Multiple Coronary Heart Disease Risk Factors Research Articles

Nonalcoholic Fatty Liver Disease and Cardiovascular Disease.

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Hypothyroidism and Moderate Subclinical Hypothyroidism Are Associated with Increased All-Cause Mortality Independent of Coronary Heart Disease Risk Factors: A PreCIS Database Study

Thyroid hormones have profound effect on the heart and peripheral vasculature. Hypothyroidism is associated with an increase in a number of coronary heart disease (CHD) risk factors including dyslipidemia, hypertension, and elevated levels of homocysteine. Our objective was to assess the effects of hypothyroidism (thyroid-stimulating hormone [TSH]: >10 μ U/mL), moderate subclinical hypothyroidism (SCH; TSH: 6.1-10 μ U/mL), and mild SCH (TSH: 3.1-6.0 μ U/mL) on cardiovascular risk factors, CHD prevalence, and all-cause mortality in patients at high risk for CHD seen in a preventive cardiology clinic. All patients seen in the Cleveland Clinic Preventive Cardiology clinic have demographic and laboratory tests including TSH and multiple CHD risk factors obtained at the baseline visit. All data are entered into a database (called PreCIS). The social security death index is queried monthly to determine all-cause mortality. Several CHD risk factors including age, male gender, systolic blood pressure, triglycerides, and fibrinogen were more common in hypothyroid patients. Prevalence of CHD was more common in hypothyroid and moderate SCH patients. All-cause mortality was higher in hypothyroid and moderate SCH patients, but not in mild SCH patients. Higher mortality in these groups was observed in both genders, patients under 65 years of age, and patients not on thyroid replacement therapy, but was not observed in patients over 65 years of age. Hypothyroidism and moderate, but not mild, SCH are associated with increased CHD prevalence and all-cause mortality. These observations suggest patients with moderate, but not mild, SCH and patients at high risk for CHD should be treated with thyroid replacement therapy.

Insights Gained from 20 Years of Soy Research ,

Soyfoods have long been recognized for their high-protein and low-saturated fat content, but over the past 20 y an impressive amount of soy-related research has evaluated the role of these foods in reducing chronic disease risk. Much of this research has been undertaken because the soybean is essentially a unique dietary source of isoflavones, a group of chemicals classified as phytoestrogens. The estrogen-like properties of isoflavones have also raised concern, however, that soyfoods might exert adverse effects in some individuals. There is intriguing animal and epidemiologic evidence indicating that modest amounts of soy consumed during childhood and/or adolescence reduces breast cancer risk. Evidence also suggests that soy reduces prostate cancer risk and inhibits prostate tumor metastasis, but additional clinical support for the chemopreventive effects of soyfoods is needed. Soy protein is modestly hypocholesterolemic and there is suggestive epidemiologic evidence that soyfoods lower risk of coronary heart disease (CHD) independent of effects on cholesterol. In clinical studies, soy favorably affects multiple CHD risk factors; however, with the exception of improved endothelial function, the data are too limited and/or inconsistent to allow definitive conclusions to be made. In regard to bone health, although recent clinical data have not supported the skeletal benefits of isoflavones, 2 large prospective epidemiologic studies found soy intake is associated with marked reductions in fracture risk. Soybean isoflavones also modestly alleviate hot flashes in menopausal women. Finally, other than allergic reactions, there is almost no credible evidence to suggest traditional soyfoods exert clinically relevant adverse effects in healthy individuals when consumed in amounts consistent with Asian intake.

Quantitative effects on cardiovascular risk factors and coronary heart disease risk of replacing partially hydrogenated vegetable oils with other fats and oils

