Common Cardiovascular Medications Research Articles

Abstract 197: Statin Therapy Is Associated With Higher MTHFR Methylation Levels in a Stroke Cohort

Introduction: Epigenetics refers to changes in gene function that occur by gene methylation, histone modification or RNA mechanisms. Many of these are heritable, but can also be altered by lifestyle and medication. Genome-wide hypomethylation is associated with atherosclerosis and hyperhomocysteinemia, and specific genes can be hyper or hypomethylated in vascular disease. Statins have pleiotropic effects on the vasculature, and may affect DNA methylation. Hypothesis: The methylation levels of genes implicated in vascular disease are altered by treatment with common cardiovascular medications. Methods: 189 individuals from a well characterised stroke cohort and controls were included. 44 were established on statin therapy, 49 on aspirin and 28 on an ACE inhibitor. The following genes implicated in vascular disease were investigated: LINE1, SOD3, ALOX15, ERa, MTHFR , PITX2, IFNGR1, TNFa, IL10, and INS . Methylation status was assessed by bisulphite conversion of DNA followed by PCR and pyrosequencing. Each methylation site was analysed individually and mean methylation level across all sites within a gene calculated. Statistical analysis for the effect of drug therapy was based on logistic regression and ANOVA. Results: One significant association was found: subjects on statin therapy had higher MTHFR methylation levels than those not receiving statin (p=0.002). Statistical analysis adjusted for stroke effect (p=0.025) remained significant. Correction for multiple testing was not performed as the candidate genes are linked in pathways. There was no effect of aspirin or ACE inhibitor on methylation status of any of the genes tested. Discussion: MTHFR plays an important role in homocysteine and folate metabolism, providing methyl groups for DNA methylation. High levels of homocysteine are a risk factor for cardiovascular disease and there is published evidence that statin therapy results in lower plasma homocysteine levels. This finding requires further investigation in a larger cohort with a defined dose and duration of treatment. If this finding is replicated, there may be value in exploring the mechanisms linking statins, MTHFR methylation and homocysteine levels and the implications for primary and secondary prevention of vascular events.

Clot properties and cardiovascular disease.

Fibrinogen is cleaved by thrombin to fibrin, which provides the blood clot with its essential structural backbone. As an acute phase protein, the plasma levels of fibrinogen are increased in response to inflammatory conditions. In addition to fibrinogen levels, fibrin clot structure is altered by a number of factors. These include thrombin levels, treatment with common cardiovascular medications, such as aspirin, anticoagulants, statins and fibrates, as well as metabolic disease states such as diabetes mellitus and hyperhomocysteinaemia. In vitro studies of fibrin clot structure can provide information regarding fibre density, clot porosity, the mechanical strength of fibres and fibrinolysis. A change in fibrin clot structure, to a denser clot with smaller pores which is more resistant to lysis, is strongly associated with cardiovascular disease. This pathological change is present in patients with arterial as well as venous diseases, and is also found in a moderate form in relatives of patients with cardiovascular disease. Pharmacological therapies, aimed at both the treatment and prophylaxis of cardiovascular disease, appear to result in positive changes to the fibrin clot structure. As such, therapies aimed at 'normalising' fibrin clot structure may be of benefit in the prevention and treatment of cardiovascular disease.

Cross-sectional study of indices of dynamic components of ambulatory blood pressure and cardiac damage in elderly male patients with essential hypertension

Blood pressure control is closely related to target organ damage in elderly patients with hypertension. The aim of this study was to determine the relationship between ambulatory blood pressure monitoring (ABPM) indices and cardiac damage in elderly male patients with treated essential hypertension (EH). This study included 998 Chinese men (mean age, 78.44 ± 12.02 years) with EH. Participants underwent cardiac function assessment, laboratory testing, and ABPM, including ABP, BP variability, BP circadian rhythms, and hypertensive or hypotensive time indices. The relationships between ABPM indices and cardiac damage (expressed by shape and function) were assessed using ridge regression analysis. Ridge regression analysis revealed the following after adjustments for age, common cardiovascular risk factors, disease, and medications: N-terminal fragment pro-B-type natriuretic peptide was negatively correlated with the diastolic blood pressure nocturnal fall rate; the peak early/atrial velocity (E/A) ratio E/A ratio was negatively correlated with the 24 h mean systolic blood pressure (24 hmSBP), daytime SBP (dSBP), and nocturnal SBP (nSBP); and ejection fraction (EF) was negatively correlated with 24 h SBP percent time of elevation (24 hSBP PTE %) and 24 h DBP percent time of elevation (24 hDBP PTE %). Left ventricular mass (LVM) was positively correlated with the 24 hmSBP, dSBP, nSBP, 24 h mean pulse pressure (24 hmPP), day mean pulse pressure, and nocturnal mean arterial pressure, whereas LVM was negatively correlated with the NDBPF. Our study showed that the ABPM indices associated with cardiac damage may be regarded as an early predictive marker for cardiac function impairment in elderly male patients with EH.

