Grundy SM Research Articles

Statin Intolerance and Noncompliance: An Empiric Approach

Statin Intolerance and Noncompliance: An Empiric Approach

Performance of the Pooled Cohort Equations in Hispanic Individuals Across the United States: Insights From the Multi‐Ethnic Study of Atherosclerosis and the Dallas Heart Study

Performance of the Pooled Cohort Equations in Hispanic Individuals Across the United States: Insights From the Multi‐Ethnic Study of Atherosclerosis and the Dallas Heart Study

ETHANOLIC EXTRACT OF TUBTIM-CHUMPHAE RICE BRAN DECREASES INSULIN RESISTANCE AND INTRAHEPATIC FAT ACCUMULATION IN HIGH-FAT-HIGH-FRUCTOSE DIET FED RATS

Objective: Tubtim-chumphae rice is hybrid Thai rice with a red pericarp. This study was aimed to investigate the effect of Tubtim-chumphae rice bran on insulin resistance and intrahepatic fat accumulation in high-fat-high-fructose diet (HFFD) fed rats.Methods: Ethanolic extract of rice bran (ERB) was prepared using a 50% ethanol-water. Male Sprague-Dawley rats were fed HFFD (40% lard, 20% fructose) for 10 weeks, followed by concomitant administrations of distilled water or ERB at 250 or 500 mg/kg/day or pioglitazone at 10 mg/kg/day for a further 4 weeks in treated groups. Normal control rats were fed normal chow and distilled water. At the end of all treatments, fasting blood glucose (FBG), an oral glucose tolerance test (OGTT), serum insulin levels, lipid profiles, and liver fat contents were measured. Liver histological and peroxisome proliferator-activated receptor-α (PPAR-α) gene expression examinations were performed.Results: At week 14, control HFFD rats had significantly (p<0.05) higher FBG, low-density lipoprotein cholesterol, triglycerides, and insulin secretions together with impaired OGTT as compared to normal control rats. These parameters indicated an insulin resistant and dyslipidemic condition in HFFD rats. ERB 250 and 500 mg/kg or pioglitazone 10 mg/kg significantly ameliorated all of these changes. HFFD also caused a significant increase in fat accumulation and a decrease in PPAR-α gene expression in the livers which were significantly decreased by ERB.Conclusions: ERB decreases insulin resistance and intrahepatic fat accumulation possibly through increasing PPAR-α gene expression in HFFD rats. ERB might possibly be a neutraceutical for the metabolic syndrome patients.1. Gauthier MS, Favier R, Lavoie JM. Time course of the development of non-alcoholic hepatic steatosis in response to high-fat diet-induced obesity in rats. Br J Nutr 2006;95:273-81.2. Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: Underlying causes and modification by exercise training. Compr Physiol 2013;3:1-58.3. Grundy SM. Metabolic syndrome update. Trends Cardiovasc Med 2016;26:364-73.4. Fouret G, Gaillet S, Lecomte J, Bonafos B, Djohan F, Barea B, et al. 20-week follow-up of hepatic steatosis installation and liver mitochondrial structure and activity and their interrelation in rats fed a high-fat-high-fructose diet. Br J Nutr 2018;119:368-80.5. Dekker MJ, Su Q, Baker C, Rutledge AC, Adeli K. Fructose: A highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome. Am J Physiol Endocrinol Metab 2010;299:E685-94.6. Vichit W, Saewan N. Antioxidant activities and cytotoxicity of thai pigmented rice. Int J Pharm Pharm Sci 2015;7:329-34.7. Settharaksa S, Madaka F, Charkree K, Charoenchai L. The study of anti-inflammatory and antioxidant activity in cold press rice bran oil from rice in Thailand. Int J Pharm Pharm Sci 2014;6:428-31.8. Sukrasno S, Tuty S, Fidrianny I. Antioxidant evaluation and phytochemical content of various rice bran extracts of three varieties rice from Semarang, central Java, Indonesia. Asian J Pharm Clin Res 2017;10:377-82.9. Sabir A, Rafi M, Darusman LK. Discrimination of red and white rice bran from indonesia using HPLC fingerprint analysis combined with chemometrics. Food Chem 2017;221:1717-22.10. Niu Y, Gao B, Slavin M, Zhang X, Yang F, Bao J, et al. Phytochemical compositions, and antioxidant and anti-inflammatory properties of twenty-two red rice samples grown in Zhejiang. LWT Food Sci Technol 2013;54:521-7.11. Boonloh K, Kukongviriyapan V, Kongyingyoes B, Kukongviriyapan U, Thawornchinsombut S, Pannangpetch P, et al. Rice bran protein hydrolysates improve insulin resistance and decrease pro-inflammatory cytokine gene expression in rats fed a high carbohydrate-high fat diet. Nutrients 2015;7:6313-29.12. Peñarrieta JM, Alvarado JA, Akesson B, Bergenståhl B. Total antioxidant capacity and content of flavonoids and other phenolic compounds in canihua (Chenopodium pallidicaule): An andean pseudocereal. Mol Nutr Food Res 2008;52:708-17.13. Mungkhunthod S, Senggunprai L, Tangsucharit P, Sripui J, Kukongviriyapan U, Pannangpetch P. Antidesma thwaitesianum pomace extract improves insulin sensitivity via upregulation of PPAR-γ in high fat diet/streptozotocin-induced Type 2 diabetic rats. Asia Pac J Sci Technol 2016;21:63-76.14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC, et al. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.15. Naowaboot J, Wannasiri S. Anti-lipogenic effect of Senna alata leaf extract in high-fat diet-induced obese mice. Asian Pac J Trop Biomed 2016;6:232-8.16. Couturier K, Qin B, Batandier C, Awada M, Hininger-Favier I, Canini F, et al. Cinnamon increases liver glycogen in an animal model of insulin

