Coronary Heart Disease Benefit Research Articles

Antithrombozytäre Therapie und Antikoagulation bei Patienten mit koronarer Herzerkrankung

Coronary heart disease (CHD) is a dynamic process with acute instable events and chronic periods leading to an increased mortality. Patients with CHD benefit from a differentiated antithrombotic therapy consisting of dual antiplatelet therapy in the acute phase and antiplatelet monotherapy or in combination with low dose anticoagulation (Xa-Inhibition) in the chronic phase. Current ESC-guidelines differentiate the acute coronary syndrome (ACS) and the chronic coronary syndrome (CCS). Depending on thrombotic burden, bleeding risk, comorbidities, such as atrial fibrillation, antiplatelet agents and oral anticoagulants in various combinations and dosages are used. In most scenarios in patients with ACS, the initial therapy will consist out of acetylsalicylic acid and a P2Y12-Inhibitor for 12 months followed by either a continuous monotherapy with acetylsalicylic acid (ASS), a prolonged dual antiplatelet therapy or a continuous dual antithrombotic therapy consisting of ASS and low dose rivaroxaban 2x daily. With atrial fibrillation as an underlying condition, an anticoagulant should be part of the therapy followed by anticoagulant monotherapy in the chronic phase of the disease (CCS). This article provides information about the different drugs and therapeutic algorithms based on the newest ESC-Guidelines and up to date studies.

Association Between Outdoor Light at Night and Risk of Coronary Heart Disease among 60,229 Older Adults: A Prospective Cohort Study

Background Light at night (LAN) is the most important environmental cue for circadian misalignment, which may increase risk of coronary heart disease through impairing circadian rhythms. We aimed to estimate the association between exposure to outdoor LAN and coronary heart disease (CHD) in elders.MethodsWe followed 60,229 Hong Kong elders free of CHD from 1998 through 2011. Annual LAN exposure was estimated using time-varying satellite data for a composite of persistent nighttime illumination at ~1 km2 scale for each residence. We used Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between exposure to outdoor LAN and risk of CHD. Results Over 10 to 13 years of follow-up, we identified 3,772 incident CHD cases and 1,695 CHD deaths. Annual levels of LAN at participants’ residential addresses ranged from 2.2 to 233.1 nW/cm2/sr. The concentration-response functions for the association between LAN and CHD incidence and mortality were approximate linear with the slopes becoming flat when LAN above 110 nW/cm2/sr. Per interquartile range (IQR) (60.0 nW/cm2/sr) increase in outdoor LAN, the HR was 1.09 (95% CI: 1.03, 1.17) for CHD incidence and 1.10 (95% CI: 1.01, 1.22) for CHD mortality after adjusting for both individual and area-level risk factors.Conclusions Exposure to outdoor light at night was associated with higher risk of coronary heart disease among Hong Kong elders. Our findings highlight the need to regulate light pollution for the potential coronary heart disease benefits.

Metabolic Profiling Analysis of Patients With Coronary Heart Disease Undergoing Xuefu Zhuyu Decoction Treatment.

Coronary heart disease (CHD) remains the leading cause of morbidity and mortality worldwide. Traditional Chinese medicine (TCM) is one of the effective complementary and alternative therapies used to improve the prognosis of CHD patients. Xuefu Zhuyu (XFZY) decoction, a classical traditional Chinese medication for regulating Qi and promoting blood circulation, has a clinical benefit in CHD; however, the underlying mechanism is not clear. Recently, it was found that the metabolites involved in amino acid metabolism and the tricarboxylic acid cycle were altered in CHD patients with Qi and Yin deficiency syndrome. To understand the material foundation of Qi, it is of great significance to study the differential metabolites involved in Qi during treatment of CHD with Qi-regulating and blood-promoting herbs. In this study, we investigated the metabolic profiles of serum in CHD patients by nontargeted metabolomics analysis to detect differential metabolites between the XFZY decoction group and placebo group. Ten CHD patients were enrolled and treated with placebo granules or XFZY decoction granules in a random and double-blind manner. Serum samples of all patients were evaluated by untargeted high-performance liquid chromatography with tandem mass spectrometry-based metabolomics. In total, 513 metabolites were detected in the serum of CHD patients, and six of these metabolites participating in seven metabolic pathways were significantly different between CHD patients treated with XFZY decoction and the placebo group. Among the six differential metabolites, FA (20:2)-H and tetracarboxylic acid (24:0), involved in fatty acid metabolism; cis-aconitic acid, which participates in the tricarboxylic acid cycle; 2-deoxy-D-glucose, involved in glucose metabolism; and N-acetylglycine, involved in amino acid metabolism, were decreased, whereas spermine, which participates in amino acid metabolism, was increased as compared with the placebo group. Our findings, combined with the perspective of biological functions, indicate that 2-deoxy-D-glucose and spermine might constitute the partial material foundation of Qi in CHD patients treated with XFZY decoction.

Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression.

Premenopausal atherosclerosis progression seems to be an important determinant of postmenopausal atherosclerosis and thus the risk for CHD. Clearly, plasma lipids/lipoproteins influence this progression; however, estradiol deficiency seems to be the major modulator. Both monkeys and women with premenopausal estrogen deficiency develop premature atherosclerosis, an effect that can be prevented in both species by estrogen-containing oral contraceptives. During this stage, there are robust estrogen benefits. Monkeys given estrogens immediately after surgical menopause have a 70% inhibition in coronary atherosclerosis progression. Estrogen treatment prevented progression of atherosclerosis of women in the Estrogen in the Prevention of Atherosclerosis Trial. A meta-analysis of women younger than 60 years given hormone therapy had reduced total mortality (relative risk = 0.61, 95% CI: 0.39-0.95). This stage is one in which there are no or possible deleterious estrogen effects. Monkeys lose CHD benefits of estrogens when treatment is delayed. The increase in CHD events associated with initiating hormone therapy 10 or more years after menopause seems to be related to up-regulation of the plaque inflammatory processes and plaque instability and may be down-regulated by statin pretreatment.

Trials and Tribulations of CETP Inhibitors.

The development of CETP (cholesteryl ester transfer protein) inhibitors has had a long and difficult course with 3 compounds failing in phase III clinical trials. Finally, the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid modification) trial has shown that the CETP inhibitor anacetrapib decreased coronary heart disease when added to statin therapy. Although the result is different to earlier studies, this is likely related to the size and duration of the trial. The benefit of anacetrapib seems to be largely explained by lowering of non-HDL-C (high-density lipoprotein cholesterol), rather than increases in HDL-C. Although the magnitude of benefit for coronary heart disease appeared to be moderate, in part this may have reflected aspects of the trial design. Anacetrapib treatment was associated with a small increase in blood pressure, but was devoid of major side effects and was also associated with a small reduction in diabetes mellitus. Treatment with CETP inhibitors, either alone or in combination with statins, could provide another option for patients with coronary disease who require further reduction in LDL (low-density lipoprotein) and non-HDL-C.

Low-fat dietary pattern and cardiovascular disease: results from the Women’s Health Initiative randomized controlled trial

Background: The influence of a low-fat dietary pattern on the cardiovascular health of postmenopausal women continues to be of public health interest.Objective: This report evaluates low-fat dietary pattern influences on cardiovascular disease (CVD) incidence and mortality during the intervention and postintervention phases of the Women's Health Initiative Dietary Modification Trial.Design: Participants comprised 48,835 postmenopausal women aged 50-79 y; 40% were randomly assigned to a low-fat dietary pattern intervention (target of 20% of energy from fat), and 60% were randomly assigned to a usual diet comparison group. The 8.3-y intervention period ended in March 2005, after which >80% of surviving participants consented to additional active follow-up through September 2010; all participants were followed for mortality through 2013. Breast and colorectal cancer were the primary trial outcomes, and coronary heart disease (CHD) and overall CVD were additional designated outcomes.Results: Incidence rates for CHD and total CVD did not differ between the intervention and comparison groups in either the intervention or postintervention period. However, CHD HRs comparing these groups varied strongly with baseline CVD and hypertension status. Participants without prior CVD had an intervention period CHD HR of 0.70 (95% CI: 0.56, 0.87) or 1.04 (95% CI: 0.90, 1.19) if they were normotensive or hypertensive, respectively (P-interaction = 0.003). The CHD benefit among healthy normotensive women was partially offset by an increase in ischemic stroke risk. Corresponding HRs in the postintervention period were close to null. Participants with CVD at baseline (3.4%) had CHD HRs of 1.47 (95% CI: 1.12, 1.93) and 1.61 (95% CI: 1.02, 2.55) in the intervention and postintervention periods, respectively. However, various lines of evidence suggest that results in women with CVD or hypertension at baseline are confounded by postrandomization use of cholesterol-lowering medications.Conclusions: CVD risk in postmenopausal women appears to be sensitive to a change to a low-fat dietary pattern and, among healthy women, includes both CHD benefit and stroke risk. This trial was registered at clinicaltrials.gov as NCT00000611.

