Current Atherosclerosis Reports 11/2010; 13(1):4-8. · 2.66 Impact Factor
Current Atherosclerosis Reports 11/2010; 13(1):1-3. · 2.66 Impact Factor
Current Atherosclerosis Reports 01/2010; 12(1):8-10. · 2.66 Impact Factor
Current Atherosclerosis Reports 01/2010; 12(1):1-4. · 2.66 Impact Factor
Current Atherosclerosis Reports 01/2010; 12(1):5-7. · 2.66 Impact Factor
Current Atherosclerosis Reports 09/2008; 10(4):273-6. · 2.66 Impact Factor
ABSTRACT: Cardiovascular disease remains the leading cause of death in both men and women in the United States. Treating elevated low-density lipoprotein (LDL) cholesterol has been shown to be very effective in reducing the rate of coronary heart disease (CHD) in primary prevention trials; however, the data are not as robust for treating individuals categorized at either lower risk for CHD or with below-average LDL cholesterol levels. The next frontier for investigation will include strategies to determine who in these lower risk categories should be treated with statins. The growing epidemics of obesity, diabetes, and metabolic syndrome also loom as major problems that need to be incorporated into any strategy that focuses on the prevention of cardiovascular disease. In individuals with multiple cardiovascular risk factors, combination therapies tailored to address each individual's risk profile need to be considered to best decrease the likelihood of their first coronary event.
Current Atherosclerosis Reports 10/2006; 8(5):390-6. · 2.66 Impact Factor
ABSTRACT: The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) first reported its results in 1998, before the 2001 publication of the National Cholesterol Education Program-Adult Treatment Panel III guidelines (NCEP-ATP III) and 2004 update. Our objective was to investigate the impact of these guidelines on the AFCAPS/TexCAPS cohort. The main outcome measures were the event rates of first acute major coronary events (AMCEs), which were reduced 39% by lovastatin (95% confidence interval [CI] 21% to 53%, p <0.001) in the 65% of the cohort eligible for drug therapy and by 34% (95% CI -9% to 60%, p = 0.108) in the remaining 35% for whom drug therapy was considered optional. The evaluation of other guideline components included a 44% (95% CI 27% to 58%, p <0.001) reduction in AMCEs in subjects with baseline high-density lipoprotein cholesterol <40 mg/dl and a 41% (95% CI 19% to 57%) reduction in AMCEs in subjects with the metabolic syndrome. In the recent update, patients who had a moderately high risk of coronary heart disease and a baseline low-density lipoprotein cholesterol level of 100 to 130 mg/dl could be considered for therapy with a medication to lower the low-density lipoprotein cholesterol level to <100 mg/dl. A total of 334 subjects (5.1%) were in this group, in whom lovastatin reduced the risk of AMCEs by 68% (95% CI 12% to 88%, p = 0.027). However, 21% of the AMCEs were missed by the guidelines. Metabolic syndrome was noted in 48% of these subjects and may help define those in whom treatment with a medication is now considered optional. In conclusion, the ability of the ATP III guidelines and its update has markedly improved our ability to define coronary heart disease risk; however, other components of the guidelines, such as non-high-density lipoprotein cholesterol and the optional low-density lipoprotein cholesterol target goal of <100 mg/dl, still require additional evaluation.
The American Journal of Cardiology 12/2005; 96(12):1674-80. · 3.37 Impact Factor
Current Atherosclerosis Reports 03/2005; 7(1):8. · 2.66 Impact Factor
Current Atherosclerosis Reports 03/2005; 7(1):7-8. · 2.66 Impact Factor
Current Atherosclerosis Reports 03/2005; 7(1):9. · 2.66 Impact Factor
Current Atherosclerosis Reports 03/2005; 7(1):9-10. · 2.66 Impact Factor
ABSTRACT: The incidence of coronary heart disease in women rises sharply in the years following menopause, and prescribing of hormone replacement therapy in the belief that it might compensate for the loss of estrogen-mediated cardioprotection is widespread. However, controlled trials have failed to show a beneficial effect of hormone replacement therapy on the incidence of coronary events, and recent evidence suggests that hormone replacement therapy may even have a deleterious effect on primary coronary heart disease prevention. Statins are recommended as first-line treatment for lowering low-density lipoprotein cholesterol levels in women and are extremely valuable in reducing coronary heart disease risk in this group. An awareness of the benefits of appropriate statin treatment, and evidence showing that they can be safely added to hormone replacement therapy prescribed for the relief of menopausal symptoms and osteoporosis, provides the opportunity to optimize clinical outcomes for coronary heart disease among the large and expanding population of postmenopausal women.
Preventive Cardiology 02/2004; 7(3):131-6.