Reduced consumption of trans-fatty acids (TFA) is desirable to lower coronary heart disease (CHD) risk. In practice, partially hydrogenated vegetable oils (PHVO) that contain both TFAs and other fatty acids are the unit of replacement and could be replaced with diverse alternative fats and oils. We performed quantitative estimates of CHD effects if a person's PHVO consumption were to be replaced with alternative fats and oils based on (1) randomized dietary trials and (2) prospective observational studies. We performed meta-analyses of (1) the effects of TFAs on blood lipids and lipoproteins in controlled dietary trials and (2) associations of habitual TFA consumption with CHD outcomes in prospective cohort studies. On the basis of these results and corresponding findings for saturated fatty acids (SFA), cis-monounsaturated fatty acids (MUFA) and cis-polyunsaturated fatty acids (PUFA), we calculated the effects on CHD risk for replacing 7.5% of energy from three different PHVO formulations (containing 20, 35 or 45% TFAs) with butter, lard, palm or vegetable oils. In controlled trials, each 1% energy replacement of TFAs with SFAs, MUFAs or PUFAs, respectively, decreased the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio by 0.31, 0.54 and 0.67; the apolipoprotein (Apo)-B/ApoAI ratio by 0.007, 0.010 and 0.011; and lipoprotein (Lp)(a) by 3.76, 1.39 and 1.11 mg/l (P<0.05 for each). We also included possible effects on C-reactive protein (CRP) of TFAs vs other fats from one trial. On the basis of these risk factor changes in controlled trials, CHD risk would be variably decreased by different fats and oils replacing 7.5% of energy from 20% TFA PHVO (CHD risk reduction: -2.7% (butter) to -9.9% (canola)); 35% TFA PHVO (-11.9% (butter) to -16.0% (canola)); or 45% TFA PHVO (-17.6% (butter) to -19.8% (canola)). In prospective cohort studies, each 2% energy replacement of TFAs with SFAs, MUFAs or PUFAs would lower CHD risk by 17% (95% confidence interval (CI)=7-25%), 21% (95% CI=12-30%) or 24% (95% CI=15-33%), respectively. On the basis of these associations in observational studies, CHD risk would be variably decreased by different fats and oils replacing 7.5% of energy from 20% TFA PHVO (CHD risk reduction: +0.5% (butter) to -21.8% (soybean)); 35% TFA PHVO (-14.4% (butter) to -33.4% (soybean)); or 45% TFA PHVO (-22.4% (butter) to -39.6% (soybean)). The demonstrated effects on TC/HDL-C, ApoB/ApoAI, Lp(a), and CRP in randomized feeding trials together accounted for approximately 65-80% and approximately 50% of the estimated risk reduction for replacing PHVO with animal fats and vegetable oils, respectively, that would be calculated from prospective cohort studies. Effects on CHD risk of removing PHVO from a person's diet vary depending on the TFA content of the PHVO and the fatty acid composition of the replacement fat or oil, with direct implications for reformulation of individual food products. Accounting for the summed effects of TFAs on multiple CHD risk factors provides more accurate estimates of potential risk reduction than considering each risk factor in isolation, and approaches the estimated risk reduction derived from prospective cohort studies.

Depressive behavior and coronary artery atherogenesis in adult female cynomolgus monkeys.

To examine depressive behavior and early coronary artery atherogenesis in 36 socially housed female cynomolgus monkeys, an established model of atherogenesis and depression. Coronary heart disease (CHD) is caused by coronary artery atherosclerosis (CAA) and its sequelae which develop over a period of decades. Thus, in prospective studies of depression and CHD, CAA was likely present at baseline in most subjects who experienced cardiac events. Little is known about the relationship between depression and CAA. The monkeys were free of atherosclerosis before being fed a diet containing moderate amounts of fat and cholesterol for 52 months. Depressed behavior and activity levels recorded in weekly 15-minute focal samples, telemetered 24-hour heart rate, plasma total (TPC) and high-density lipoprotein cholesterol (HDLC), luteal phase serum progesterone concentrations, basal cortisol, cortisol response to corticotrophin-releasing hormone (CRH), and CAA extent were assessed. Time spent in depressed behavior over 4 years was significantly associated with early CAA (r = .73, p < .001), as were activity level, 24-hour heart rate, TPC, HDLC, cortisol response to CRH, and mean peak progesterone (all p < or = 0.05). Depressed females had four times the CAA compared with nondepressed females. Depression in primates is associated with perturbations in multiple CHD risk factors and accelerated early atherogenesis. These data are consistent with the hypotheses that depression and CAA both stem from a common mechanism and that depression may cause CAA.

