Reduction In Coronary Heart Disease Events Research Articles

Aspirin and Cardiovascular Risk in Individuals With Elevated Lipoprotein(a): The Multi-Ethnic Study of Atherosclerosis.

Effective therapies for reducing cardiovascular disease (CVD) risk in people with elevated lipoprotein(a) are lacking, especially for primary prevention. Because of the potential association of lipoprotein(a) with thrombosis, we evaluated the relationship between aspirin use and CVD events in people with elevated lipoprotein(a). We used data from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of baseline cardiovascular disease. Due to potential confounding by indication, we matched aspirin users to nonusers using a propensity score based on CVD risk factors. We then evaluated the association between aspirin use and coronary heart disease (CHD) events (CHD death, nonfatal myocardial infarction) stratified by baseline lipoprotein(a) level (threshold of 50 mg/dL) using Cox proportional hazards models with adjustment for CVD risk factors. After propensity matching, the study cohort included 2183 participants, including 1234 (57%) with baseline aspirin use and 423 (19%) with lipoprotein(a) >50 mg/dL. Participants with lipoprotein(a) >50 mg/dL had a higher burden of CVD risk factors, more frequent aspirin use (61.7% versus 55.3%, P=0.02), and higher rate of incident CHD events (13.7% versus 8.9%, P<0.01). Aspirin was associated with a significant reduction in CHD events among those with elevated lipoprotein(a) (hazard ratio, 0.54 [95% CI, 0.32-0.94]; P=0.03). Those with lipoprotein(a) >50 mg/dL and aspirin use had similar CHD risk as those with lipoprotein(a) ≤50 mg/dL regardless of aspirin use. Aspirin use was associated with a significantly lower risk for CHD events in participants with lipoprotein(a) >50 mg/dL without baseline CVD. The results of this observational propensity-matched study require confirmation in studies with randomization of aspirin use.

Abstract 11374: Aspirin for Primary Prevention of Cardiovascular Events in Patients With Elevated Lipoprotein(a): The Multi-Ethnic Study of Atherosclerosis

Introduction: There is a lack of effective therapies for reducing risk in people with elevated Lp(a), especially for primary prevention. We aimed to evaluate the association between aspirin use and cardiovascular events (CVD) in people with elevated Lp(a). Methods: We performed a prospective cohort study using data from participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of baseline cardiovascular disease. We matched aspirin users and non-users using a propensity score based on CVD risk factors. We then evaluated the association between aspirin use and coronary heart disease (CHD) events (CHD death, non-fatal myocardial infarction) stratified by baseline Lp(a) level (above and below 50 mg/dL) using Cox proportional hazards models with adjustment for CVD risk factors. Results: Our study cohort included 6,632 participants, including 1,138 (20%) with Lp(a) &gt;50 mg/dL and 1,592 (24%) with baseline aspirin use. Participants with elevated Lp(a) had a higher burden of CVD risk factors, with a trend toward greater aspirin use (25.7% vs 23.6%, p=0.10) and significantly higher CHD events (9.0% vs 7.3%, p=0.03). After propensity matching, aspirin was associated with a significant reduction in CHD events among those with elevated Lp(a) (HR 0.54, 95% CI 0.32-0.94, p=0.03). Those with Lp(a) &gt;50 mg/dL with aspirin use had similar freedom from CHD as those with Lp(a) ≤50 mg/dL regardless of aspirin use ( Figure ). Conclusions: Aspirin use was associated with a significant reduction in CHD events in participants with elevated Lp(a) without baseline CVD. These results are hypothesis generating and require confirmation in studies with randomization of aspirin use.

HDL Is Not Dead Yet.

High-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with coronary heart disease (CHD) in multiple epidemiological studies, but whether HDL is causal or merely associated with CHD is unclear. Recent trials for HDL-raising drugs were either not effective in reducing CHD events or, if beneficial in reducing CHD events, were not conclusive as the findings could be attributed to the drugs’ LDL-reducing activity. Furthermore, the first large Mendelian randomization study did not causally relate HDL-C levels to decreased CHD. Thus, the hypothesis that HDL is protective against CHD has been rightfully challenged. However, subsequent Mendelian randomization studies found HDL characteristics that are causally related to decreased CHD. Many aspects of HDL structure and function, especially in reverse cholesterol transport, may be better indicators of HDL’s protective activity than simply measuring HDL-C. Cholesterol efflux capacity is associated with lower levels of prevalent and incident CHD, even after adjustment for HDL-C and apolipoprotein A-1 levels. Also, subjects with very high levels of HDL-C, including those with rare mutations that disrupt hepatic HDL uptake and reverse cholesterol transport, may be at higher risk for CHD than those with moderate levels. We describe here several cell-based and cell-free in vitro assays of HDL structure and function that may be used in clinical studies to determine which of HDL’s functions are best associated with protection against CHD. We conclude that the HDL hypothesis may need revision based on studies of HDL structure and function, but that the HDL hypothesis is not dead yet.

