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Publications (233)
Background:
Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.
Methods:
In this...
Previous studies have shown that HDL isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of nitrated apolipoprotein AI (NT-apoAI). The significance of NT-apoAI in the pathogenesis of vascular diabetic complications is not well understood. We aimed to evaluate the re...
Background: LDL plays a key role in development and progression of atherosclerosis. Elevated LDL amplifies the atherosclerotic process but the significance of modified LDL in pathogenesis of vascular complications is unclear. We aimed to assess plasma modified LDL levels and their relationship with vascular function in African American diabetic pat...
Background: Diabetes is a robust risk factor for cardiovascular events which is marked in African Americans for reasons that may be attributed to socioeconomic and biologic vulnerabilities. Both structural (arterial thickening) and functional (arterial stiffness) abnormalities of the vasculature are predictive of incidental clinical events. Study o...
Patients with type 2 diabetes mellitus exhibit non-enzymatic glycation of lipoproteins that are considered proatherogenic modification contributing to increased susceptibility of patients with diabetes to atherosclerosis. We postulated that glycated lipoproteins might be associated with vascular outcome. To explore this, we studied the relationship...
Objective
In statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treate...
Rationale: Diabetes is highly prevalent among African Americans and poses a higher risk for vascular complications in this population. Although socioeconomic factors are well known to influence outcomes, true biologic differences in risk factor vulnerability have been suggested. Vascular complications have been traditionally viewed as either macrov...
Background:
-Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events in a secondary prevention population. We also estimated the potential risk reduction, as well as the residual risk, that can be achieved...
Statins may have nephroprotective as well as cardioprotective effects in patients with cardiovascular disease. In the Treating to New Targets (TNT) study (NCT00327691), patients with coronary heart disease (CHD) were randomized to atorvastatin 10- or 80-mg/day and followed for 4.9 years. The relationship between intra-study change in estimated glom...
The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.
We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unp...
Unlabelled:
Several plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We cond...
The link between elevated LDL-C levels and increased risk of coronary heart disease (CHD) events is well established. The primary hypothesis of Treating to New Targets (TNT) was that reducing LDL-C levels to well below 100 mg/dL (2.6 mmol/L) in stable CHD patients with modest LDL-C elevation could yield incremental clinical benefit. This hypothesis...
In the Treating to New Targets (TNT) study, 10,001 patients with stable CHD and LDL-C levels <130 mg/dL (3.4 mmol/L) were randomized to double-blind therapy with either atorvastatin 10 or 80 mg/day and were followed for a median of 4.9 years. The primary endpoint was an occurrence of a first major cardiovascular event, defined as CHD death, nonfata...
Background
Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.
Objectives
The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), no...
Lowering of low-density lipoprotein cholesterol levels is a worthwhile intervention in older (more than 65-70 years of age) subjects, since age itself is a powerful predictor of vascular disease risk. Although studies have not consistently demonstrated an overall beneficial effect on total mortality, cardiovascular morbidity and mortality are favor...
It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol (LDL-C) on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin...
Background:
Clinicians need to identify coronary artery disease patients for whom the benefits of high-dose versus usual-dose statin therapy outweigh potential harm. We therefore aimed to develop and validate a model for prediction of the incremental treatment effect of high-dose statins for individual patients in terms of reduction of 5-year abso...
Background: Studies show that renal function improves with statin therapy in coronary patients with CKD, but few studies show a relationship between cholesterol and CKD. As many patients with CKD have dyslipidemia there is a need to evaluate the relationship between lipoproteins and CKD.
Based on the cardiovascular (CV) outcomes derived predominantly from 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) trials, guidelines have set low-density lipoprotein (LDL) cholesterol targets at successively lower levels over time. Recent data have demonstrated that more-intensive statin therapy (and, consequently, lower LDL c...
To examine the effect of intensive lipid-lowering therapy on a composite cardiovascular outcome (cardiovascular disease [CVD]), consisting of mortality and morbidity end points, in patients with inflammatory joint disease (rheumatoid arthritis [RA], ankylosing spondylitis [AS], or psoriatic arthritis [PsA]) by post hoc analysis of 2 prospective tri...
Statin therapy has been associated with pancreatitis in observational studies. Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis.
To investigate associations between statin or fibrate therapy and inc...
To evaluate lipids and apolipoproteins as predictors of cardiovascular mortality and morbidity (CVD) in patients with spondyloarthritis (SpA).
In the pooled cohort of participants in the IDEAL, TNT, and CARDS trials, 50 had ankylosing spondylitis (AS), 36 had psoriatic arthritis (PsA), and 21,641 did not have AS or PsA (non-SpA). We compared lipid...
The associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented.
To evaluate the relative strength of the associations of LDL-C, non-HDL-C, and...