Reduced Incidence of Invasive Breast Cancer With Raloxifene Among Women at Increased Coronary Risk

In the Raloxifene Use for The Heart trial, 10 101 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors were randomly assigned to 60 mg/d raloxifene or to placebo and followed for a median of 5.6 years. Raloxifene, a selective estrogen receptor modulator, was found to reduce the risk of invasive breast cancer and vertebral fractures but not the risk of cardiovascular events. Here, we provide further details about breast cancer incidence by tumor characteristics, duration of treatment, and subgroup. Reported breast cancer was adjudicated by an independent committee based on medical records and pathology reports. The primary analyses used Cox proportional hazards models with time to first breast cancer as the outcome. Subgroup effects were analyzed using similar models with terms for treatment by subgroup. All statistical tests were two-sided. As previously reported, raloxifene reduced the incidence of invasive breast cancer by 44% (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.38 to 0.83; absolute risk reduction = 1.2 invasive breast cancers per 1000 women treated for 1 year). The lower incidence of invasive breast cancer reflected a 55% lower incidence of invasive estrogen receptor (ER)-positive tumors (HR = 0.45; 95% CI = 0.28 to 0.72). However, raloxifene treatment did not reduce the incidence of noninvasive breast cancer or of invasive ER-negative breast cancer. The reduced incidence of invasive breast cancer was similar across subgroups, including those defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and 5-year estimated risk of invasive breast cancer. Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman's baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers. These results confirm those of the Multiple Outcomes of Raloxifene Evaluation, a previous randomized trial among women with osteoporosis.

Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults

Coronary heart disease (CHD) risk factors increase with age and body mass index (BMI; in kg/m2). However, whether lifestyle intervention ameliorates metabolic CHD risk factors in obese older adults is unknown. The objective was to determine whether lifestyle intervention improves metabolic CHD risk factors in obese older adults. A 6-mo outpatient randomized controlled trial was conducted in obese (BMI >or= 30) older (>or=65 y) adults randomly assigned to diet and exercise therapy (treatment group; n = 17) or no therapy (control group; n = 10). The main outcomes were CHD risk factors. Body weight decreased by 8.4% (8.2 kg) in the treatment group; weight did not change significantly (0.7 kg) in the control group (P < 0.001 between groups). Changes between the control and treatment groups, respectively, in waist circumference (1 and -10 cm), plasma glucose (4 and -4 mg/dL), serum triacylglycerols (0 and -45 mg/dL), and systolic (-2 and -10 mm Hg) and diastolic (0 and -8 mm Hg) blood pressure were different (P < 0.05 for all). The number of subjects with the metabolic syndrome decreased by 59% in the treatment group but did not change significantly in the control group (P < 0.05). Serum free fatty acids increased by 10 micromol/L in the control group and decreased by 99 micromol/L in the treatment group (P < 0.05). Changes between the control and treatment groups, respectively, in C-reactive protein (0.8 and -2.5 mg/L) and interleukin 6 (1.6 and -2.4 pg/mL) were different (P < 0.05 for both). Lifestyle intervention decreases multiple metabolic CHD risk factors simultaneously in obese older adults.

Effect of Short‐Term Pritikin Diet Therapy on the Metabolic Syndrome

The Pritikin Program (Aventura, FL) involves the use of a very-low-fat, low-sodium, high-fiber diet and exercise to decrease the risk of coronary heart disease (CHD). This study evaluated the effect of short-term Pritikin therapy on the metabolic risk factors for CHD in patients with the metabolic syndrome. Sixty-seven subjects who had the metabolic syndrome and attended the Pritikin Longevity Center & Spa for 12-15 days were studied. Short-term Pritikin therapy improved most CHD risk factors: body mass index decreased by 3% (P<.001); systolic and diastolic blood pressure, and serum glucose and low-density lipoprotein cholesterol concentrations decreased by 10%-15% (P<.001); serum triglyceride concentration decreased by 36% (P<.001); and 37% of subjects no longer met National Cholesterol Education Program criteria for the metabolic syndrome. Serum high-density lipoprotein cholesterol, however, decreased by 3% (P<.05). These data demonstrate that brief treatment with a very-low-fat, low-sodium, high-fiber diet and regular exercise simultaneously improves multiple CHD risk factors in patients with the metabolic syndrome.