Stenting the Non-Culprit Lesion during Primary Angioplasty of the Infarct-Related Coronary Artery: The Long and Winding Road

Submit Manuscript | http://medcraveonline.com J Cardiol Curr Res 2015, 4(3): 00141 treatment of choice for ST-segment elevation myocardial infarction (STEMI) [3]. Considering the fact that patients with multivessel coronary heart disease (CHD) comprise over half of the STEMI population, it is not an uncommon finding to observe a significant non-culprit lesion besides the occluded infarctrelated coronary artery during primary PCI. These patients with multivessel disease in this context have a worse prognosis than patients with single vessel disease [4,5]. Now, the problem is what to do with the non-culprit significant stenosis once the infarctrelated coronary artery was already treated. Should we proceed and stent the non-culprit lesion turning unstable a coronary plaque that was previously stable and jeopardize another wall in a patient that already has an infarcted territory? It seems logical to think that treating all significant coronary stenosis would provide a better clinical outcome. However, although there is recent data in favor of this therapeutic management, the 2013 ACCF/ AHA guidelines for the management of ST-elevation myocardial infarction discouraged this approach due to a significant increase in adverse outcomes for patients undergoing multivessel PCI in the setting of STEMI, and recommended a restrictive approach that discourages treatment of non-culprit lesions during the index PCI, unless the patient is in cardiogenic shock [6]. Moreover, the 2014 ESC/EACTS guidelines on myocardial revascularization are in accordance with the latter approach [7]. They stated that evidence supporting immediate (preventive) intervention in noninfarct-related lesions is a matter of debate [8,9]. On the other hand, patients with extensive CHD in vessels remote from the infarct-related artery have reduced success in reperfusion and an adverse prognosis following primary PCI [8]. They concluded that at present, multivessel PCI during STEMI should be considered in patients with cardiogenic shock in the presence of multiple, critical coronary stenosis, and if there is persistent ischemia after PCI on the supposed culprit lesion [6]. It is well known that patients with stable CHD and multivessel disease benefit from achieving complete revascularization [1013]. The question is if this assumption also holds true in the setting of STEMI if a more aggressive approach leading to more complete revascularization is performed. This is a controversial subject if we analyze current data based on observational studies and compare them to the results of recent randomized clinical trials in the era of drug eluting stents. In fact, observational data suggested that this approach was not beneficial and might be even harmful, with slightly better outcome depending on the timing of the nonculprit PCI [14,15]. On the other hand, recent evidence obtained from randomized trials documented significant reductions in composite ischemic endpoints by performing multivessel revascularization during STEMI [16,17]. However, there had been some inconsistencies in the analysis of the results. For example, the PRAMI (Preventive Angioplasty in Myocardial Infarction) trial [16], was stopped prematurely due to a much higher than expected treatment efficacy. They found a 65% reduction in ischemic events with complete revascularization during the index PCI in 465 patients. It seems a little surprising to achieve such high statistically significant results with a relatively small number of patients and of clinical events raising concerns of a chance finding magnified by the early termination of the trial. In addition, the CVLPRIT (Complete Versus Lesion-Only Primary PCI) trial [17] did not show reductions in hard endpoints, and the benefit demonstrated in the composite endpoint was obtained by repeat revascularizations. This open-label clinical trial randomized 296 patients in 7 UK centers to either inhospital complete revascularization (n: 150), or culprit lesiononly revascularization (n: 146). Complete revascularization was performed in the index hospitalization either at the time of primary PCI or before hospital discharge. The primary endpoint of mortality, recurrent myocardial infarction, heart failure, or ischemia-driven revascularization within 12 months occurred in Editorial

The Sydney Diet Heart Study: a randomised controlled trial of linoleic acid for secondary prevention of coronary heart disease and death