LPA Variants Are Associated With Residual Cardiovascular Risk in Patients Receiving Statins.

Coronary heart disease (CHD) is a leading cause of death globally. Although therapy with statins decreases circulating levels of low-density lipoprotein cholesterol and the incidence of CHD, additional events occur despite statin therapy in some individuals. The genetic determinants of this residual cardiovascular risk remain unknown. We performed a 2-stage genome-wide association study of CHD events during statin therapy. We first identified 3099 cases who experienced CHD events (defined as acute myocardial infarction or the need for coronary revascularization) during statin therapy and 7681 controls without CHD events during comparable intensity and duration of statin therapy from 4 sites in the Electronic Medical Records and Genomics Network. We then sought replication of candidate variants in another 160 cases and 1112 controls from a fifth Electronic Medical Records and Genomics site, which joined the network after the initial genome-wide association study. Finally, we performed a phenome-wide association study for other traits linked to the most significant locus. The meta-analysis identified 7 single nucleotide polymorphisms at a genome-wide level of significance within the LPA/PLG locus associated with CHD events on statin treatment. The most significant association was for an intronic single nucleotide polymorphism within LPA/PLG (rs10455872; minor allele frequency, 0.069; odds ratio, 1.58; 95% confidence interval, 1.35-1.86; P=2.6×10-10). In the replication cohort, rs10455872 was also associated with CHD events (odds ratio, 1.71; 95% confidence interval, 1.14-2.57; P=0.009). The association of this single nucleotide polymorphism with CHD events was independent of statin-induced change in low-density lipoprotein cholesterol (odds ratio, 1.62; 95% confidence interval, 1.17-2.24; P=0.004) and persisted in individuals with low-density lipoprotein cholesterol ≤70 mg/dL (odds ratio, 2.43; 95% confidence interval, 1.18-4.75; P=0.015). A phenome-wide association study supported the effect of this region on coronary heart disease and did not identify noncardiovascular phenotypes. Genetic variations at the LPA locus are associated with CHD events during statin therapy independently of the extent of low-density lipoprotein cholesterol lowering. This finding provides support for exploring strategies targeting circulating concentrations of lipoprotein(a) to reduce CHD events in patients receiving statins.

No evidence to support high-intensity statin in Chinese patients with coronary heart disease

No evidence to support high-intensity statin in Chinese patients with coronary heart disease

Preventable Coronary Heart Disease Events from Control of Cardiovascular Risk Factors in US Adults With Diabetes (Projections from Utilizing the UKPDS Risk Engine)

Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal.

A Cost Effectiveness Analysis of Salt Reduction Policies to Reduce Coronary Heart Disease in Four Eastern Mediterranean Countries

BackgroundCoronary Heart Disease (CHD) is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey.Methods and FindingsThree policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG) over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy). All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30%) resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia; $39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and $1,3000,000,000 and 378439 LYG in Turkey.ConclusionDecreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives.

Coronary Heart Event Analysis with Association Rule Mining

Coronary heart disease (CHD) is one of the major causes of disability in adults as well as one of the main causes of death in the developed countries. Although significant progress has been made in the diagnosis and treatment of CHD, further investigation is still needed. The objective of this study was to develop the assessment of heart event-risk factors targeting in the reduction of CHD events using Association Rule Mining. The risk factors investigated were: 1) before the event: a) non modifiable—age, sex, and family history for premature CHD, b) modifiable—smoking before the event, history of hypertension, and history of diabetes; and 2) after the event: modifiable—smoking after the event, systolic blood pressure, diastolic blood pressure, total cholesterol, high density lipoprotein, low-density lipoprotein, triglycerides, and glucose. The events investigated were: myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABG).Data-mining analysis was carried out using the Association Rule Mining for the afore mentioned three events using five different splitting criteria for larger datasets. The most important risk factors, as extracted from the classification rules analysis were: 1) for MI, age, smoking, and history of hypertension; 2) for PCI, family history, history of hypertension, and history of diabetes; and 3) for CABG, age, history of hypertension, and smoking. It is anticipated that data mining could help in the identification of high and low risk subgroups of subjects, a decisive factor for the selection of therapy, i.e., medical or surgical.