Effects of Raloxifene on Cardiovascular Events and Breast Cancer in Postmenopausal Women

The effect of raloxifene, a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer is not established. We randomly assigned 10,101 postmenopausal women (mean age, 67.5 years) with CHD or multiple risk factors for CHD to 60 mg of raloxifene daily or placebo and followed them for a median of 5.6 years. The two primary outcomes were coronary events (i.e., death from coronary causes, myocardial infarction, or hospitalization for an acute coronary syndrome) and invasive breast cancer. As compared with placebo, raloxifene had no significant effect on the risk of primary coronary events (533 vs. 553 events; hazard ratio, 0.95; 95 percent confidence interval, 0.84 to 1.07), and it reduced the risk of invasive breast cancer (40 vs. 70 events; hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for one year); the benefit was primarily due to a reduced risk of estrogen-receptor-positive invasive breast cancers. There was no significant difference in the rates of death from any cause or total stroke according to group assignment, but raloxifene was associated with an increased risk of fatal stroke (59 vs. 39 events; hazard ratio, 1.49; 95 percent confidence interval, 1.00 to 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous thromboembolism (103 vs. 71 events; hazard ratio, 1.44; 95 percent confidence interval, 1.06 to 1.95; absolute risk increase, 1.2 per 1000 woman-years). Raloxifene reduced the risk of clinical vertebral fractures (64 vs. 97 events; hazard ratio, 0.65; 95 percent confidence interval, 0.47 to 0.89; absolute risk reduction, 1.3 per 1000). Raloxifene did not significantly affect the risk of CHD. The benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke. (ClinicalTrials.gov number, NCT00190593 [ClinicalTrials.gov].).

Target value of intraabdominal fat area for improving coronary heart disease risk factors.

The goal of this study was to determine an intraabdominal fat (IF) area target value for improving coronary heart disease (CHD) risk factors in response to weight reduction. Subjects were 279 obese Japanese women, 21 to 66 years old, who were divided into diet-alone and diet-plus-exercise groups and participated in a 14-week weight reduction program. The IF area was measured by computerized tomography scans. Systolic blood pressure > or = 140 mm Hg, diastolic blood pressure > or = 90 mm Hg, total cholesterol > or = 5.70 mM, triglycerides > or = 1.70 mM, and fasting plasma glucose > or = 6.99 mM were defined as CHD risk factors. The best trade-off between sensitivity (probability of correctly detecting true positive) and specificity (probability of correctly detecting true negative) was found at 100 cm2 pretreatment in combined data of the two groups. At posttreatment, although a slight difference was found in the target value between the treatment groups (60 cm2 for diet alone and 50 cm2 for diet plus exercise), the combined data showed that the best trade-off occurred at 60 cm2 (sensitivity and specificity were 0.55 and 0.63, respectively). The percentage of subjects having no CHD risk factors was significantly lower in the group that had large IF areas (> or = 60 cm2) (46%) compared with the group that had normal IF areas (<60 cm2) (65%). However, the percentage of subjects having multiple CHD risk factors was significantly greater in the group that had large IF areas (16%) compared with the group with normal IF areas (7%) at posttreatment. Our longitudinal data suggest that obese Japanese women should reduce their IF areas to < 60 cm2 through weight reduction to improve CHD risk factors independent of treatment.

Multiple lipoprotein abnormalities associated with insulin resistance in healthy volunteers are identified by the vertical auto profile-II methodology.

