In-hospital initiation of statin therapy in patients with acute coronary events

After acute coronary events, patients remain at high risk for recurrent cardiovascular events and mortality. Despite the compelling scientific and clinical trial evidence that statin therapy reduces mortality in patients after acute coronary events, this life-saving therapy continues to be underutilized. It is now recognized that the setting in which statin therapy is initiated has a major impact on patient adherence. In-hospital initiation of statin therapy has been demonstrated to result in a markedly increased treatment rate, improved long-term patient compliance, more patients reaching low-density lipoprotein levels less than 100 mg/dL, and improved long-term clinical outcomes. As long-term risk reduction is seen with statin therapy irrespective of baseline low-density lipoprotein cholesterol, virtually all acute coronary event patients are candidates for statin treatment. In-hospital initiation of statin therapy may also reduce early clinical events in acute coronary syndrome patients, but further research is required before this is fully established. The adoption of in-hospital initiation of statin therapy as the standard of care for patients hospitalized with acute coronary events will dramatically improve treatment rates and thus substantially reduce the risk of future coronary events and prolong life in the large number of patients hospitalized each year.     

Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation

OBJECTIVES

We sought to investigate whether statin therapy affects the association between preprocedural C-reactive protein (CRP) levels and the risk for recurrent coronary events in patients undergoing coronary stent implantation.

BACKGROUND

Low-grade inflammation as detected by elevated CRP levels predicts the risk of recurrent coronary events. The effect of inflammation on coronary risk may be attenuated by statin therapy.

METHODS

We investigated a potential interrelation among statin therapy, serum evidence of inflammation, and the risk for recurrent coronary events in 388 consecutive patients undergoing coronary stent implantation. Patients were grouped according to the median CRP level (0.6 mg/dl) and to the presence of statin therapy.

RESULTS

A primary combined end point event occurred significantly more frequently in patients with elevated CRP levels without statin therapy (RR [relative risk] 2.37, 95% CI [confidence interval] [1.3 to 4.2]). Importantly, in the presence of statin therapy, the RR for recurrent events was significantly reduced in the patients with elevated CRP levels (RR 1.27 [0.7 to 2.1]) to about the same degree as in patients with CRP levels below 0.6 mg/dl and who did not receive statin therapy (RR 1.1 [0.8 to 1.3]).

CONCLUSIONS

Statin therapy significantly attenuates the increased risk for major adverse cardiac events in patients with elevated CRP levels undergoing coronary stent implantation, suggesting that statin therapy interferes with the detrimental effects of inflammation on accelerated atherosclerotic disease progression following coronary stenting.     

Repolarization measures and their relation to sex hormones in postmenopausal women with cardiovascular disease receiving hormone replacement therapy

Women are more susceptible to the development of Torsades de Pointes ventricular tachycardia and have a longer heart rate-corrected QT interval than men. A causal role for estrogen has been implicated. The purpose of this study was to investigate if hormone replacement therapy (HRT) resulted in any changes in noninvasive depolarization and repolarization measurements, and to study their relation to circulating concentrations of sex hormones. Sixty postmenopausal women with cardiovascular disease (mean age 59 +/- 7 years; range 44 to 75) were randomized to receive oral conjugated estrogens, transdermal estradiol-17-beta (both with addition of progestins), or placebo. QRS, QT, and JT intervals and their dispersion on 12-lead electrocardiograms were analyzed at baseline, and after 6 and 12 treatment cycles of HRT. Blood samples for analyses of serum concentration of estrogens and androgens were obtained on the same occasions. Neither mean RR, QT, QTc, JT, and JTc intervals, nor QT and JT dispersion changed during treatment. There was a significant inverse relation between the mean JTc interval and the serum concentration of estradiol-17-beta, independent of age, testosterone levels, and abdominal obesity. There was also a significant inverse relation between the change in androstenedione levels and the change in QT interval (Spearman -0.35, p = 0.028) or JT interval (Spearman -0.41, p = 0.009) at 6 treatment cycles compared with baseline. In conclusion, treatment with oral conjugated estrogens or transdermal estradiol-17-beta combined with progestins did not alter depolarization or repolarization measurements. However, the inverse relation between repolarization and androgens fits with an effect of androgens on repolarization in postmenopausal women.     

Cell adhesion molecules in relation to simvastatin and hormone replacement therapy in coronary artery disease.