A Meta-Analysis of Mental Health Treatments and Cardiac Rehabilitation for Improving Clinical Outcomes and Depression Among Patients With Coronary Heart Disease

To quantify the efficacy of mental health (antidepressants & psychotherapies) and cardiac rehabilitation treatments for improving secondary event risk and depression among patients with coronary heart disease (CHD). Using meta-analytic methods, we evaluated mental health and cardiac rehabilitation therapies for a) reducing secondary events and 2) improving depression severity in patients with CHD. Key word searches of PubMed and Psychlit databases and previous reviews identified relevant trials. Eighteen mental health trials evaluated secondary events and 22 trials evaluated depression reduction. Cardiac rehabilitation trials for the same categories numbered 17 and 13, respectively. Mental health treatments did not reduce total mortality (absolute risk reduction [ARR] = -0.001, confidence interval [95% CI] = -0.016 to 0.015; number needed to treat [NNT] = ∞), showed moderate efficacy for reducing CHD events (ARR = 0.029, 95% CI = 0.007 to 0.051; NNT = 34), and a medium effect size for improving depression (Cohen d = 0.297). Cardiac rehabilitation showed similar efficacy for treating depression (d = 0.23) and reducing CHD events (ARR = 0.017, 95% CI = 0.007 to 0.026; NNT = 59) and reduced total mortality (ARR = 0.016, 95% CI = 0.005 to 0.027; NNT = 63). Among patients with CHD, mental health treatments and cardiac rehabilitation may each reduce depression and CHD events, whereas cardiac rehabilitation is superior for reducing total mortality risk. The results support a continued role for mental health treatments and a larger role for mental health professionals in cardiac rehabilitation.

Analyzing the Coronary Heart Events Based on Weighted Association Rule Mining

Coronary heart disease (CHD) is one of the major causes of disability in adults as well as one of the main causes of death in the developed countries. Although significant progress has been made in the diagnosis and treatment of CHD, further investigation is still needed. The objective of this study was to develop the assessment of heart event-risk factors targeting in the reduction of CHD events using Weighted Association Rule Mining. The risk factors investigated were: 1) before the event: a) nonmodifiable—age, sex, and family history for premature CHD, b) modifiable—smoking before the event, history of hypertension, and history of diabetes; and 2) after the event: modifiable—smoking after the event, systolic blood pressure, diastolic blood pressure, total cholesterol, highdensity lipoprotein, low-density lipoprotein, triglycerides, and glucose. The events investigated were: myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABGData-mining analysis was carried out using the Weighted Association Rule Mining for the afore mentioned three events using five different splitting criteria.

Most Important Outcomes Research Papers on Cardiovascular Disease in Women

Cardiovascular disease (CVD) in women has been historically understudied. For many years, heart disease had been thought to be primarily a “man’s disease.” Consequently, women have been significantly under-represented in longitudinal studies of disease history and in clinical trials. High-quality data from women at the extremes of age, with multiple co-morbidities, and from racial and ethnic minorities have been particularly rare. In order to increase awareness of cardiovascular prevention among women, in 1999 the American Heart Association (AHA) published its first women-specific clinical recommendations for the prevention of CVD.1 In 2004, the AHA and multiple other collaborating organizations subsequently sponsored “Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women,” which underwent updates in 2007 and 2011. As a result of these and other related initiatives, the rate of public awareness of CVD as the leading cause of death among US women has increased from 30% in 1997 to 54% in 2009.2 CVD-associated death among US women has declined significantly over this time period.3,4 Yet substantial work still needs to be done to improve women’s cardiovascular health. CVD remains the number one killer among women.4 As the obesity epidemic continues, we are actually finding increases in coronary heart disease (CHD) death among young women 35 to 54 years of age.2 Morbidity and mortality from stroke and hypertension remain high.4 In addition, substantial outcomes disparities continue for women from racial and ethnic minorities.4 We have therefore dedicated our topic summaries in this issue of Circulation: Cardiovascular Quality and Outcomes to CVD in women. We have included only those studies where authors provided a convincing a priori reason to study a particular disease process or clinical intervention in women and reported primary endpoints that were sex-specific. We have included articles on the representation of women …

Genome-Wide Study of Gene Variants Associated with Differential Cardiovascular Event Reduction by Pravastatin Therapy

Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P<0.0001), and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8×10−7). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins.