The lipoprotein abnormalities first associated with insulin resistance (IR) and compensatory hyperinsulinemia were high plasma triglyceride (TG) and low HDL-cholesterol (HDL-C) concentrations (1)(2). It is now known that the characteristic IR-associated dyslipidemia also includes a shift to smaller, denser LDL particles (pattern B), enhanced postprandial lipemia, and decreased concentration of the more buoyant HDL particle, HDL2 (3)(4)(5). Recently, the IR-associated lipoprotein abnormalities that increase risk of coronary heart disease (CHD) have continued to expand. In addition to high plasma TG and low HDL-C concentrations (6)(7), at least three classes of TG-rich lipoproteins are both atherogenic and associated with increased CHD risk, including intermediate density lipoprotein (IDL; a TG-rich remnant product derived from VLDL metabolism) (8)(9), VLDL3 (the dense VLDL subclass) (10)(11), and TG-rich chylomicron remnants (8)(12)(13). Despite awareness of the myriad IR-associated proatherogenic lipoprotein abnormalities (1)(2)(3)(4)(5)(14)(15)(16)(17), we are unaware of previous publications in which both IR and all relevant lipoproteins were quantified in the same cohort of individuals. This is likely partly attributable to the unavailability of analytical methods to measure multiple lipoprotein CHD risk factors in a clinically useful manner. However, the validated vertical auto profile-II (VAP-II) methodology (18) provides a means to comprehensively identify the IR-associated dyslipidemic profile, and we have used VAP-II to compare lipoprotein characteristics of nondiabetic individuals stratified into IR and insulin-sensitive (IS) groups. The Stanford University Human Subjects Committee approved this study, and healthy volunteers from the San Francisco Bay Area gave informed consent. Participants underwent medical interview, anthropometric measurements, and a physical examination. Exclusion criteria included fasting plasma glucose >7.0 mmol/L (126 mg/dL), total bilirubin >34 μmol/L (2.0 …

Pravastatin: a review of its use in elderly patients.

Pravastatin (Pravachol) is a competitive, reversible HMG-CoA reductase inhibitor that lowers serum cholesterol levels by inhibiting de novo cholesterol synthesis and has antiatherogenic effects that appear to be partially independent of its lipid-lowering effects. Pravastatin 10-40 mg/day produced significant reductions (vs baseline or placebo) in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in elderly patients (aged >or=60 or >or= 65 years) with hypercholesterolaemia or normal cholesterol levels. Serum triglyceride and high-density lipoprotein cholesterol levels also improved in some studies, but not in others. Coadministration of cholestyramine, another lipid-lowering agent, further enhanced the lipid-lowering effects of pravastatin in elderly patients. Data from the large, long-term (3-6 years) PROspective Study Of Pravastatin in the Elderly at Risk (PROSPER), Cholesterol And Recurrent Events trial (CARE) and Long term Intervention with Pravastatin in Ischaemic Disease (LIPID) trials demonstrated that pravastatin 40 mg/day reduces coronary events in elderly patients with hypercholesterolaemia or normal cholesterol levels, with or at high risk of developing coronary heart disease (CHD). In these trials, the incidence of death from CHD or the combined endpoint of death from CHD or nonfatal myocardial infarction was significantly lower in pravastatin than in placebo recipients. Pravastatin is well tolerated in the elderly, and adverse effects considered related to therapy are minimal. The most commonly occurring adverse events included gastrointestinal events, renal or genital system events, respiratory disorders, headaches and musculoskeletal pain. Pravastatin effectively lowers serum TC and LDL-C levels and, as demonstrated in major clinical outcome trials, reduces coronary events in elderly patients with hypercholesterolaemia or normal cholesterol levels. Pravastatin is well tolerated and as such should be considered a first-line agents for primary or secondary prevention in older individuals with evident CHD or multiple risk factors for CHD.

Baseline characteristics of participants in the Raloxifene Use for The Heart (RUTH) trial

