Treatment Of High Blood Cholesterol Research Articles

Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure

Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure

Commentary: Obesity and cardiovascular disease risk among the young and old—is BMI the wrong benchmark?

Wannamethee G, Shaper AG. Body weight and mortality in middle aged British men: impact of smoking. BMJ 1989;299: 1497–502. 23 Hosegood V, Campbell OM. Body mass index, height, weight, arm circumference, and mortality in rural Bangladeshi women: a 19-y longitudinal study. Am J Clin Nutr 2003;77:341–47. 24 Song YM, Sung J. Body mass index and mortality: a twelve-year prospective study in Korea. Epidemiology 2001;12:173–79. 25 Stevens J, Cai J, Pamuk ER, Williamson DF, Thun MJ, Wood JL. The effect of age on the association between body-mass index and mortality. N Engl J Med 1998;338:1–7. 26 Korean Ministry of Health and Welfare. The Korean National Health Nutrition Examination Survey, 1998. Seoul: Korean Ministry of Health and Welfare, 1999. 27 Korean Ministry of Health and Welfare. The Korean National Health Nutrition Examination Survey, 2001. Seoul: Korean Ministry of Health and Welfare, 2002. 28 Park HS, Yun YS, Park JY, Kim YS, Choi JM. Obesity, abdominal obesity, and clustering of cardiovascular risk factors in South Korea. Asia Pac J Clin Nutr 2003;12:411–18. 29 Korean National Statistical Office. 2000 Report of Statistics in Mortality in Korean. Daejon: Korean National Statistical Office, 2001. 30 Chobanian AV, Bakris GL, Black HR et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560–72. 31 Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003;26 (Suppl 1):S5–20. 32 NHLBI. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486–97. 33 Allison DB, Heo M, Flanders DW, Faith MS, Williamson DF. Examination of ‘‘early mortality exclusion’’ as an approach to control for confounding by occult disease in epidemiologic studies of mortality risk factors. Am J Epidemiol 1997;146:672–80. 34 Wannamethee SG, Shaper AG, Morris RW, Whincup PH. Measures of adiposity in the identification of metabolic abnormalities in elderly men. Am J Clin Nutr 2005;81:1313–21. 35 Turcato E, Bosello O, Di Francesco V et al. Waist circumference and abdominal sagittal diameter as surrogates of body fat distribution in the elderly: their relation with cardiovascular risk factors. Int J Obes Relat Metab Disord 2000;24:1005–10.

Therapeutic Goal Attainment in Patients With Hypertension and Dyslipidemia

Recent guidelines emphasize the need to assess and treat overall risk for cardiovascular disease through the concomitant management of multiple risk factors. We sought to ascertain treatment patterns and attainment of therapeutic goals in patients with isolated and concomitant hypertension and dyslipidemia, both with and without diabetes mellitus (DM) and symptomatic cardiovascular disease. Inception cohorts of more than 41,000 newly diagnosed hypertension and dyslipidemia patients from 6 medical centers of the south-central Veterans Affairs health care system were evaluated. Treatment patterns and goal attainment for low-density lipoprotein cholesterol (LDL-C; Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults guidelines: <160, <130, or <or=100 mg/dL depending on risk factors) and blood pressure (BP; Joint National Committee 6: <140/90 or <130/85 mm Hg depending on risk factors) were measured at 1 year. Separate analyses were conducted in patients with and without DM and symptomatic cardiovascular disease. Treatment rates in patients with and without DM and symptomatic disease ranged from 46.6% to 71.3% in patients with hypertension only, from 31.5% to 64.1% in patients with dyslipidemia only, and from 64.3% to 91.3% in patients with both conditions. Among asymptomatic patients, 40.6% of nondiabetics and 20.6% of patients with DM with isolated hypertension reached BP targets. Attainment of LDL-C goals was slightly higher and reached 52.8% among patients with DM with concomitant hypertension. Among symptomatic patients, attainment of all goals was <40% for all groups. The proportion of asymptomatic patients with concomitant disease reaching goal for both BP and LDL-C was 24.4% among nondiabetics and 15.4% among patients with DM; these proportions decreased to 13.6% and 13.4% respectively, among patients with symptomatic cardiovascular disease. The majority of patients were receiving pharmacological treatment of hypertension and dyslipidemia, yet attainment of therapeutic goals was generally <50%. Further work is needed to determine factors related to improvement in management and outcomes of patients with multiple cardiovascular risk factors.