AIMS: To assess the effect of simvastatin, hormone replacement therapy and their combination on soluble cell adhesion molecules and plasma lipids, in hypercholesterolaemic post-menopausal women with coronary artery disease. METHODS: We studied 16 post-menopausal women with coronary artery disease and hypercholesterolaemia (total cholesterol >200mg x dl(-1) and LDL cholesterol >130 mg x dl(-1)). We compared simvastatin (20 mg daily) with hormone replacement therapy (0.625 mg conjugated oestrogen and 2.5 mg medroxyprogesterone acetate daily) and their combination, in a randomized, crossover, placebo controlled study. Each treatment period was 8 weeks long with a 4 week washout interval between treatments. Circulating cell adhesion molecules and plasma lipids were evaluated at the end of each treatment period. RESULTS: All three active treatments--simvastatin, hormone replacement therapy and the combination therapy--significantly reduced total and LDL cholesterol, compared to placebo (P<0.001). Only hormone replacement therapy, alone and in combination with simvastatin, significantly decreased lipoprotein(a) when compared to placebo (P<0.05), whereas simvastatin had no significant effect. Likewise, hormone replacement therapy and the combination therapy significantly reduced the intercellular adhesion molecule (ICAM-1) plasma levels (P=0.03 and P=0.02, respectively), while simvastatin, which was superior to hormone replacement therapy in lowering total and LDL cholesterol, did not modify ICAM-1 levels; the combination therapy was not more effective than hormone replacement therapy alone in ICAM-1 reduction. Neither the effect, on any treatment when compared to placebo, of VCAM-1 nor E-selectin levels differed significantly. CONCLUSIONS: Hormone replacement therapy may limit the inflammatory response to injury by modulating the expression of cell adhesion molecules from the endothelial cells, possibly in association with lipoprotein (a) reduction.     

Effect of genetic variations in platelet glycoproteins Ibalpha and VI on the risk for coronary heart disease events in postmenopausal women taking hormone therapy

Millions of women still use postmenopausal hormone therapy (HT). We genotyped 2090 women in Heart and Estrogen/progestin Replacement Study for functional polymorphisms in GP1BA and GP6 and assessed the coronary heart disease (CHD) event rate over 5.8 years of follow-up. In patients receiving placebo, there was an increased CHD death/myocardial infarction (MI)/unstable angina (UA) event rate in carriers of the GP1BA -5C allele (adjusted [adj] P = .006). HT increased the hazard ratio (HR) of CHD events in patients with the GP1BA -5TT genotype by 16% and reduced the HR in patients with the TC+CC genotypes by 46% (adj interaction P < .001). HT reduced the HR in patients with the GP6 13254TT genotype by 17% but increased the HR in patients with the TC+CC genotypes by 35% (adj interaction P < .001). Furthermore, HT increased the HR of CHD events in patients with the GP1BA -5TT plus GP6 13254TC+CC genotypes by 57% and reduced the HR in patients with the GP1BA -5TC+CC plus GP6 13254TT genotypes by 55% (adj interaction P < .001). In postmenopausal women with established CHD, these polymorphisms of platelet genes were predictors of CHD events and significantly modified the effects of HT on CHD risk. It will be important to replicate these findings in other studies.     

Thrombogenic factors and recurrent coronary events.

BACKGROUND: Thrombosis is a pivotal event in the pathogenesis of coronary disease. We hypothesized that the presence of blood factors that reflect enhanced thrombogenic activity would be associated with an increased risk of recurrent coronary events during long-term follow-up of patients who have recovered from myocardial infarction. METHODS AND RESULTS: We prospectively enrolled 1045 patients 2 months after an index myocardial infarction. Baseline thrombogenic blood tests included 6 hemostatic variables (D-dimer, fibrinogen, factor VII, factor VIIa, von Willebrand factor, and plasminogen activator inhibitor-1), 7 lipid factors [cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, lipoprotein(a), apolipoprotein (apo)A-I, and apoB], and insulin. Patients were followed up for an average of 26 months, with the primary end point being coronary death or nonfatal myocardial infarction, whichever occurred first. The hemostatic, lipid, and insulin parameters were dichotomized into their top and the lower 3 risk quartiles and evaluated for entry into a Cox survivorship model. High levels of D-dimer (hazard ratio, 2.43; 95% CI, 1.49, 3.97) and apoB (hazard ratio, 1.82; 95% CI, 1.10, 3.00) and low levels of apoA-I (hazard ratio, 1.84; 95% CI, 1.10, 3.08) were independently associated with recurrent coronary events in the Cox model after adjustment for 6 relevant clinical covariates. CONCLUSIONS: Our findings indicate that a procoagulant state, as reflected in elevated levels of D-dimer, and disordered lipid transport, as indicated by low apoA-1 and high apoB levels, contribute independently to recurrent coronary events in postinfarction patients.     

Risk of hepatic vein thrombosis in relation to recent use of oral contraceptives. A case-control study

In a case-control study, we evaluated the relative risk of hepatic vein thrombosis among recent oral contraceptive users as compared with nonusers. Thirty-three cases of hepatic vein thrombosis affecting women aged 15-45 yr were collected between 1970 and 1983, and individually matched to 3 or 4 controls interviewed in 1982-1984. There were 18 recent oral contraceptive users among the 33 cases, and 44 recent oral contraceptive users among the 128 case-matched controls. The relative risk of hepatic vein thrombosis was 2.37 (95% confidence interval: 1.05-5.34, p less than 0.02). The relative risk of hepatic vein thrombosis is close to that of stroke, myocardial infarction, and venous thromboembolism among oral contraceptive users as compared with nonusers.     