ETHANOLIC EXTRACT OF TUBTIM-CHUMPHAE RICE BRAN DECREASES INSULIN RESISTANCE AND INTRAHEPATIC FAT ACCUMULATION IN HIGH-FAT-HIGH-FRUCTOSE DIET FED RATS

Objective: Tubtim-chumphae rice is hybrid Thai rice with a red pericarp. This study was aimed to investigate the effect of Tubtim-chumphae rice bran on insulin resistance and intrahepatic fat accumulation in high-fat-high-fructose diet (HFFD) fed rats.Methods: Ethanolic extract of rice bran (ERB) was prepared using a 50% ethanol-water. Male Sprague-Dawley rats were fed HFFD (40% lard, 20% fructose) for 10 weeks, followed by concomitant administrations of distilled water or ERB at 250 or 500 mg/kg/day or pioglitazone at 10 mg/kg/day for a further 4 weeks in treated groups. Normal control rats were fed normal chow and distilled water. At the end of all treatments, fasting blood glucose (FBG), an oral glucose tolerance test (OGTT), serum insulin levels, lipid profiles, and liver fat contents were measured. Liver histological and peroxisome proliferator-activated receptor-α (PPAR-α) gene expression examinations were performed.Results: At week 14, control HFFD rats had significantly (p<0.05) higher FBG, low-density lipoprotein cholesterol, triglycerides, and insulin secretions together with impaired OGTT as compared to normal control rats. These parameters indicated an insulin resistant and dyslipidemic condition in HFFD rats. ERB 250 and 500 mg/kg or pioglitazone 10 mg/kg significantly ameliorated all of these changes. HFFD also caused a significant increase in fat accumulation and a decrease in PPAR-α gene expression in the livers which were significantly decreased by ERB.Conclusions: ERB decreases insulin resistance and intrahepatic fat accumulation possibly through increasing PPAR-α gene expression in HFFD rats. ERB might possibly be a neutraceutical for the metabolic syndrome patients.1. Gauthier MS, Favier R, Lavoie JM. Time course of the development of non-alcoholic hepatic steatosis in response to high-fat diet-induced obesity in rats. Br J Nutr 2006;95:273-81.2. Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: Underlying causes and modification by exercise training. Compr Physiol 2013;3:1-58.3. Grundy SM. Metabolic syndrome update. Trends Cardiovasc Med 2016;26:364-73.4. Fouret G, Gaillet S, Lecomte J, Bonafos B, Djohan F, Barea B, et al. 20-week follow-up of hepatic steatosis installation and liver mitochondrial structure and activity and their interrelation in rats fed a high-fat-high-fructose diet. Br J Nutr 2018;119:368-80.5. Dekker MJ, Su Q, Baker C, Rutledge AC, Adeli K. Fructose: A highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome. Am J Physiol Endocrinol Metab 2010;299:E685-94.6. Vichit W, Saewan N. Antioxidant activities and cytotoxicity of thai pigmented rice. Int J Pharm Pharm Sci 2015;7:329-34.7. Settharaksa