ABSTRACT: The metabolic syndrome, which is a set of lipid and nonlipid risk factors of metabolic origin linked with insulin resistance, is believed to be associated with an elevated risk for cardiovascular disease, but few have studied this association in prospective long-term cardiovascular outcomes trials. Placebo data from the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) were used post hoc to estimate the long-term relative risk of major coronary events (MCEs) associated with the metabolic syndrome, after excluding diabetes mellitus. In 4S and AFCAPS/TexCAPS, respectively, placebo-treated patients with the metabolic syndrome were 1.5 (95% confidence interval 1.2 to 1.8) and 1.4 (95% confidence interval 1.04 to 1.9) times more likely to have MCEs than those without it. Of the components of the metabolic syndrome, low high-density lipoprotein levels were associated with elevated risk of MCEs in both studies, whereas high triglycerides in 4S and elevated blood pressure and obesity in AFCAPS/TexCAPS were associated with significantly increased relative risk. Patients with the metabolic syndrome showed increased risk of MCEs irrespective of their Framingham-calculated 10-year risk score category (>20% vs </=20%). These data demonstrate that the metabolic syndrome is associated with increased risk of MCEs in both hypercholesterolemic patients with coronary heart disease in 4S and in those with low high-density lipoprotein cholesterol but without coronary heart disease in AFCAPS/TexCAPS. It appears that the metabolic syndrome is associated with risk that is not entirely accounted for by traditional risk scoring paradigms.
The American Journal of Cardiology 02/2004; 93(2):136-41. · 3.37 Impact Factor
ABSTRACT: Elevated homocysteine levels are associated with increased coronary risk, and it has been suggested that homocysteine screening may provide a method to identify high-risk patients for aggressive primary prevention.
Homocysteine was measured at baseline and after 1 year among 5569 participants in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), a randomized trial of lovastatin in the primary prevention of acute coronary events. The effects of homocysteine, LDL cholesterol, and lovastatin on risk were assessed over 5.2 years of trial follow-up. Median baseline homocysteine levels were significantly higher among study participants who subsequently had acute coronary events compared with those who did not (12.1 versus 10.9 micro;mol/L, P<0.001). The relative risks of future events from lowest (referent) to highest quartile of homocysteine were 1.0, 1.6, 1.6, and 2.2 (P<0.001). These effects were similar among those allocated to lovastatin and those allocated to placebo and were modestly attenuated after adjustment for other traditional risk factors. As predicted, the subgroup of participants with elevated LDL cholesterol and elevated homocysteine levels were at high risk and benefited greatly from statin therapy (relative risk, 0.46; 95% CI, 0.29 to 0.75; number needed to treat=26). However, in contrast to findings in this trial for C-reactive protein, homocysteine evaluation did not help to define low LDL subgroups with different responses to lovastatin therapy.
Although homocysteine predicted future coronary events in AFCAPS/TexCAPS, we found little evidence that homocysteine evaluation provided an improved method to target statin therapy among those with low-to-normal LDL cholesterol levels.
Circulation 05/2002; 105(15):1776-9. · 14.74 Impact Factor
ABSTRACT: The development of therapies for the control of atherosclerosis is an important example of the drug discovery process. Findings from population studies initiated 4 decades ago have been gradually translated to today's therapies, the most effective of which are the statins. Driven by an increased understanding of the atherosclerotic process and shortfalls of current treatments, the development of therapies for cholesterol control continues, with new agents in the pipeline promising therapeutic benefits over existing treatments. The advent of new statins such as rosuvastatin and pitavastatin, with improved efficacy for reducing cholesterol and the ability to positively affect other disease risk factors, may exploit the potential for improvement of current treatments.
American Journal of Therapeutics 10(4):275-81. · 1.49 Impact Factor
ABSTRACT: This study presents the long-term safety data from AFCAPS/TexCAPS, the first primary prevention trial to demonstrate that men and women with average levels of low-density lipoprotein cholesterol (LDL-C) and below average levels of high-density lipoprotein cholesterol (HDL-C) can significantly benefit from long-term treatment to lower LDL-C; lovastatin 20 to 40 mg/day reduced the risk of a first acute major coronary event (fatal or nonfatal myocardial infarction, unstable angina, or sudden death) by 37% (p = 0.00008). This double-blind randomized, placebo-controlled trial, in 6,605 generally healthy middle-aged and older men and women, had prespecified end point and cancer analyses. All analyses were intention-to-treat. Safety monitoring included history, physical examination, and laboratory studies (including hepatic transaminases and creatine phosphokinase [CPK]). All participants, even those who discontinued treatment, were contacted annually for vital status, cardiovascular events, and cancer history. After an average of 5.2 years of follow-up, there were 157 deaths (80 receiving lovastatin and 77 receiving placebo; relative risk [RR] 1.04; 95% confidence interval [CI] 0.76 to 1.42; p = 0.82); of which 115 were noncardiovascular (RR 1.21; CI 0.84 to 1.74; p = 0.31), and of these, 82 were due to cancer (RR 1.41; CI 0.91 to 2.19; p = 0.13). There were no significant differences between treatment groups in overall cancer rates, discontinuations for noncardiovascular adverse experiences, or clinically important elevations of hepatic transaminases or CPK. Among those who used cytochrome P450 isoform (CYP3A4) inhibitors, there were no treatment group differences in the frequency of clinically important muscle-related adverse events. Treatment with lovastatin 20 to 40 mg daily for primary prevention of coronary heart disease was well tolerated and reduced the risk of first acute coronary events without increasing the risk of either noncardiovascular mortality or cancer.