Insulin resistance and postmenopausal hormone replacement therapy

Insulin resistance causes hyperglycemia by disturbing glucose uptake in the tissues and increasing hepatic glucose production. Hyperinsulinemia has a predictive role in the generation of type 2 diabetes in nondiabetic individuals. Both insulin resistance and the associated disturbances are responsible for increased cardiovascular risk. Women of reproductive age are protected from cardiovascular disease although in the postmenopausal period the risk becomes equal to that in men and exceeds that in men later on. This observation leads us to consider the role of estrogen deficiency in the pathogenesis of cardiovascular disease. Hormone replacement therapy (HRT) is a successful method in the management of certain clinical situations in postmenopausal women. The interactions among estrogen, menopause, and cardiovascular risk bring forth the question of whether the HRT affects insulin resistance or not. The studies so far have yielded controversial results. The overall results of recent reports indicate that postmenopausal HRT improves insulin resistance. However, the available evidence is not strong enough to suggest the use of postmenopausal HRT as a first-line therapeutic measure in the management of insulin resistance.     

Blood pressure control and hormone replacement therapy in postmenopausal women at risk for coronary heart disease

Background Coronary heart disease (CHD) in women is strongly associated with estrogen deprivation. For example, risk for CHD increases dramatically after menopause. However, the role of hormone replacement therapy (HRT) in CHD prevention currently is unresolved. To better understand CHD in women, the precise mechanisms by which estrogen affects circulatory function require clarification. Evidence suggests that exogenous estrogen may affect blood pressure (BP) control, but its interaction with other CHD risk factors has not been systematically characterized. The present study examines the role of mildly elevated resting BP, family history of CHD, and HRT on BP responses to stress in postmenopausal women. Methods Postmenopausal women on long-term HRT were recruited along with a control group of postmenopausal women not on HRT. These women were divided into higher versus lower risk for CHD on the basis of resting BP and family history of CHD. BP control mechanisms were assessed before, during, and after a computer-controlled laboratory stressor. Results Results indicate that women with elevated resting BP and positive family history of CHD have exaggerated BP reactivity to stress and that HRT inhibits this effect. Conclusions This study suggests that unmedicated postmenopausal women with mildly elevated resting BP and positive family history of CHD have altered BP control as indicated by exaggerated BP responses to stress. HRT eliminates the cumulative effect of resting BP and family history on BP reactivity, suggesting that the circulatory effects of estrogen replacement may operate, at least in part, through normalization of BP reactivity in higher-risk postmenopausal women. (Am Heart J 2002;143:711-7.)     

Myocardial blood flow and flow reserve in response to hormone therapy in postmenopausal women with risk factors for coronary disease

Estrogen has beneficial effects on markers of coronary heart disease (CHD) risk, but may increase overall CHD events. The effects of hormone therapy on vascular endothelial function have been mixed, and require further assessment. We studied the myocardial blood flow (MBF) response to postmenopausal combination hormone therapy (CHT) in postmenopausal women with risk factors for CHD. We performed dynamic [13N]ammonia positron emission tomography in 15 postmenopausal women in a 7-month placebo-controlled crossover trial of continuous conjugated equine estrogen/cyclical micronized progesterone. MBF was measured at rest, after sympathetic stimulation with the cold pressor test (CPT), and after i.v. adenosine infusion, to determine baseline, endothelium-dependent, and maximal flows, respectively. Response to CPT was neutral in all women at baseline (-0.51 +/- 27%). Adenosine induced a marked increase in MBF (161 +/- 111%). Treatment with 3 months of combined estrogen/progestin CHT did not change CPT or adenosine MBF responses. Myocardial flow reserve was unchanged as well. In this group of postmenopausal women at higher cardiovascular risk, no association was found between CHT assignment and change in MBF. Further study is needed to clarify the effects of CHT on the endothelium of women with presumably diseased vasculature.     

The relation of oxidized LDL autoantibodies and long-term hormone replacement therapy to ultrasonographically assessed atherosclerotic plaque quantity and severity in postmenopausal women

BACKGROUND: In epidemiologic studies, the incidence of atherosclerosis rises soon after menopause in women, and hormone replacement therapy (HRT) has proved to be useful in preventing onset of clinical manifestations of the disease. However, it is not known how HRT affects sonographically determined atherosclerotic severity (AS) and number of atherosclerotic plaques (NAP) in large arteries. Furthermore, it is not clear how HRT affects oxidation of low density lipoproteins (LDL), which obviously has an important role in the pathogenesis of atherosclerosis. OBJECTIVES: The purpose of the study was to determine whether HRT has a beneficial effect on sonographically determined AS and NAP in large arteries of 101 postmenopausal women compared to 40 controls without HRT. We also studied the interaction of HRT and antibodies against oxidized LDL on AS and NAP progression. RESULTS: Estradiol valerate alone, combined estradiol valerate-levonorgestrel and combined estradiol valerate-medroxyprogesterone acetate therapy are each associated with lower NAP and AS as compared to controls without HRT. In a multiple regression model explaining NAP in the whole study population, the strongest predictors were HRT (P=0.0006) and copper-oxidized LDL cholesterol autoantibodies (P=0.0491). DISCUSSION: Our findings indicate that postmenopausal HRT is associated with a lower total number of atherosclerotic plaques and less severe atherosclerotic lesions, as compared to controls without HRT, and that this outcome may be associated with the effect of HRT on LDL cholesterol oxidation.