WOMEN WITH CORONARY HEART DISEASE ARE LESS AGGRESSIVELY TREATED WITH LIPID LOWERING MEDICATIONS THAN MEN

Coronary heart disease (CHD) is the leading cause of death in women in the United States, and lipid-lowering therapy can reduce CHD events in women. Previous studies have shown that women are less likely to achieve optimal low-density lipoprotein (LDL) levels compared to men. We hypothesized that

Abstract P103: Genome-Wide Study of Gene Variants Associated with Differential Event Reduction by Pravastatin Therapy

BACKGROUND : Statin therapy reduces the risk of coronary heart disease (CHD); however, the variability in response to statin therapy is not well understood. We investigated the effect of genetic variation on the reduction of CHD events by pravastatin therapy. METHODS : We genotyped 682 CHD cases from CARE and 383 CHD cases from WOSCOPS, two randomized placebo-controlled studies of pravastatin using the Illumina OMNI1 bead array. Single nucleotide polymorphisms (SNPs) that were associated with differential CHD event reduction by pravastatin therapy were investigated in PROSPER, a randomized placebo-controlled study of pravastatin in the elderly. RESULTS : A combined case-only analysis of CARE and WOSCOPS identified 62 SNPs associated with differential event reduction by pravastatin therapy (P int &lt;0.0001 for interaction between treatment and genotype in an additive model). We investigated 57 of these SNPs in PROSPER. In an analysis that included cases as well as non-cases of CARE, WOSCOPS, and PROSPER, we found that for an intronic SNP in DNAJC5B (rs13279522), CHD event reduction by pravastatin therapy according to genotype differed in all 3 studies: P int =0.001 in CARE, P int =0.01 in WOSCOPS, P int =0.002 in PROSPER, and P int =3X10 -7 in a combined analysis of CARE, WOSCOPS and PROSPER (Figure). CONCLUSIONS : We have identified a SNP that is associated with differential event reduction by pravastatin therapy in CARE, WOSCOPS, and PROSPER. This SNP merits investigation in additional randomized studies of pravastatin and other statins.

Genetic Variants in the Apolipoprotein(a) Gene and Coronary Heart Disease

Two independent single-nucleotide polymorphisms (SNPs) in the gene encoding apolipoprotein(a) ( LPA ) have been shown to be associated with coronary heart disease (CHD) and lipoprotein(a) levels in Caucasians. For the missense SNP rs3798220 (Ile4399Met), carriers of 1 or 2 copies of the minor allele (Met) were at 57% increased risk of CHD. For the intronic SNP rs10455872, the risk of CHD increased by 42% for each copy of the minor allele. The rs3798220 SNP was also associated with differential response to aspirin therapy in the Women's Health Study; carriers of the minor allele had a significant reduction in CHD events from aspirin therapy, whereas noncarriers did not have a significant reduction. Lipoprotein(a) [Lp(a)] is a lipoprotein particle that consists of an apolipoprotein(a) [apo(a)] molecule covalently linked by a disulfide bond to the apolipoprotein B-100 (apoB-100) component of a low-density lipoprotein (LDL)-like particle (Figure 1, modified on the Albers et al1 figure). The LPA gene, which encodes apo(a), is thought to have been generated by a duplication of the neighboring plasminogen gene.2 Like the plasminogen protein, the apo(a) has a protease-like domain and multiple kringle domains. Different variants of the LPA gene can affect the plasma level of Lp(a), encode apo(a) size variants (ie, kringle repeat length variations), or both. Figure 1. Apolipoprotein(a) [apo(a)] gene structure and lipoprotein(a) [Lp(a)] particle model. Top panel shows the LPA exons (denoted by vertical boxes) along the 135-kbp genomic region on chromosome 6 (positions 160,872,506 at the right end to 161,007,397 at the left end) and the relative locations of the 2 single-nucleotide polymorphisms and protein domains (based on the HapMap Data Rel28 [http://www.hapmap.org]). Bottom panel depicts an Lp(a) particle that consists of an LDL-like particle, apoB-100, and apo(a) with annotation of the kringle repeats and the Ile4399Met polymorphism (modified on the Albers …