Contemporary strategies for managing cardiometabolic risk factors.

To review the metabolic syndrome as defined by the 2001 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) and its modifiable risk factors and to review currently available treatment modalities. Metabolic syndrome, although still controversial, is a growing concern. Most definitions include elevated blood pressure, smoking, inflammation, insulin resistance, abdominal adiposity, elevated blood glucose, and atherogenic dyslipidemia as modifiable risk factors. Some researchers believe that additional signs of inflammation such as plasminogen activator inhibitor-1 and C-reactive protein should be added to this list. Current treatment options include lifestyle changes (diet and exercise), pharmacotherapy, and bariatric surgery. The endocannabinoid system appears to play a key role in metabolism and weight gain. The investigational agent rimonabant is a cannabinoid receptor type 1 blocker that has been employed in numerous trials involving more than 6,500 patients. It has led to significant weight loss, reduced central fat, and improved glycemic and lipid profiles.

‘Hypertension’ and ‘microalbuminuria’: The bell tolls for thee

Since the terms 'hypertension' and 'microalbuminuria' were first defined, data from numerous studies have documented the continuous, rather than dichotomous, relation between blood pressure, albumin excretion, and cardiovascular disease. Lower blood pressures, down to at least 115/75 mmHg, and lower albumin excretions, below an estimated 2 mg/day, are associated with less cardiovascular risk. We hypothesize that the abundances of modern civilization superimposed on the Paleolithic genotype of humans, which has not substantially changed in the last 10 000 years, have considerably shifted the 'normal' values for blood pressure and various biochemical indices such as albuminuria still found in today's stone-aged cultures to the 'neo-normal' values observed today in the rest of the modern world. Defining a large portion of the population as 'normal' based upon these dichotomous 'neo-normal' standards is not supported by the data, and therefore seems unjustifiable. We propose that the medical community consider abandoning the terms 'hypertension' and 'microalbuminuria' in favor of 'blood pressure-associated' and 'albuminuria-associated' disease.

Lack of Effect of Guideline Changes on LDL Cholesterol Reporting and Control for Diabetes Visits in the U.S., 1995–2004

We studied the effects of guideline changes on LDL cholesterol reporting and control for diabetes visits compared with coronary heart disease (CHD) visits in the U.S. between 1995 and 2004. In January 1998, the American Diabetes Association (ADA) advocated an LDL cholesterol goal of <100 mg/dl for patients with diabetes (1). Subsequently, in May 2001, the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults published its third report (Adult Treatment Panel III [ATP III]) that designated diabetes as a CHD risk equivalent, with the same LDL cholesterol goal of <100 mg/dl (2). The publication of the ADA and ATP III guidelines provides an opportunity to assess the effect of guideline changes on LDL cholesterol reporting and control for diabetes visits. The publication of guidelines does not ensure timely communication to the practicing physician let alone the adoption into patient care. As the treatment strategy for CHD remained unchanged (2), we used CHD visits as the control group for the time trends of LDL cholesterol reporting and control. We used the National Disease and Therapeutic Index (NDTI) (3), an ongoing survey of U.S. office-based physicians conducted by IMS Health providing nationally representative diagnostic and treatment data, to analyze the national trends …

Metabolic Syndrome and Cardiovascular Disease

Metabolic syndrome is a constellation of clinical findings that identify individuals at higher than normal risk of developing diabetes mellitus or cardiovascular disease. There are two principal definitions, one emerging from the American National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, and the other from the World Health Organization. Both definitions share the common elements of abdominal obesity, hypertriglyceridaemia, low HDL-cholesterol, hypertension and abnormal glucose regulation. The syndrome is relatively common across continents, and also among those without marked obesity. It is even more common among patients with major mental health disorders such as schizophrenia. Metabolic syndrome can be used to assess risk for cardiovascular disorder and death, and is an alternative to Framingham Risk Calculations. C-reactive protein may play an additional role in risk prediction. Ongoing monitoring for all components of the metabolic syndrome is necessary. Individuals at high risk require multimodal interventions, including lifestyle interventions and targeted medications as appropriate.