ObjectiveTo evaluate the effectiveness of replacing saturated fat (SFA) with omega‐6 linoleic acid (LA) for the secondary prevention of coronary heart disease (CHD) and death.BackgroundAdvice to substitute polyunsaturated fats (PUFAs) for SFA is a cornerstone of dietary guidelines. However, clinical CHD benefits of the most abundant PUFA, omega‐6 LA have not been established. A complete analysis of the effects of LA on CHD and CVD mortality has not previously been possible due to missing data from the Sydney Diet Heart Study (SDHS). We recovered the original SDHS dataset to fill two key evidence gaps by (1) reporting unpublished CHD and CVD mortality outcomes, and (2) updating our incomplete 2010 meta‐analysis of LA intervention trials.DesignRandomised controlled trial in 458 men with CHD.InterventionsThe intervention group replaced SFA with LA from safflower oil and safflower oil polyunsaturated margarine. The control group continued their habitual diet.ResultsThe intervention group had higher all‐cause (HR 1.62; 95%CI 1.00–2.64; p=0.051), CVD (HR 1.70; 95%CI 1.03–2.80; p=0.037) and CHD mortality (HR 1.74; 95%CI 1.04–2.92; p=0.036). An updated meta‐analysis of LA intervention trials showed concordant unfavorable effects for CHD and CVD death.ConclusionsSubstituting LA in place of SFA increased all‐cause, CVD and CHD mortality. Advice to increase LA or unspecified PUFAs merits reconsideration.Support:NIAAA

Food for Thought: Have We Been Giving the Wrong Dietary Advice?

Background: Since 1984 UK citizens have been advised to reduce total dietary fat intake to 30% of total energy and saturated fat intake to 10%. The National Institute of Clinical Excellence [NICE] suggests a further benefit for Coronary Heart Disease [CHD] prevention by reducing saturated fat [SFA] intake to 6% - 7% of total energy and that 30,000 lives could be saved by replacing SFAs with Polyunsaturated fats [PUFAs]. Methods: 20 volumes of the Seven Countries Study, the seminal work behind the 1984 nutritional guidelines, were assessed. The evidence upon which the NICE guidance was based was reviewed. Nutritional facts about fat and the UK intake of fat are presented and the impact of macronutrient confusion on public health dietary advice is discussed. Findings: The Seven Countries study classified processed foods, primarily carbohydrates, as saturated fats. The UK government and NICE do the same, listing biscuits, cakes, pastries and savoury snacks as saturated fats. Processed foods should be the target of public health advice but not natural fats, in which the UK diet is deficient. With reference to the macro and micro nutrient composition of meat, fish, eggs, and dairy foods the article demonstrates that dietary trials cannot change one type of fat for another in a controlled study. Interpretation: The evidence suggests that processed food is strongly associated with the increase in obesity, diabetes, CHD, and other modern illness in our society. The macro and micro nutrients found in meat, fish, eggs and dairy products, are vital for human health and consumption of these nutritious foods should be encouraged.

Lessons Learned From the Womenʼs Health Initiative Trials of Menopausal Hormone Therapy

We re-evaluate the Women's Health Initiative findings and their implications for clinical practice. Menopausal hormone therapy (HT) was effective for relief of vasomotor symptoms, and the risk of coronary heart disease (CHD) tended to be reduced in women close to menopause compared with the increased risk in women more distant from menopause. In recently menopausal women, short-term absolute risks of stroke and venous thromboembolism were small. Estrogen plus progestin therapy, but not estrogen therapy, increased the risk of breast cancer with a suggestion of greater risk when initiated close to the menopause. Menopausal HT increased the risk of CHD in women more than 20 years distant from menopause, particularly in women with vasomotor symptoms. It remains unknown whether the suggestive benefit for CHD in younger women will translate into benefits or harms if menopausal HT is continued into older ages. Based on Women's Health Initiative data, the use of menopausal HT for fewer than 5 years is a reasonable option for the relief of moderate to severe vasomotor symptoms. The risks seen with estrogen plus progestin therapy suggest careful periodic reassessment of the ongoing therapy needs for women taking estrogen plus progestin therapy. The more favorable profile of estrogen therapy allows for individualized management with respect to duration of use when symptoms persist. For both estrogen therapy and estrogen plus progestin therapy, the baseline risk profile of the individual woman needs to be taken into account. Menopausal HT is not suitable for long-term prevention of CHD given risks of stroke, venous thromboembolism, and breast cancer (for estrogen plus progestin therapy) found in both clinical trials and in observational studies.