Carriers of the KIF6 719Arg variant may be at increased risk for CVD and may benefit more from statin therapy, in terms of CVD risk reduction, than noncarriers. Our objective was to investigate whether carriers of the KIF6 719Arg genetic variant (rs20455) are at increased cardiovascular risk and obtain more benefit from high-dose statin therapy tha...
Background: Carriers of the KIF6 Trp719Arg genetic variant are at increased risk for cardiovascular disease (CVD). It has been suggested that CVD risk in carriers of the KIF6 variant can be significantly reduced by statin therapy. We hypothesized that carriers of the KIF6 variant obtain more benefit from high-dose statin therapy than do noncarriers...
The Treating to New Targets (TNT) study has recently provided evidence that reduction in LDL-C levels below 2·6 mmol L⁻¹ lowers the risk of cerebrovascular events by an additional 20% to 25%, thereby confirming the value of statin therapy in preventing transient ischaemic attacks and stroke. Despite the protective effects of statin therapy, the epi...
In patients with coronary artery disease (CAD), a J-curve relationship has been reported between blood pressure (BP) and future cardiovascular events. However, this is controversial. The purpose of the study was to determine the relationship between on-treatment BP and cardiovascular outcomes in patients with CAD.
We evaluated 10 001 patients with...
The aim of this study was to investigate the relationship between lipid and nonlipid biomarker levels achieved during statin therapy and the incidence of major cardiovascular events (MCVEs) in patients with stable coronary heart disease (CHD).
Several plasma nonlipid biomarkers have been shown to predict MCVEs in population studies.
This is a neste...
Analyses of randomized clinical trials are usually restricted to examination of time to first event. However, because many patients have multiple events, this approach precludes much potentially useful clinical and economic data. To assess the effect on overall disease burden in the Treating to New Targets (TNT) study, we evaluated the effect of tr...
We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg/day with moderate-dose statin therapy (simvastatin 20...
The Treating to New Targets (TNT) study demonstrated that intensive atorvastatin therapy to achieve low-density lipoprotein cholesterol concentrations well below recommended target levels provides an incremental clinical benefit in patients with stable coronary artery disease. This post hoc analysis of the TNT study was conducted to investigate whe...
In the Treating to New Targets (TNT) study, 10,001 patients with stable CHD and LDL-C levels <130 mg/dL (3.4 mmol/L) were randomized to double-blind therapy with either atorvastatin 10 or 80 mg/day and were followed for a median of 4.9 years. The primary endpoint was an occurrence of a first major cardiovascular event, defined as CHD death, nonfata...
Low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL ch...
The aim of this post hoc analysis from the TNT (Treating to New Targets) trial is to determine whether patients with previous coronary artery bypass grafting (CABG) surgery achieved clinical benefit from intensive low-density lipoprotein (LDL)-cholesterol lowering.
The development and progression of atherosclerosis is accelerated in coronary venous...
This post-hoc analysis of the Treating to New Targets (TNT) study evaluated the joint effects of managing low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) on cardiovascular outcomes. Patients (N=9739) with clinically evident, stable coronary heart disease (CHD) were randomized to atorvastatin 10 or 80 mg/d. The primary...
High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol.
A post hoc analysis of the recently completed Treating to New Targets (TNT) study assessed the predictive value of...
High-dose statin therapy has been demonstrated to provide incremental benefit when low-density lipoprotein (LDL) cholesterol concentrations are lowered well below recommended target levels. This secondary analysis of the Treating to New Targets (TNT) study was conducted to investigate whether the attainment of very low LDL cholesterol levels was as...
In the last 2 decades, the benefit of lowering low-density lipoprotein (LDL) cholesterol has been shown beyond reasonable doubt (1,2). Both death and disability from the progress of coronary artery disease can be delayed, and there is recent evidence showing that disabling stroke also can be avoided (3). Few issues in modern medicine have been so t...
Many epidemiologic studies and clinical trials have demonstrated the linear relation between elevated serum levels of low-density lipoprotein (LDL) cholesterol and the risk for coronary heart disease. Conversely, for each 1% reduction in LDL cholesterol in clinical trials, there is a corresponding 1% reduction in coronary heart disease risk. Althou...
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We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl.
Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low c...
Background:
Despite the prognostic value of metabolic syndrome for predicting cardiovascular events, few trials have investigated the effects of statin therapy on cardiovascular morbidity and mortality in patients with the metabolic syndrome. Our post hoc analysis of the Treating to New Targets (TNT) study assessed whether intensive lowering of lo...
Coronary heart disease (CHD) remains an urgent and leading threat to women's health and well-being. Clinical trials have demonstrated a clear cut benefit of low density lipoprotein cholesterol (LDL-C) lowering in both women as well as men with coronary disease. While the case for primary prevention of CHD with LDL-C lowering is less secure in both...