The Raloxifene Use for The Heart (RUTH) trial is a randomized, placebo-controlled, double-blind trial designed to determine whether raloxifene 60 mg/day compared with placebo lowers the risk of coronary events (coronary death, nonfatal myocardial infarction [MI], or hospitalized acute coronary syndromes other than MI) and reduces the risk of invasive breast cancer in women at risk for a major coronary event. Raloxifene is a selective estrogen receptor modulator that improves cardiovascular risk factors, reduces the risk of vertebral fracture, and is associated with a reduced incidence of invasive breast cancer in postmenopausal women with osteoporosis. Between June 1998 and August 2000, 10,101 women were enrolled at 187 sites in 26 countries. Approximately half of the women had documented coronary heart disease (CHD) (n = 5,031); the remainder had multiple CHD risk factors that increased their risk for a CHD event (n = 5,070). The mean age of participants was 68 years (39% were >70 years old), and did not differ between those with documented CHD and those at increased CHD risk. Most women were Caucasian (84%); 60% had a body mass index ≥27 kg/m 2, 46% had diabetes mellitus, 78% had systemic hypertension, and 14% had low-density lipoprotein cholesterol >160 mg/dl. Compared with women at increased CHD risk, women with documented CHD had higher cardiovascular risk scores, a higher prevalence of abnormal electrocardiograms, greater use of cardiovascular medications, were more likely to have had cardiac rehabilitation, and were more likely to have previously used estrogen or oral contraceptives, but had a slightly lower prevalence of CHD risk factors such as smoking, obesity, diabetes mellitus, and systemic hypertension, and had lower serum levels of total and low-density lipoprotein cholesterol. The RUTH cohort is the largest group of postmenopausal women at increased risk of CHD events ever assembled in a clinical trial, and is the first trial designed to determine the effect of a selective estrogen receptor modulator on the risk of CHD events.

Multiple coronary risk factors in healthy older Kuwaiti males.

The objective was to examine the percentage and severity of obesity and some common biochemical coronary heart disease (CHD) risk factors in a sample of healthy Kuwaiti adult males > or =45 y of age. We also sought to determine the percentage of males at increased risk due to the presence of multiple CHD risk factors. The study was a cross-sectional study. The study was conducted in all men who underwent a mandatory job related physical examination or who sought to obtain retirement benefits. A total of 740 healthy Kuwaiti males between the ages of 45 to 80 y. In all, 37% of the men were obese, 26% had elevated glucose values and 52% had elevated or high cholesterol levels. Some had multiple risk factors for CHD, including age > or =45 y, obesity, male gender, hyperglycemia and hypercholesterolemia. Blood glucose values increased consistently from younger (45-54 y) to older age groups (55-64 and > or =65 y). Blood glucose values varied inversely with education level. In societies with relatively uniform income levels, educational level may be a better indicator of chronic disease risk than income per se. These results, showing a high percentage of men with several risk factors and high mean values, suggesting more severe risk, suggest that immediate action should be taken to develop a public health intervention strategy to educate Kuwaiti men to become aware of the causes and correlates of CHD and how to decrease their risk for CHD and heart attack, the leading cause of death in Kuwait.

Effect of a multimodality natural medicine program on carotid atherosclerosis in older subjects: a pilot trial of Maharishi Vedic Medicine

Although the onset and progression of coronary heart disease (CHD) involve multiple risk factors, few intervention studies have attempted to modify these factors simultaneously. This pilot study tested the effect of a multimodality intervention involving dietary, exercise, herbal food supplement, and stress reduction approaches from a traditional system of natural medicine, Maharishi Vedic Medicine (MVM). The primary outcome measure was carotid intima-media thickness (IMT), a noninvasive measure of peripheral atherosclerosis and surrogate measure of coronary atherosclerosis. Comparison groups included modern medicine (conventional dietary, exercise, and multivitamin approaches) and usual care (no added intervention). Of 57 healthy seniors (mean age 74 years) randomized to the 3 treatment groups, 46 completed IMT post-testing. Carotid IMT was determined by B-mode ultrasound before and after 1 year of treatment. IMT decreased in a larger fraction of MVM subjects (16 of 20) than in the modern (5 of 9) and usual care (7 of 14) groups combined (i.e., 12 of 23; odds ratio 3.7, p = 0.05). For subjects with multiple CHD risk factors (“high-risk” subjects, n = 15), IMT decreased more in the MVM (−0.32 ± 0.23 mm, mean ± SD) than in the usual care (+0.022 ± 0.085; p = 0.009) or modern (−0.082 ± 0.095, p = 0.10) groups. Within-group reductions in IMT were significant for all MVM subjects (−0.15 ± 0.21, n = 20, p = 0.004) and for high-risk MVM subjects (n = 6, p = 0.01). These results show that this multimodality traditional approach can attenuate atherosclerosis in older subjects, particularly those with marked CHD risk.