Abstract ED01-02: Methodologic considerations for large-scale prevention trials: Lessons from the Women's Health Initiative

Abstract The Women's Health Initiative was one of the premiere primary prevention trials of its era. The core component was a partial factorial randomize trial designed to test three chronic disease prevention hypotheses in over 68,000 postmenopausal women: hormone therapy (HT) for the prevention of coronary heart disease; a low fat diet for the prevention of breast cancer and colorectal cancer, and calcium/vitamin D supplements for hip fracture risk reduction. This large diverse program provides useful lessons for many of the issues that arise in the design, implementation, analysis and interpretation of large-scale public health trials. The greatest public health impact of WHI has come from the two HT trials. The estrogen plus progestin trial in women with an intact uterus was stopped early, in 2002, based on an increased risk in breast cancer and overall health risks exceeding benefits. In 2004, the estrogen alone trial in women with prior hysterectomy, was stopped for an increased risk in stroke. These results were immediately translated into a public health message that had a rapid impact on HT use, followed shortly by a reduction in national breast cancer incidence rates. The HT trial results were considered highly controversial, however, because of their failure to show benefit for coronary heart disease, a hypothesis supported by numerous observational studies, animal studies, and randomized trials with intermediate outcomes. These contradictory findings fueled a persistent debate about the interpretation and integrity of the trial. Many of the purported flaws in the trial were easily refuted, owing to the strength of the trial's design, implementation and analyses. The design required excellent power for conservative projections of intervention effects. Key implementation factors included multicenter recruitment directly from the general population of postmenopausal women using broadly inclusive eligibility criteria, well-established, commonly used interventions, double-blinded trial conduct, ongoing support for adherence to interventions, broad-spectrum but prioritized outcomes ascertainment processes, standard of care safety monitoring including requirements for regular mammography, and a written trial monitoring plan to address the multiple testing for the numerous trial outcomes and interim analyses. To address these discrepancies between observational and randomized trial data directly, joint analyses of the WHI Observational Study (OS) and the HT trials were conducted. While the usual analysis of HT effects in the OS led to inferences similar to the preceding observational studies, analyses that carefully controlled for multiple confounders and took into account time from initiation of therapy and for breast cancer, time between menopause and first use of HT, yielded good alignment between the WHI HT trial and observational studies. These analyses yielded opposite trends with time for CHD and breast cancer, that is early initiators tended to have lower CHD risk but greater breast cancer risk than later initiators, providing some support for the so-called “timing hypothesis” yet confirming the limited utility of these agents for chronic disease prevention. Citation Format: Garnet L. Anderson. Methodologic considerations for large-scale prevention trials: Lessons from the Women's Health Initiative. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED01-02.

What place, if any, does information on putative cardioprotective effects of moderate alcohol use have in safer drinking guidelines?

The majority view among alcohol epidemiologists is that the lower coronary heart disease mortality observed in moderate drinkers is probably evidence for a protective effect of moderate drinking. In this paper I critically discuss the debate about what type of information, if any, should be provided to the public about the putative coronary heart disease benefits of moderate alcohol use. Most opposition to informing the public about these putative benefits is based on the fear that such advice will increase per capita alcohol consumption and therefore alcohol-related harm. It is unclear how well-based these concerns are. In the interim, the alcohol industry has communicated these putative benefits to the public. There is a case for including some information on these putative benefits in specific safer drinking guidelines for middle-aged and older drinkers that: clearly conveys the remaining uncertainty about the benefits of moderate drinking, emphasises the conditional nature of any such benefits, and stresses the need to balance the potential benefits against the increased sensitivity of older adults to other adverse effects of alcohol, and the increased risk of interactions between alcohol and other medications used by older adults.

Effects of Diet on High-Density Lipoprotein Cholesterol

Multiple dietary factors have been shown to increase high-density lipoprotein cholesterol (HDL-C) concentrations, and HDL-C has been inversely associated with coronary heart disease (CHD) risk. Replacement of dietary carbohydrate with polyunsaturated, monounsaturated and saturated fat has been associated with progressively greater increases in HDL-C (7-12%) in addition to other lipid changes. Added sugars, but not high glycemic carbohydrates, have been associated with decreased HDL-C. Alcohol consumption has been associated with increased HDL-C (9.2%) independent of changes in other measured lipids. Modest effects on HDL-C (~4-5%) among other lipid and non-lipid CHD risk factors have also been observed with weight loss by dieting, omega-3 fatty acids, and a Mediterranean diet pattern. The CHD benefit of increasing HDL-C is unclear given the inconsistent evidence from HDL-raising pharmacologic trials. Furthermore, pleiotropic effects of diet preclude attribution of CHD benefit specifically to HDL-C. Investigation into functional or other properties of HDL may lend further insight.