The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastat...
Recent clinical trials have confirmed the value of intervention on major risk factors, particularly hypertension and hyperlipidemia, in preventing the progression and clinical sequelae of atherosclerosis. Less is known about the prevalence and impact of atherosclerosis risk factors in minorities. A review of recent literature reporting the prevalen...
Early hydroxymethylglutaryl-CoA reductase inhibitor (statin) trials provided the first evidence of the benefits of statin therapy in secondary prevention of coronary heart disease (CHD). Outcomes data from more recent trials involving atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin, have since expanded the patient population sho...
With improvements in diet and health care over the last several decades, the elderly have become the fastest-growing segment of the U.S. population. Along with this progress, however, has come increasing morbidity, much of which is attributable to cardiovascular disease, and which is burdensome both to patients and to the health-care system. New me...
Recent trials indicate intensive lipid-lowering therapy beyond traditionally recommended levels in patients with acute coronary syndromes provides increased benefit with respect to cardiovascular endpoints compared with traditional lipid-lowering therapy in such patients (N Engl J Med 2004;50:1495-504, and J Am Col Cardiology 2004;44:1772-9). This...
Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coro...
Evolution of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines for lipid lowering reflects a movement toward global risk assessment, including improved identification of risk in individuals without established coronary heart disease (CHD), and toward more aggressive lipid-lowering targets to reduce CHD risk. T...
Elsewhere in this issue, Dr. Ballantyne and his colleagues present a meta-analysis of the clinical endpoint trials of fluvastatin, one of the cholesterol lowering hydroxymethyl coenzyme A reductase inhibitors (statins) that have become so widely used in the last decade. The total number of patients studied in randomized clinical trials of fluvastat...
Recent clinical trials of statins have clearly demonstrated the benefit of statin therapy in preventing both coronary and cerebral vascular events. These benefits have been demonstrated to be present without reference to older age, sex, or comorbid conditions, including hypertension and diabetes. Future trials will test the value of more aggressive...
Women and men are both susceptible to coronary artery disease (CAD). The predictors or risk factors of CAD are qualitatively
identical, although low-density lipoprotein is less of a predictor, and high-density lipoprotein and triglycerides are more
predictive in women. Diabetes is also a stronger predictor of CAD in women. Lowering of low-density l...
The association between elevated serum cholesterol levels and cardiovascular risk was established several decades ago by studies such as the Framingham study and the Multiple Risk Factor Intervention Trial (MRFIT). Both primary and secondary prevention trials of cholesterol lowering, using HMG-CoA reductase inhibitors, have demonstrated clear benef...
The association between elevated serum cholesterol levels and cardiovascular risk was established several decades ago by studies such as the Framingham study and the Multiple Risk Factor Intervention Trial (MRFIT). Both primary and secondary prevention trials of cholesterol lowering, using HMG-CoA reductase inhibitors, have demonstrated clear benef...
Atherosclerosis was relatively uncommon 100 years ago, when researchers first established its link to elevated cholesterol. As the twentieth century progressed, however, factors such as high-fat diets, sedentary lifestyles, cigarette smoking, and urbanization combined to increase the prevalence of both hypercholesterolemia and coronary heart diseas...
Emerging evidence suggests that cholesterol lowering in older patients is beneficial in reducing both morbidity and mortality resulting from coronary atherosclerosis, and therefore, age should not be an excluding factor when considering lipid intervention. However, results from ongoing trials are needed to more clearly define which patients should...
Until the recent introduction of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), the potential effect of cholesterol lowering on the prevention of clinical manifestations of coronary disease was a matter of debate. In trials conducted before the introduction of statins, cholesterol levels were lowered, on average, by only...
Life expectancy, at an historical high in the wealthiest nations, may begin to take a downward trend unless medical and health care breakthroughs intervene. On the African continent, acquired immune deficiency syndrome continues to devastate large segments of the population, while in the European Union, the United States, and other developed countr...
Risk factors associated with the progression of coronary disease are the same in women and men, although there are some quantitative differences. Diabetic women, for example, are exquisitely sensitive to the development of atherosclerosis. There is no clinical trial devoted to the study of cholesterol lowering in women. A meta-analysis of recent st...
Risk factors associated with the progression of coronary disease are the same in women and men, although there are some quantitative differences. Diabetic women, for example, are exquisitely sensitive to the development of atherosclerosis. There is no clinical trial devoted to the study of cholesterol lowering in women. A meta-analysis of recent st...
Elevated triglycerides and low high-density lipoprotein (HDL) levels are more important coronary risk factors in women, and elevated low-density lipoprotein (LDL) levels less important in women, than men. There is clear-cut evidence in clinical trials that the benefit of cholesterol lowering in women and men is virtually identical.
Modifiers of lip...