Multiple CHD risk factors in type 2 diabetes: beyond hyperglycaemia

Recent evidence from the United Kingdom Prospective Diabetes Study convincingly demonstrates that good glycaemic control is difficult to achieve and, despite its positive impact on microvascular complications, is not sufficient to reduce the risk of coronary heart disease (CHD). Syndrome X--a cluster of abnormalities associated with resistance to insulin-mediated glucose uptake that have been implicated in accelerating atherogenesis--provides a useful clinical concept to prevent CHD in patients with type 2 diabetes. Components of syndrome X can include hypertension, hyperinsulinaemia, dyslipidaemia, and a procoagulant state, changes that contribute to the development of atherosclerosis. Low-density lipoprotein cholesterol (LDL-C) levels are usually close to normal, but the LDL-C is present in abnormally small and dense particles. Triglyceride levels are elevated and are associated with an increase in postprandial accumulation of atherogenic, remnant lipoprotein particles. High-density lipoprotein cholesterol levels are typically low. This particular dyslipidaemia, along with hyperinsulinaemia, induces expression of plasminogen activator inhibitor-1, contributing to a prothrombotic state. In addition, plaque formation may be accelerated in insulin-resistant subjects by increased expression of adhesion molecules on endothelial cells and increased rate of monocyte adhesion to cultured endothelial cells. Syndrome X and type 2 diabetes are associated with multiple abnormalities that enhance the atherosclerotic process. The opportunities for new therapeutic approaches to reduce cardiovascular risk will undoubtedly evolve along with our understanding of the complex factors responsible for insulin resistance, compensatory hyperinsulinaemia, and CHD.

Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests.

At least 25% of coronary patients have sudden death or nonfatal myocardial infarction without prior symptoms.1 Therefore, the search for coronary patients with subclinical disease who could potentially benefit from intensive primary prevention efforts is critically important. The American Heart Association’s (AHA) Prevention V Conference, “Beyond Secondary Prevention: Identifying the High Risk Patient for Primary Prevention,” addressed ways to identify more patients who are asymptomatic and clinically free of coronary heart disease (CHD) but at sufficiently high risk for a future coronary event to justify more intensive risk reduction efforts.2 In this report, we amplify on key findings and recommendations of the AHA Prevention V conference, highlight new research since the conference, and propose an approach to the use of office-based testing and additional noninvasive procedures in selected patients to better define their coronary event risk. The recommendations are concordant with the recently released approach to risk assessment and management from the third report of the Adult Treatment Panel of the National Cholesterol Education Program (ATP-III).3 Enthusiasm for primary prevention and risk assessment in asymptomatic people has been spurred by recent advances in prevention research. Lipid-lowering trials demonstrated that primary prevention of coronary events is feasible, evidenced by the West of Scotland Coronary Primary Prevention Study (WOSCOPS) trial4 of hypercholesterolemic men and by the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) trial5 in average or typical risk men and women with only moderate lipid abnormalities. Aspirin6 or ACE inhibitors7 can also reduce risk in selected asymptomatic, high-risk people. Emerging coronary risk factors have been described including inflammatory, infectious, and thrombotic markers,8 and there has been a steady flow of reports that focus attention on potential new ways of predicting coronary risk.9 In addition, noninvasive tests for subclinical atherosclerotic disease are available …

Design and methods of the Raloxifene Use for The Heart (RUTH) study

Raloxifene is a selective estrogen receptor modulator that lowers total and low-density lipoprotein (LDL) cholesterol, reduces the risk of vertebral fracture, and is associated with a reduced incidence of invasive breast cancer in postmenopausal women with osteoporosis. The Raloxifene Use for The Heart (RUTH) trial is designed to determine whether raloxifene 60 mg/day compared with placebo: (1) lowers the risk of the coronary events (coronary death, nonfatal myocardial infarction [MI], or hospitalized acute coronary syndromes other than MI); and (2) reduces the risk of invasive breast cancer in women at risk for a major coronary event. RUTH is a double-blind, placebo-controlled, randomized clinical trial of 10,101 postmenopausal women aged ≥55 years from 26 countries. Women are eligible for randomization if they are postmenopausal and have documented coronary heart disease (CHD), peripheral arterial disease, or multiple risk factors for CHD. Use of estrogen within the previous 6 months is an exclusion factor. The study will be terminated after a minimum of 1,670 participants experience a primary coronary end point. Secondary end points include cardiovascular death, myocardial revascularization, noncoronary arterial revascularization, stroke, all-cause hospitalization, all-cause mortality, all breast cancers, clinical fractures, and venous thromboembolic events, in addition to the individual components of the composite primary coronary end point. RUTH will provide important information about the risk-benefit ratio of raloxifene in preventing acute coronary events and invasive breast cancer, as well as information about the natural history of CHD in women at risk of major coronary events.