Insulin Resistance, the Metabolic Syndrome, and Incident Cardiovascular Events in the Framingham Offspring Study

The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMA-IR) and by Gutt et al.'s insulin sensitivity index (ISI(0,120)). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age- and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5-2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2-2.9], P = 0.003; and for ISI(0,120) [both highest versus lowest quartile]: 0.5 [0.3-0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI(0,120) levels were independently related to incident CVD (0.5 [0.3-0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8-2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P < or = 0.007 in both). In conclusion, metabolic syndrome and ISI(0,120) but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance.

The Metabolic Syndrome: A Cause of Sexual Dysfunction in Women

No AccessJournal of UrologyUrological Survey: Male and Female Sexual Function and Dysfunction; Andrology1 Oct 2005The Metabolic Syndrome: A Cause of Sexual Dysfunction in Women Allen D. SeftelM.D. Allen D. SeftelAllen D. Seftel More articles by this author View All Author Informationhttps://doi.org/10.1097/S0022-5347(01)68635-XAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "The Metabolic Syndrome: A Cause of Sexual Dysfunction in Women." The Journal of Urology, 174(4 Part 1), pp. 1364–1365 References 1 : Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Washington, D. C.: United States Department of Health and Human Services2001. NIH Publication No. 01-3670. Google Scholar © 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 174Issue 4 Part 1October 2005Page: 1364-1365 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.MetricsAuthor Information Allen D. Seftel More articles by this author Expand All Advertisement PDF DownloadLoading ...

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.

Association Between Peroxisome Proliferator–Activated Receptor γ Haplotypes and the Metabolic Syndrome in French Men and Women

We assessed the association of four polymorphisms (promoter P3 -681C>G, P2 -689C>T, Pro12Ala, and 1431C>T) in peroxisome proliferator-activated receptor gamma (PPARgamma) with the metabolic syndrome risk in a large, French population study (n = 1,155). In this sample, 279 men and women presented with metabolic syndrome according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. When taken individually, none of the polymorphisms was significantly associated with the metabolic syndrome. Haplotype analyses, in contrast, revealed a significant enrichment of the GTGC haplotype frequency (corresponding to the P3 -681C>G, P2 -689C>T, Pro12Ala (C/G), and 1431C>T polymorphisms in this order) among those with metabolic syndrome compared with control subjects. Compared with the most common CCCC haplotype, the adjusted odds ratio (OR) (95% CI) of the metabolic syndrome for bearers of the GTGC haplotype was 2.37 (1.42-3.95; P = 0.002), 1.92 (1.00-3.72; P = 0.05), and 2.47 (1.09-5.62; P = 0.045) in the whole sample of men and women, respectively. Similar results were obtained when using another haplotype (GCCC, GTGT, CCCT, or GCCT) as a reference. Furthermore, when the GTGC haplotype frequency was tested alone (i.e., versus the frequency of the five other haplotypes together), the OR (95% CI) of the metabolic syndrome was 2.30 (1.05-5.00; P = 0.022). These data show that only the frequency of the GTGC haplotype was different between subjects with and without metabolic syndrome. Further analyses stratified on the 1431C>T single nucleotide polymorphism (SNP) indicated that the rare alleles of the P2 -689C>T and Pro12Ala SNPs were associated with an increased risk of the metabolic syndrome when combined to the 1431CC genotype. In conclusion, a specific haplotype of PPARgamma polymorphisms is associated with an increased risk of the metabolic syndrome in a French general population.

Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians

This study sought to evaluate the presence of the metabolic syndrome in a group of 171 patients with bipolar disorder who were consecutively recruited in the Bipolar Disorder Center for Pennsylvanians. Data were collected from participants entering the Bipolar Disorder Center for Pennsylvanians protocol between 2003 and 2004. The study focused on the presence of the metabolic syndrome, as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation And Treatment of High Blood Cholesterol in Adults (NCEP ATP III). Thirty percent of the sample met the NCEP ATP III criterion for the metabolic syndrome, 49% met the criterion for abdominal obesity, 41% met the criterion for hypertriglyceridemia, 48% met the criterion for hypertriglyceridemia or were on a cholesterol-lowering medication, 23% met the criterion for low high-density lipoprotein cholesterol, 39% met the criterion for hypertension and 8% met the criterion for high fasting glucose or antidiabetic medication use. Patients with the metabolic syndrome and patients endorsing the obesity criterion were more likely (p = 0.05 and p = 0.004, respectively) to report a lifetime history of suicide attempt/s. The prevalence of the metabolic syndrome in patients with bipolar disorder is alarmingly high, as it is for the general population. The prevalence of obesity is even higher than the already very high prevalence that has been estimated for the US general population. Our findings are a reason for concern, considering the difficulty in implementing prevention and treatment programs in the bipolar population. We strongly support the development and testing of interventions specifically designed for preventing and treating the metabolic syndrome and its components in patients with bipolar disorder.