The American Journal of Cardiology.
Although cholesterol-reducing treatment has been shown to reduce fatal
and nonfatal coronary disease in patients with coronary heart disease (CHD),
it is unknown whether benefit from the reduction of low-density lipoprotein
cholesterol (LDL-C) in patients without CHD extends to individuals with average
serum cholesterol levels, women, and older persons.Objective.—
To compare lovastatin with placebo for prevention of the first acute
major coronary event in men and women without clinically evident atherosclerotic
cardiovascular disease with average total cholesterol (TC) and LDL-C levels
and below-average high-density lipoprotein cholesterol (HDL-C) levels.Design.—
A randomized, double-blind, placebo-controlled trial.Setting.—
Outpatient clinics in Texas.Participants.—
A total of 5608 men and 997 women with average TC and LDL-C and below-average
HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort
without cardiovascular disease from the National Health and Nutrition Examination
Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 
mg/dL) (51st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150
 mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L
(36  mg/dL) for men and 1.03 (0.14) mmol/L (40  mg/dL) for women (25th
and 16th percentiles, respectively), and median (SD) triglyceride levels were
1.78 (0.86) mmol/L (158  mg/dL) (63rd percentile).Intervention.—
Lovastatin (20-40 mg daily) or placebo in addition to a low–saturated
fat, low-cholesterol diet.Main Outcome Measures.—
First acute major coronary event defined as fatal or nonfatal myocardial
infarction, unstable angina, or sudden cardiac death.Results.—
After an average follow-up of 5.2 years, lovastatin reduced the incidence
of first acute major coronary events (183 vs 116 first events; relative risk
[RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001),
myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI,
0.43-0.83; P=.002), unstable angina (87 vs 60 first
unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02),
coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95%
CI, 0.52-0.85; P=.001), coronary events (215 vs 163
coronary events; RR, 0.75; 95% CI, 0.61-0.92; P=.006),
and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95%
CI, 0.62-0.91; P=.003). Lovastatin (20-40 mg daily)
reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6%
to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in
safety parameters between treatment groups.Conclusions.—
Lovastatin reduces the risk for the first acute major coronary event
in men and women with average TC and LDL-C levels and below-average HDL-C
levels. These findings support the inclusion of HDL-C in risk-factor assessment,
confirm the benefit of LDL-C reduction to a target goal, and suggest the need
for reassessment of the National Cholesterol Education Program guidelines
regarding pharmacological intervention.
Figures in this Article
EPIDEMIOLOGICAL observations have demonstrated consistently a strong
positive, continuous, independent, graded relation between plasma total cholesterol
(TC) and the incidence of coronary heart disease (CHD). This relation covers
a wide range of cholesterol concentrations, including those considered normal
or mildly elevated.1- 3
In the Multiple Risk Factor Intervention Trial follow-up of screened men,
69% of deaths from CHD in the first 6 years of follow-up occurred in subjects
with TC values between 4.71 and 6.83 mmol/L (182-264 mg/dL).4
In the first 16 years of the Framingham Heart Study, 40% of participants who
developed a myocardial infarction had a TC level between 5.17 and 6.47 mmol/L
Large end point studies have demonstrated conclusively that effective
cholesterol-lowering treatment can substantially reduce myocardial infarction
and other coronary events. In the Scandinavian Simvastatin Survival Study
the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin
reduced total mortality in patients with CHD by 30% because of a 42% reduction
in deaths from CHD.6 Subsequently, pravastatin
was shown to reduce fatal and nonfatal coronary events in patients with7 and without8 CHD. However,
it is unknown whether benefit from reduction of low-density lipoprotein cholesterol
(LDL-C) in patients without CHD (primary prevention) extends to individuals
with average serum cholesterol levels, women, and older persons.
The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)
targeted a cohort of generally healthy middle-aged and older men and women
with average TC and LDL-C levels and with below-average high-density lipoprotein
cholesterol (HDL-C) levels. The primary end point analysis was the incidence
of first acute major coronary events, defined as fatal or nonfatal myocardial
infarction, unstable angina, or sudden cardiac death. The inclusion of unstable
angina was a unique feature of this study, and its inclusion as a primary
end point reflects the increasing frequency of unstable angina as the initial
presentation of CHD in the United States.9
JAMA The Journal of the American Medical Association 279(20):1615-1622. · 30.03 Impact Factor