Primary Prevention of Coronary Heart Disease With Statins

In the current issue of Circulation , Lazar et al report the results of their modeling of the cost-effectiveness of alternative statin treatment strategies for primary prevention using low-cost, lower-potency generic statins.1 Lazar's study informs clinical decisions and practice guidelines about the potential use of statin therapy in people at low to moderate risk for coronary heart disease. It also provides an opportunity to consider the appropriate use and potential misuse of decision models to inform and guide clinical practice, and it highlights research opportunities, challenges, and potential limitations of comparative effectiveness, as well. Patients and providers commonly express the desire to make medical decisions solely on the basis of anticipated clinical benefits, harms, and patient preferences and values, without considering the distorting effects of cost. With the widespread availability of generic forms of most US-licensed statins (as of November 2011, rosuvastatin will be the only Food and Drug Administration-approved patent-protected statin in the United States), the cost of statin therapy has dropped precipitously. All currently available generic statins, with the exception of simvastatin 80 mg, can be purchased for as little $0.11 to $0.13 a pill at 1 or more major national pharmacy chains. Article see p 146 At these acquisition costs, Lazar et al find that low/moderate potency statin therapy is cost saving for those without a prior cardiovascular event at a moderately high risk of experiencing a coronary heart disease (CHD) event (10% to 20% over 10 years; 2 Framingham Heart Study [FHS] risk factors and a low-density lipoprotein-cholesterol [LDL-C] >100 mg/dL), and those with 2 risk factors but a 130 mg/dL, as well. They further identify a cost-effective maximum impact strategy that comprises all people with 2 Framingham risk factors, regardless of 10-year FHS risk or LDL-C level, those …

Two Single Nucleotide Polymorphisms in the Apolipoprotein(a) Gene are Predictors of the Risk of Coronary Heart Disease

Synopsis: Two single nucleotide polymorphisms (SNPs) in the apolipoprotein(a) [apo(a)] gene (LPA), rs3798220 (Ile4399Met) and rs10455872, are associated with lipoprotein(a) [Lp(a)] levels, apo(a) size, and coronary heart disease (CHD) in multiple studies. The Ile4399Met SNP is also associated with CHD event reduction by aspirin therapy.

Lipid-lowering Drug Therapy in Elderly Patients

Coronary heart disease (CHD) is the leading cause of death among elderly patients and >80% of all coronary deaths occur in patients >65 years. Cerebrovascular events are also associated with older age. Since elevated cholesterol concentrations are a risk factor for cardiovascular disease, lipid-lowering drugs, especially statins, are in widespread use for prevention. There is substantial underutilization of statins in the elderly population although meta-analyses of randomized trials have shown that in elderly secondary prevention patients they reduce all-cause mortality by approximately 22%, CHD mortality by 30%, non-fatal myocardial infarction (MI) by 26% and stroke by 25% over a treatment period of 5 years. Relative risk reduction is greater or at least equal to the one in younger patients, but absolute risk reduction is greater in the elderly because the event rate is higher. The benefit from statin treatment seems to start beyond 1 year of treatment. Data on primary prevention in the elderly are less clear. There is a significant reduction in CHD events, CHD deaths and all-cause mortality but numbers needed to treat (NNT) are higher than in secondary prevention. Treatment decisions have to consider the individual patient's situation regarding multimorbidity, polypharmacy and patient wishes. Economic considerations have to be made in some health systems. Statins have no role in the prevention or the treatment of dementia. Statins are generally safe and safety is equal in younger and older age groups. Their prescription should not be denied to patients for reasons of age alone. Other lipid-lowering drugs play only a minor role in cardiovascular disease (CVD) event prevention because convincing outcome studies are largely missing. A primary prevention statin trial in the very elderly is urgently needed.