Hypertension: Definitions and Guidelines

Hypertension: Definitions and Guidelines

Central obesity as a major determinant of increased high-sensitivity C-reactive protein in metabolic syndrome

Traditional cardiovascular risk factors such as central obesity, high blood pressure and insulin resistance, all constituents of metabolic syndrome, have been associated with increased levels of C-reactive protein (CRP). Therefore, this marker of low-grade inflammation may play a major role in the pathogenesis of cardiovascular diseases. In this study, data from a representative sample of urban adults was used to evaluate the association between CRP and metabolic syndrome, accounting for the type and number of its constituents. Using random digit dialing, 1022 participants, aged 18-92 y, were selected. All participants completed a structured questionnaire comprising of information on social, demographic, behavioral and clinical aspects. Anthropometrics and blood pressure were recorded and a fasting blood sample collected. Metabolic syndrome was defined, according to the Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, as the presence of three or more of the following characteristics: waist circumference greater than 102 cm in men and 88 cm in women; triglyceride levels > or = 150 mg/dl; high-density lipoprotein cholesterol levels < 40 mg/dl in men and < 50 mg/dl in women; blood pressure > or = 130/85 mm Hg; and serum glucose > or = 110 mg/dl. High-sensitivity CRP was assessed by immunonephelometric assay. After excluding 65 participants with CRP > or = 10 mg/l, 957 subjects (599 women and 358 men) remained for analysis. Geometric means were compared after adjustment for age, sex, alcohol consumption and smoking. Higher mean levels of CRP (2.34 vs 1.36, P < 0.001) were observed when metabolic syndrome was present. Also, mean CRP levels were significantly higher in the presence of central obesity (2.45 vs 1.24, P < 0.001), high blood pressure (1.76 vs 1.12, P < 0.001), hypertriglyceridemia (2.17 vs 1.32, P < 0.001) and high fasting glucose (1.96 vs 1.46, P = 0.032). We found a significant increasing trend (P < 0.001) in mean levels of CRP as the number of features of metabolic syndrome increased. The major contributing features for high CRP levels were central obesity and high blood pressure. Present data show that increasing severity of metabolic syndrome is associated with increasing CRP. Additionally, we found that central obesity and high blood pressure are the most important determinants of the low-grade chronic inflammation present in metabolic syndrome.

Influence of the metabolic syndrome on aortic stiffness in never treated hypertensive patients

Metabolic syndrome (MS) carries an increased risk for cardiovascular events and there is a growing awareness that large artery stiffening is a powerful predictor of cardiovascular morbidity and mortality. Little is known about the relationship of MS with aortic stiffness. The aim of our study was to analyze, in patients with essential hypertension, the influence of MS, defined according to the criteria proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III), on carotid-femoral pulse wave velocity (PWV), a measure of aortic stiffness. Ninety-three untreated essential hypertensives, aged between 23 and 61 years, without diabetes mellitus, were studied. All subjects underwent routine blood chemistry, oral glucose tolerance test with glucose and insulin determinations, albumin excretion rate (AER) measurement, 24-h ambulatory blood pressure monitoring, and measurement of carotid-femoral PWV, by means of a computerized method. Patients with MS (n = 28) showed higher age-adjusted carotid-femoral PWV (10.1 +/- 1.4 vs 9.3 +/- 1.4 m/s; p = 0.01) when compared to subjects without MS. This difference held after controlling for gender and for 24-h mean blood pressure (MBP) (p = 0.02) and lost its statistical significance after further adjustment for AER. In a multiple regression model, excluding the individual components of MS, in which metabolic syndrome was added along with age, gender, smoking habit, LDL cholesterol, HOMA index, 24-h MBP and 24-h heart rate, MS remained independently associated with carotid-femoral PWV (beta = 0.29; p = 0.002). The statistical significance of this association disappeared after the inclusion into this model of AER. Metabolic syndrome is associated with an increased aortic stiffness. Main explanatory factors of this association are age, systolic blood pressure and albumin excretion rate.