Obesity and Coronary Heart Disease

Obesity is commonly cited as a risk factor for the development of coronary heart disease (CHD). Epidemiologic studies tend to support this contention, particularly those focusing on patients with central obesity. Such studies however, are imprecise and prone to misclassification bias. Angiographic and post mortem studies have demonstrated little or no correlation of total fat mass and coronary atherosclerosis except in those with abdominal obesity. There is a strong association of obesity, particularly central obesity, and traditional risk factors for CHD such as hypertension, type II diabetes mellitus, and dyslipidemia. There may also be an association between obesity and several nontraditional risk factors such as hyperhomocystinemia, elevated Lp(a) levels and factors that increase thrombogenesis. Obesity may also alter endothelial function. Weight loss, although associated with favorable modification of multiple risk factors for CHD, has not been shown to independently and definitively reduce CHD risk.

A comparison of the efficacy and tolerability of titrate-to-goal regimens of simvastatin and fluvastatin: a randomized, double-blind study in adult patients at moderate to high risk for cardiovascular disease

Background: Use of cholesterol-lowering regimens has been shown to reduce the risk of coronary heart disease (CHD), both in primary and secondary prevention. However, there have been few studies of the relative benefits and risks of the various cholesterol-lowering agents in patients groups with specific risk factors for CHD. Objective: The primary goal of this study was to compare the proportions of adult patients with primary hypercholesterolemia and a moderate to high risk for CHD achieving National Cholesterol Education Program low-density lipoprotein cholesterol (LDL-C) goals with titrate-to-goal regimens of simvastatin and fluvastatin. Methods: This was a multicenter, prospective, randomized, double-blind, parallel-group study enrolling adult patients with type IIa or IIb primary hypercholesterolemia, LDL-C levels <6.0 mmol/L (<232.0 mg/dL), and triglyceride levels <4.5 mmol/L (<398.6 mg/dL), and either CHD or other atherosclerotic disease (the CHD, or high-risk, group), or multiple risk factors for CHD (the MRF, or moderate-risk, group). After a 6-week washout period, patients were randomized to 18 weeks of treatment at an initial dosage of simvastatin 10 mg once daily or fluvastatin 20 mg once daily. At 6- and 12-week titration visits, the dosage in patients who had not acheived the LDL-C goal could be increased to simvastatin 20 mg once daily and then 40 mg once daily, or to fluvastatin 40 mg once daily and then 40 mg twice daily. Lipid profiles were obtained at each titration visit and at the end of treatment. In addition to the comparison between treatments, secondary comparisons were made between the CHD and MRF subgroups within each treatment group. Statistical significance was assessed using analysis of variance. Results: A total of 478 patients were enrolled, 237 in the simvastatin group and 241 in the fluvastatin group. There were no significant between-group differences in patients' characteristics at baseline. At the end of the study, 60.8% (135/222) of patients in the simvastatin group had reached target LDL-C goals, compared with 35.1% (76/216) in the fluvastatin group ( P < 0.001). In the simvastatin CHD and MRF subgroups, 49% and 73%, respectively, reached the LDL-C target, compared with 19% and 50% in the corresponding fluvastatin subgroups ( P < 0.001). The proportion of patients requiring titration was higher in the fluvastatin group than in the simvastatin group (87.1% and 64.1%, respectively; P = 0.001). The incidence of adverse events was similar between groups. Conclusion: In this study, more patients with primary hypercholesterolemia and CHD or multiple risk factors for CHD reached LDL-C goals with simvastatin treatment and required less titration than those who received fluvastatin treatment.