Lasofoxifene and Cardiovascular Events in Postmenopausal Women With Osteoporosis

Background— In the Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial, women assigned to lasofoxifene 0.5 mg/d had a lower risk of major coronary heart disease (CHD) events and stroke, whereas women assigned to lasofoxifene 0.25 mg/d had a lower risk of stroke. Both doses of lasofoxifene increased the risk of venous thromboembolic events. In this report, we provide comprehensive cardiovascular end-point data, including component events comprising the composite end point of major CHD events, and evaluate whether the effect of lasofoxifene 0.5 mg/d is consistent across different categories of CHD risk. Methods and Results— In this study, 8556 women 59 to 80 years of age with osteoporosis received lasofoxifene 0.25 mg/d, lasofoxifene 0.5 mg/d, or placebo for 5 years. Cardiovascular events, including major CHD events, were prespecified secondary end points. Compared with placebo, lasofoxifene 0.5 mg/d reduced the risk of major CHD events 32% (hazard ratio, 0.68; 95% confidence interval, 0.50 to 0.93), including the risk of coronary revascularization (hazard ratio, 0.56, 95% confidence interval, 0.32 to 0.98). Reductions in risk of hospitalization for unstable angina (hazard ratio, 0.55; 95% confidence interval, 0.29 to 1.04) and diagnosis of new ischemic heart disease (hazard ratio, 0.52; 95% confidence interval, 0.26 to 1.04) nearly reached significance ( P =0.06 for both comparisons). Although both hazard ratios were &lt;1.0, no significant effect of lasofoxifene at 0.5 mg/d was demonstrated for coronary death or nonfatal myocardial infarction. The reduction in CHD events with lasofoxifene 0.25 mg/d was not significant (hazard ratio, 0.76; 95% confidence interval, 0.56 to 1.03; P =0.08). The effectiveness of lasofoxifene 0.5 mg/d in reducing CHD events was similar across strata of major cardiovascular risk factors. Conclusions— In postmenopausal women with osteoporosis, lasofoxifene 0.5 mg/d for 5 years reduced the risk of CHD events, regardless of the presence or absence of risk factors for cardiovascular disease. The significant reduction in risk of CHD events with lasofoxifene 0.5 mg/d was due primarily to lower risks of coronary revascularization procedures, hospitalization for unstable angina, and diagnosis of new ischemic heart disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00141323.

Dietary Salt Reduction Reduces Cardiovascular Disease

Research Article| June 01 2010 Dietary Salt Reduction Reduces Cardiovascular Disease AAP Grand Rounds (2010) 23 (6): 66. https://doi.org/10.1542/gr.23-6-66 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Dietary Salt Reduction Reduces Cardiovascular Disease. AAP Grand Rounds June 2010; 23 (6): 66. https://doi.org/10.1542/gr.23-6-66 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: cardiovascular diseases, dietary sodium chloride, salt intake, hypertension Source:, Bibbins-Domingo K, Chertow GM, Coxson PG, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med. 2010; 362(7): 590– 599; doi: https://doi.org/10.1056/NEJMoa0907355Google Scholar Investigators from the University of California, Stanford, and Columbia Universities used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). They estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; they compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and they determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medication. Reducing dietary salt by 3 g per day could reduce the annual number of new cases of CHD in the US by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000. This change could reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with African Americans benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. Cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. Salt reduction would be more cost-effective than using medications to lower blood pressure. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day could save $10 billion to $24 billion in health care costs annually. The authors conclude that reductions in dietary salt could sub-stantially reduce cardiovascular events and costs. They argue that salt reduction should be a public health priority. The FDA currently designates salt as a food additive that is “generally regarded as safe.” However, mounting evidence suggests that the current quantity of salt in a typical American diet can lead to significant health problems.1,2 The health risks of current levels of salt intake are similar to those of tobacco use, obesity, and hypercholesterolemia. The potential health benefits of changing salt intake are staggering, as is the economic impact projected from even modest adjustments in dietary consumption. Approximately 75% of the salt in American diets comes from processed foods. As a consequence, individuals have limited ability to reduce dietary sodium unless they eliminate consumption of processed foods. For individual families this is a desirable but often elusive goal. Therefore, the authors appropriately focus on the role of public health policy to reduce salt in food products consumed regularly by all Americans. While some food manufacturers are actively reducing the salt in their products, others are doing the opposite. In the UK a population-wide reduction in dietary salt of 10% was achieved over four years without a reduction in sales of the... You do not currently have access to this content.