Coronary heart disease benefits from blood pressure and lipid-lowering

Background We have reported the benefits of atorvastatin and of an amlodipine-based regimen on coronary heart disease (CHD) events in hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We report further analyses on the combined benefits of these interventions. Methods 19,342 hypertensive patients were randomised to either an amlodipine or an atenolol-based regimen in the ASCOT Blood Pressure-Lowering Arm (BPLA). 10,305 subjects with total cholesterol ≤ 6.5 mmol/L were further randomised to atorvastatin 10 mg or placebo in the Lipid-Lowering Arm (LLA). Estimates of CHD risk at baseline based on the Framingham algorithm were compared with observed and predicted event rates throughout ASCOT-LLA. Results Estimated baseline Framingham risk of CHD events was 22.8 per 1000 patient years. After 3.3 years, when the LLA was stopped, the actual CHD event rate had fallen to 4.8 per 1000 patient years—a reduction of 79% in those assigned amlodipine-based treatment and atorvastatin. Conclusions CHD benefits associated with BP and lipid lowering were larger than predicted by previous observational and trial data. We estimate that compared with pre-trial treatment, treating about 55 patients with the amlodipine-based regimen and atorvastatin would prevent one CHD event per year.

Coronary heart disease and hormone replacement therapy after the menopause

The discordance in coronary heart disease (CHD) outcome between randomized, controlled trials and observational studies of hormone replacement therapy (HRT) is likely the result of the dissimilar cohorts studied. This observation led to the formation of the timing hypothesis that benefits and risks of HRT depend upon age of HRT initiation and/or time of HRT initiation in relation to menopause. This hypothesis has been supported with data from large, randomized, controlled trials that have studied HRT and selective estrogen receptor modulators (SERMs) in the prevention of CHD. Initiation of HRT in women <60 years of age and/or within 10 years of menopause reduces both CHD and total mortality; SERMs have been shown to reduce CHD in women <60 years. What has become clear from the cumulated literature is that in young postmenopausal women who initiate HRT in close proximity to menopause, the adverse effects of HRT are rare and no greater than those of other commonly used pharmacological agents and that the primary prevention benefits for CHD are at least equivalent to those of other commonly used therapies. Additionally, the literature indicates that the duration of HRT confers greater CHD benefit especially in women <60 years who initiate therapy. The cumulated literature dispels misperceptions concerning HRT and CHD.

The role of triglycerides in cardiovascular risk

Triglycerides' role in coronary heart disease (CHD) risk assessment has long been debated. Although meta-analyses have suggested that triglycerides are an independent risk factor for CHD, a consensus has emerged that triglycerides more appropriately represent a biomarker of CHD risk rather than an independent risk factor. Ongoing studies will determine whether triglyceride lowering confers additional CHD benefit beyond that attained via low-density lipoprotein (LDL) cholesterol reduction. The American Diabetes Association presently recommends lowering elevated triglycerides as a secondary therapeutic target after LDL cholesterol, whereas other organizations, such as the National Cholesterol Education Program, recommend non-high-density lipoprotein cholesterol as the second priority after attaining the LDL cholesterol goal. However, reducing very high triglycerides (ie, > 500 mg/dL) remains a sufficiently high priority in affected individuals.

Usefulness of Baseline Lipids and C-Reactive Protein in Women Receiving Menopausal Hormone Therapy as Predictors of Treatment-Related Coronary Events

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio <2.5 had no increase in risk of coronary heart disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio > or =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio <2.5 when predicting coronary heart disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio <2.5, did not have increased risk of coronary heart disease with CEE with or without MPA irrespective of hs-CRP.