L'hyperhomocystéinémie est-elle un facteur de risque supplémentaire du syndrome métabolique ?

Metabolic syndrome is a cardiovascular risk factors cluster and hyperhomocysteinemia an obvious independant risk factor. To ascertain if hyperhomocysteinemia is associated with the metabolic syndrome. "Epimil" is a prospective epidemiologic survey, which began by a cross-sectionnal study of cardiovascular risk factors in a French population, which then will be followed for ten years for supervision and intervention. Initial data collection, blood pressure measurement, ECG and blood samples (biology and DNA) have been performed. For the metabolic syndrome, we used the criterias of the third report of the national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (NCEP ATP III). Out of 2045 men aged from 20 to 58 years (37.7+/-8.7 years), 185 (9%) have metabolic syndrome (at least three criterias), 587 (29%) a blood homocysteine>or=12 micromol/L and 202 (10%)>or=15 micromol/L. Homocysteinemia is 10.97+/-5.01 micromol/L for the whole population and doesn't differ with (11.4+/-6 micromol/L) or without (10.9+/-5 micromol/L) the metabolic syndrome, as does its values distribution. It's not correlate with the body mass index, waist and hip measurements, nor with glycemia, HbA1c, insulin resistance and cardiovascular risk markers (CRPus, microalbuminuria). It weakly correlates with systolic and diastolic blood pressure, creatinine clearance, tobacco use, cholesterolemia, triglycerides and free fatty acids but not with HDL and LDL fractions, nor lipoprotein (a). Among this population, it slightly contributes to the ten years vascular risk evaluated according to Framingham equations or Score system. Homocysteinemia and the prevalence of hyperhomocysteinemia don't differ with or without the metabolic syndrome and doesn't correlate its main criterias.

CHAPTER 1: THE MANAGEMENT OF ERECTILE DYSFUNCTION: AN AUA UPDATE

approach to develop a guideline for the ED treatment modalities that had become available in the United States after publication of the 1996 Report. Guideline statements from the 1996 Report on previously available therapeutic modalities were either revised or brought forward unchanged depending on the existing evidence. All guideline statements were graded according to the degree of flexibility in clinical application: standard, recommendation, or option, with standard being the least flexible and option being the most flexible (Table 1). Grading is based on two characteristics: knowledge of the health outcomes of the alternative intervention and preference for the intervention. The Panel believed that the patient, with physician guidance, must make his own decision in selecting treatment. Outcome estimates derived from review and meta-analysis of evidence provide physicians and patients with scientifically based information to assist them in making appropriate treatment decisions. Thus, a second Panel objective was to determine whether or not there was sufficient evidence for outcomes (both benefits and risks) to be estimated.

Balancing Unsaturated Fatty Acids: What’s the Evidence for Cholesterol Lowering?

Dietary recommendations for the reduction of low-density lipoprotein cholesterol (LDL-C) emphasize lowering intake of saturated fatty acids (SFA) and trans-fatty acids ( 1 Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001; 285: 2486-2497 Google Scholar ). It has also been recommended that carbohydrate and/or unsaturated fat can replace these fats to maintain the caloric needs of individuals. Unsaturated fats consist of polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). Research focused on potentially greater health benefits of monounsaturated fats vs polyunsaturated fats has not been consistent. In addition to their effects on lipid profiles, the consequences related to oxidative stress have also been studied. In this issue of the Journal, Binkoski and colleagues ( 2 Binkoski A.E. Kris-Etherton P.M. Wilson T.A. Mountain M.L. Nicolosi R.J. Balance of unsaturated fatty acids is important to a cholesterol-lowering diet Comparison of mid-oleic sunflower oil and olive oil on cardiovascular disease risk factors. J Am Diet Assoc. 2005; 105: 1080-1086 Google Scholar ) report on the comparison of mid-oleic sunflower oil and olive oil on cardiovascular disease risk factors. This was a double-blinded, randomized, three-period crossover, controlled feeding study in 31 moderately hypercholesterolemic men and women, 25 to 64 years of age. The authors examined lipids, lipoproteins, and measures of oxidative stress after 4 weeks on each diet. The mid-oleic acid sunflower oil diet contributing 7.7% SFA, 14.2% MUFA, and 7.7% PUFA decreased both total and LDL-C compared to the average American diet (11.2% SFA, 14.9% MUFA, and 7.8% PUFA) and the olive oil diet (8.3% SFA, 17.2% MUFA, and 4.3% PUFA). W. Karmally is director of nutrition, The Irving Center for Clinical Research, Columbia University Medical Center, New York, NY.

