenic proteins (BMPs) have been implicated in vascular inflammation. We evaluated the effect of angiotensin receptor blockade by valsartan and BMP inhibition by noggin on markers of vascular inflammation in a mouse model of diabetes. Noggin had no effect on blood pressure but decreased serum glucose levels, whereas valsartan significantly decreased blood pressure, but not serum glucose. Both inhibitors reduced reactive oxygen species production in the aorta. Additionally, noggin and valsartan diminish gene transcription and protein expression of various inflammatory molecules in the vascular wall. These observations indicate that although both inhibitors block superoxide production and have similar effects on inflammatory gene expression, glycemia and blood pressure may represent a secondary target differentially affected by noggin and valsartan. Our data clearly identify the BMP pathway as a potentially potent therapeutic target in diabetic inflammatory vascular disease.

Management of hypertension in women.

A gender-specific approach to cardiovascular (CV) diseases has been practiced for decades, although not always to the advantage of women. Based on population data showing that women are at lower risk for CV events than men female gender has generally been regarded as a protective factor for CV disease. Unfortunately, CV risk assessment has therefore received less attention in women. Despite the lower absolute risk of CV events in women compared with age-matched men, the majority of women die from CV diseases. In absolute numbers, since 1984, more women than men died of CV disease each year. Most CV events occur in women with known traditional CV risk factors. Improving risk factor management in women of all ages therefore yields an enormous potential to reduce CV morbidity and mortality in the population. Aside from smoking cessation, hypertension (HTN) control is the single most important intervention to reduce the risk of future CV events in women. This review highlights peculiarities of HTN as they pertain to women, and points out where diagnosis and management of HTN may require a gender-specific focus.

Insulin-like growth factor-1 receptor expression masks the antiinflammatory and glucose uptake capacity of insulin in vascular smooth muscle cells.

OBJECTIVE: Insulin resistance of vascular smooth muscle cells (VSMCs) has been linked to accelerated atherosclerosis in diabetes; however, the effects of insulin on VSMCs remain controversial. Most VSMC insulin receptors are sequestered into insulin-insensitive hybrids with insulin-like growth factor-1 receptors (IGF1Rs). Thus we hypothesized that regulation of IGF1R expression may impact cellular insulin sensitivity. METHODS AND RESULTS: IGF1R expression was increased in aortas from diabetic mice. IGF1R overexpression in VSMCs impaired insulin-induced Akt phosphorylation. Conversely, IGF1R downregulation by siRNA allowed assembly of insulin holoreceptors, enhanced insulin-induced phosphorylation of its receptor, Akt, Erk1/2, and further augmented insulin-induced glucose uptake. IGF1R downregulation uncovered an insulin-induced reduction in activation of NF-kappaB and inhibition of MCP-1 upregulation in response to TNF-alpha. CONCLUSIONS: Downregulation of IGF1R increases the fraction of insulin receptors organized in holoreceptors, which leads to enhanced insulin signaling and unmasks potential antiinflammatory properties of insulin in VSMCs. Therefore, IGF1R, which is susceptible to feedback regulation by its own ligand, may represent a novel target for interventions designed to treat insulin resistance in the vasculature.

Cardiovascular disease prevention tailored for women.

Cardiovascular disease prevention is most effective when it is tailored for individual risk, since the benefit of any preventive intervention should outweigh its potential side effects and costs. Recognition of important gender differences in cardiovascular disease prevention has led to the formulation of specific guidelines for women. Based on a rigorous review of evidence, the 2007 American Heart Association guidelines for cardiovascular disease prevention in women differ little from the guidelines for men. The main difference pertains to the role of aspirin in primary cardiovascular prevention and to the appreciation of diabetes as a more detrimental risk factor in women than men. These guidelines provide a valuable framework to select the optimal preventive strategy for women of all ages, based on individual risk stratification, potentially supplemented with appropriate use of novel imaging modalities. Observational data continue to identify discrepancies between women and men, which target areas of need for future research.

Allopurinol attenuates left ventricular remodeling and dysfunction after experimental myocardial infarction: a new action for an old drug?

BACKGROUND: Accumulating evidence suggests a critical role for increased reactive oxygen species (ROS) production in left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). Increased expression of xanthine oxidase (XO), a major source of ROS, has recently been demonstrated in experimental and clinical heart failure; however, a potential role for LV remodeling processes remains unclear. We therefore studied the effect of long-term treatment with allopurinol, a potent XO inhibitor, on myocardial ROS production and LV remodeling and dysfunction after MI. METHODS AND RESULTS: Mice with extensive anterior MI (n=105) were randomized to treatment with either vehicle or allopurinol (20 mg x kg(-1) x d(-1) by gavage) for 4 weeks starting on day 1 after surgery. Infarct size was similar among the groups. XO expression and activity were markedly increased in the remote myocardium of mice after MI, as determined by electron spin resonance spectroscopy. Myocardial ROS production was increased after MI but markedly reduced after allopurinol treatment. Importantly, allopurinol treatment substantially attenuated LV cavity dilatation and dysfunction after MI, as assessed by echocardiography, and markedly reduced myocardial hypertrophy and interstitial fibrosis. CONCLUSIONS: The present study reveals a novel beneficial effect of treatment with allopurinol, ie, a marked attenuation of LV remodeling processes and dysfunction after experimental MI. Allopurinol treatment therefore represents a potential novel strategy to prevent LV remodeling and dysfunction after MI.

Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase.

BACKGROUND: Endothelial nitric oxide (eNO) bioavailability is severely reduced after myocardial infarction (MI) and in heart failure. Statins enhance eNO availability by both increasing eNO production and reducing NO inactivation. We therefore studied the effect of statin treatment on eNO availability after MI and tested its role for endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular (LV) dysfunction, remodeling, and survival after MI. METHODS AND RESULTS: Wild-type (WT) and eNO synthase (eNOS)-/- mice with extensive anterior MI were randomized to treatment with vehicle (V) or atorvastatin (Ator, 50 mg/kg QD by gavage) for 4 weeks starting on day 1 after MI. Ator markedly improved endothelium-dependent, NO-mediated vasorelaxation; mobilization of endothelial progenitor cells; and myocardial neovascularization of the infarct border in WT mice after MI while having no effect in eNOS-/- mice. LV dysfunction and interstitial fibrosis were markedly attenuated by Ator in WT mice, whereas no effect was observed in eNOS-/- mice after MI. Importantly, Ator significantly increased the survival rate during 4 weeks after MI in WT mice (Ator versus V, 80% versus 46%; P<0.01, n=75) but not in eNOS-/- mice (43% versus 48%; NS, n=42). CONCLUSIONS: These findings suggest that increased eNO availability is required for statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, LV dysfunction, interstitial fibrosis, and survival after MI. eNO bioavailability after MI likely represents an important therapeutic target in heart failure after MI and mediates beneficial effects of statin treatment after MI.