Associations between high-density lipoprotein cholesterol and both stroke and coronary heart disease in the Asia Pacific region

The inverse relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease (CHD) is well established. Questions remain about the association between HDL cholesterol and stroke, particularly for stroke subtypes. Cox survival models were applied to individual participant data from 25 cohort studies (about 80 000 subjects), with a median of 6.8 years follow-up. After adjustment for age and regression dilution, hazard ratios (95% confidence intervals) for a 1 standard deviation (SD) lower level of HDL cholesterol (0.4 mmol/L) were: for CHD events, 1.39 (1.22-1.57); for ischaemic stroke, 0.90 (0.75-1.07), and for haemorrhagic stroke, 0.89 (0.74-1.07). As total cholesterol (TC) increased relative to HDL cholesterol, the risk of CHD increased, the risk of ischaemic stroke was unchanged but the risk of haemorrhagic stroke decreased. A 1 SD increase in TC/HDL cholesterol (1.63 units) was associated with a 27% decrease in the risk of haemorrhagic stroke (95% confidence interval, 7-44%). There is clear evidence of potential benefit for CHD of increases in HDL cholesterol and decreases in TC relative to HDL cholesterol, but no evidence of an association between either HDL cholesterol or TC/HDL cholesterol and ischaemic stroke. Increasing HDL cholesterol relative to TC may increase the risk of haemorrhagic stroke.

Pilot study of combined therapy with ω-3 fatty acids and niacin in atherogenic dyslipidemia

Background Niacin and ω-3 fatty acids (ω-3 FA) are both nutrients that reduce serum triglyceride and raise high-density lipoprotein cholesterol (HDL-C) levels when used at pharmacological doses. The possibility that these two agents, given in combination, might have additive effects on these lipid parameters has not been examined previously. In addition, the combination might prevent the rise in low-density lipoprotein (LDL)-C levels frequently seen with ω-3 FA treatment. Objective To determine the effect of therapy of niacin and ω-3 FA alone and in combination versus placebo on lipid parameters in subjects with atherogenic dyslipidemia. Methods In a pilot parallel group study, we studied 29 patients with atherogenic dyslipidemia who were assigned to either dual placebo (n = 7), ω-3 FA (3.4 g/d; n = 8), crystalline niacin (3 g/d; n = 7), or the combination (n = 7) for 12 weeks. Fasting lipid profiles were assessed before and after treatment. Results Changes in serum triglyceride levels from baseline were 10%, −2%, −17%, and −52%, respectively, while HDL-C concentrations rose by 4%, 10%, 18%, and 33%, respectively. Both of these results were statistically significantly different for combination therapy compared to changes with placebo and ω-3 FA monotherapy (analysis of variance with Tukey’s post-hoc test). No statistically significant changes were seen for LDL-C. Addition of ω-FA to niacin had no effect on niacin-induced flushing. Conclusion From this small pilot study, we conclude that combined therapy with niacin and ω-3 FA has beneficial effects on triglyceride and HDL-C levels, and use of these two agents in combination prevents the ω-3 FA-induced rise in LDL-C. Larger studies of this combination therapy are clearly warranted in patient populations with atherogenic dyslipidemia to assess not only lipid effects, but also potential coronary heart disease benefits.

Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression

The past several years have been marked by confusion and controversy concerning whether estrogens are cardioprotective. The issue is of utmost public health importance because coronary heart disease (CHD) remains the leading cause of death among postmenopausal women. Fortunately, a unifying hypothesis has emerged that reproductive stage is a major determinant of the effect of estrogens on atherosclerosis progression, complications, and plaque vulnerability. PREMENOPAUSAL YEARS: Premenopausal atherosclerosis progression seems to be an important determinant of postmenopausal atherosclerosis and thus the risk for CHD. Clearly, plasma lipids/lipoproteins influence this progression; however, estradiol deficiency seems to be the major modulator. Both monkeys and women with premenopausal estrogen deficiency develop premature atherosclerosis, an effect that can be prevented in both species by estrogen-containing oral contraceptives. PERIMENOPAUSAL/EARLY POSTMENOPAUSAL YEARS: During this stage, there are robust estrogen benefits. Monkeys given estrogens immediately after surgical menopause have a 70% inhibition in coronary atherosclerosis progression. Estrogen treatment prevented progression of atherosclerosis of women in the Estrogen in the Prevention of Atherosclerosis Trial. A meta-analysis of women younger than 60 years given hormone therapy had reduced total mortality (relative risk = 0.61, 95% CI: 0.39-0.95). LATE POSTMENOPAUSAL YEARS: This stage is one in which there are no or possible deleterious estrogen effects. Monkeys lose CHD benefits of estrogens when treatment is delayed. The increase in CHD events associated with initiating hormone therapy 10 or more years after menopause seems to be related to up-regulation of the plaque inflammatory processes and plaque instability and may be down-regulated by statin pretreatment.