Pharmacologic Options for Aggressive Low-Density Lipoprotein Cholesterol Lowering: Benefits Versus Risks

Lessons from recent end point trials of lipid-lowering drugs indicate that patients at very high risk for coronary artery disease (CAD) benefit from treatment that lowers low-density lipoprotein (LDL) cholesterol plasma levels to < or = 1.81 mmol/L (< or = 70 mg/dL), that patients with > or = 2 risk factors benefit from treatment that lowers plasma LDL cholesterol to <2.59 mmol/L (<100 mg/dL), and that a significant reduction in CAD event rates is most often associated with a minimum plasma LDL cholesterol reduction of 30%. Recently, the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) recommendations were amended to incorporate these lessons. To reach these more aggressive goals and plasma LDL cholesterol reductions, more aggressive therapies will be required. The best way to implement more aggressive therapy is to start with one of the more potent statins, especially atorvastatin or rosuvastatin, or higher doses of other statins. This approach alone is likely to achieve treatment goals in 50% to 80% of patients. For patients needing additional plasma LDL cholesterol lowering, combination therapies will be required. Adding colesevelam, ezetimibe, or niacin to a stable statin regimen will generally provide an additional 10% to 15% lowering of plasma LDL cholesterol. These more potent statins, even when used in higher doses, appear to be safe. The incidence of myopathy and rhabdomyolysis, as documented in long-term clinical trials, is <0.1% and <0.01%, respectively, except for simvastatin, which has a higher incidence of these problems. Less information is available about the safety of lowering levels of plasma LDL cholesterol to < or = 1.81 mmol/L (< or = 70 mg/dL), but an analysis of a recent 2-year-long clinical trial, in which patients had on-treatment plasma LDL cholesterol levels as low as 0.67 mmol/L (26 mg/dL), reported no signals of untoward effects in patients with progressively lower levels.

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD)

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD). Cardiovascular calcification (CVC) is commonly encountered both in the general population as well as in patients with end-stage renal disease (ESRD). The etiology of CVC in patients with ESRD is multifactorial. Despite that, current debate remains narrowly focused on the role of calcium loading from calcium-based phosphate binders (CBPB) in the pathogenesis and progression of CVC. Yet, the alleged link between these binders and CVC has not been substantiated in well-designed controlled trials. In contrast, the purported role of sevelamer, a non-calcium-based phosphate binder, in slowing the progression of CVC in dialysis patients has attracted widespread attention. The beneficial effect of sevelamer on progression of calcification was thought to be due to lower calcium loading during its use. However, an alternative and possibly more likely mechanism involves sevelamer-induced lowering of LDL cholesterol. In this context, previous studies in individuals with normal renal function have documented amelioration of coronary artery calcification (CAC) with reduction of LDL-cholesterol by treatment with HMG-CoA reductase inhibitors (statins). Given that CAC is a well-accepted marker of atherosclerosis, and that high plasma cholesterol concentration is one of the main risk factors for atherosclerosis, then it is not unreasonable to suspect that CAC may be halted or even reversed by lowering of LDL cholesterol level with statin therapy. Unfortunately, the effect of lowering the LDL-cholesterol level on CAC has not been studied in patients with ESRD. Therefore, conclusions about this important topic should await the results of well-designed clinical studies that control for all factors potentially implicated in the CVC burden of patients with ESRD. In this review, I will discuss the role of various potential mechanisms involved in the pathogenesis of CVC in patients with ESRD, and emphasize the role of dyslipidemia and its treatment in this important clinical entity.