Cardiovascular medications in angiogenesis—How to avoid the sting in the tail

Cancer and cardiovascular disease are the leading causes of death worldwide. Cardiovascular medications have recently been found to have favorable effects also for the treatment of noncardiovascular diseases, including cancer. In this review, we use a reverse bedside-to-bench approach to investigate the effects of common cardiovascular medications on tumor angiogenesis and vascular angiogenesis. Aspirin seems to reduce the risk of developing cancer, particularly colon cancer. However, whether the protective influence of aspirin is due to antiangiogenesis effect is still unclear. β-Blockers, which are normally used to reduce heart rate and prolong diastole, trigger an increase in stretch-associated release of proangiogenic growth factors thereby inducing angiogenesis. However, according to other studies β-blockers are able to inhibit angiogenesis via multiplicate mechanisms. Similarly, angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor blocker have controversial effects for the regulation of cell proliferation and angiogenesis. Statins can augment collateral vascular growth in ischemic tissues and restrict the development of cancer. So this topical anti-inflammatory drug seems to be of high value for further therapy. Finally, suggestions on how this pilot experience may guide the conduct of future preclinical investigations, and clinical trials are discussed.

P264 The prevalence of β-blocker prescription in COPD patients

IntroductionIschaemic heart disease (IHD) is a major cause of morbidity and mortality in COPD patients. Effective cardiovascular therapies may have significant impact in COPD populations. In particular, β-blockers have been...

Renal function, concomitant medication use and outcomes following acute coronary syndromes

Chronic kidney disease (CKD) is highly prevalent in patients with cardiovascular disease. We explored the associations of CKD with outcomes using combined data from two large acute coronary syndrome (ACS) trials. We also explored the associations of CKD with prescription patterns for common cardiovascular medications and the association of these prescription patterns with clinical outcomes. Patients were stratified by CKD stage using creatinine clearance (CrCl, ml/min) estimated by the modified MDRD equation using baseline core laboratory creatinine measures. Serum creatinine > or =1.5 mg/dl was an exclusion criterion for the SYMPHONY trials. Baseline characteristics and outcomes across CKD categories were compared and Cox proportional hazards regression was used to assess the relationship of renal insufficiency with clinical outcomes after adjusting for previously identified outcome predictors. Interactions between the use of specific medications and calculated CrCl were tested in the final Cox proportional hazards model predicting time to mortality. Of 13 707 patients analysed, 6840 had CKD stage I (CrCl > or =90 ml/min), 5909 stage II (CrCl 60-89 ml/min), 955 stage III (CrCl 30-59 ml/min) and three stage IV (CrCl <30 ml/min). Patients with more advanced CKD (III) were older, more often female, non-smokers and more likely to have co-morbid diseases including diabetes mellitus, hypertension and congestive heart failure. Cardiovascular medications were used less frequently in patients with CKD. Unadjusted survival was poorer in patients with CKD stages > or =II. In adjusted analyses, for those with CrCl < or =91, each 10 ml/min increase in CrCl was associated with a significantly decreased risk of mortality (hazards ratio 0.897, 95% confidence interval 0.815-0.986) (P = 0.024). The interaction between use of angiotensin-converting enzyme (ACE) inhibitors and CrCl was significantly associated with outcomes; the benefit of drug therapy was greater among patients with CKD. CKD is an independent predictor of risk among ACS patients, and is associated with less frequent use of proven medical therapies. More aggressive use of conventional cardiovascular therapies in patients with CKD and ACS may be warranted.

Treating Depression in Patients with Cardiovascular Disease

Cardiovascular disease and depression are intimately related illnesses. Cardiovascular mortality is more common in persons with depression, and depression following a myocardial infarction is associated with significantly poorer cardiac outcome. Safe and effective simultaneous treatment of depression and cardiovascular illness can be difficult because of the interplay between these conditions. We examine the evidence for cardiovascular effects of depression as well as the proposed mechanism for these effects. We also review the cardiovascular effects of antidepressant treatments and the mood-altering effects of common cardiovascular medications. Articles reviewed were derived from a Medline search of English-language articles published between 1970 and 1998 (search terms: cardiovascular disease, antidepressants, psychiatry, myocardial infarction, antihypertensive agents, depression).

Treating depression in patients with cardiovascular disease.

Cardiovascular disease and depression are intimately related illnesses. Cardiovascular mortality is more common in persons with depression, and depression following a myocardial infarction is associated with significantly poorer cardiac outcome. Safe and effective simultaneous treatment of depression and cardiovascular illness can be difficult because of the interplay between these conditions. We examine the evidence for cardiovascular effects of depression, as well as the proposed mechanism for these effects. We also review the cardiovascular effects of antidepressant treatments and the mood-altering effects of common cardiovascular medications. Articles reviewed were derived from a Medline search of English-language articles published between 1970 and 1998 (search terms: cardiovascular disease, antidepressants, psychiatry, myocardial infarction, antihypertensive agents, depression).

Managing the pregnant patient with heart disease

Pregnancy and its associated hemodynamic challenge presents potential risks to the patient with cardiac disease, whether acquired or congenital. The hematologic changes which occur during pregnancy include alterations in blood volume, hematocrit, and blood viscosity. There are also alterations in cardiac output and regional blood flow patterns. These hemodynamic alterations are associated with signs and symptoms which can be impressive yet benign, or can suggest poor outcome, depending on the underlying cardiovascular disorder. The clinician is faced with the sometimes difficult task of differentiating the benign from the dangerous while making appropriate management decisions. In this article, diagnosis and current management of many of the more common acquired and congenital cardiac abnormalities are discussed as they pertain to the gravid female. The effects of common cardiovascular medications in pregnancy are also briefly reviewed.