S, Madaka F, Charkree K, Charoenchai L. The study of anti-inflammatory and antioxidant activity in cold press rice bran oil from rice in Thailand. Int J Pharm Pharm Sci 2014;6:428-31.8. Sukrasno S, Tuty S, Fidrianny I. Antioxidant evaluation and phytochemical content of various rice bran extracts of three varieties rice from Semarang, central Java, Indonesia. Asian J Pharm Clin Res 2017;10:377-82.9. Sabir A, Rafi M, Darusman LK. Discrimination of red and white rice bran from indonesia using HPLC fingerprint analysis combined with chemometrics. Food Chem 2017;221:1717-22.10. Niu Y, Gao B, Slavin M, Zhang X, Yang F, Bao J, et al. Phytochemical compositions, and antioxidant and anti-inflammatory properties of twenty-two red rice samples grown in Zhejiang. LWT Food Sci Technol 2013;54:521-7.11. Boonloh K, Kukongviriyapan V, Kongyingyoes B, Kukongviriyapan U, Thawornchinsombut S, Pannangpetch P, et al. Rice bran protein hydrolysates improve insulin resistance and decrease pro-inflammatory cytokine gene expression in rats fed a high carbohydrate-high fat diet. Nutrients 2015;7:6313-29.12. Peñarrieta JM, Alvarado JA, Akesson B, Bergenståhl B. Total antioxidant capacity and content of flavonoids and other phenolic compounds in canihua (Chenopodium pallidicaule): An andean pseudocereal. Mol Nutr Food Res 2008;52:708-17.13. Mungkhunthod S, Senggunprai L, Tangsucharit P, Sripui J, Kukongviriyapan U, Pannangpetch P. Antidesma thwaitesianum pomace extract improves insulin sensitivity via upregulation of PPAR-γ in high fat diet/streptozotocin-induced Type 2 diabetic rats. Asia Pac J Sci Technol 2016;21:63-76.14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC, et al. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.15. Naowaboot J, Wannasiri S. Anti-lipogenic effect of Senna alata leaf extract in high-fat diet-induced obese mice. Asian Pac J Trop Biomed 2016;6:232-8.16. Couturier K, Qin B, Batandier C, Awada M, Hininger-Favier I, Canini F, et al. Cinnamon increases liver glycogen in an animal model of insulin

Does Host Cholesterol Metabolism Impact the Gut Microbiota and why does it Matter?

Future MicrobiologyVol. 8, No. 5 EditorialDoes host cholesterol metabolism impact the gut microbiota and why does it matter?Inés Martínez, Andrew W Brown & Jens WalterInés MartínezDepartment of Food Science & Technology, University of Nebraska, Lincoln, NE 68583-0919, USASearch for more papers by this author, Andrew W BrownNutrition Obesity Research Center & Office of Energetics, University of Alabama at Birmingham, Birmingham, AL 35294, USASearch for more papers by this author & Jens Walter* Author for correspondenceDepartment of Food Science & Technology, University of Nebraska, Lincoln, NE 68583-0919, USA. .Search for more papers by this authorEmail the corresponding author at jwalter2@unl.eduPublished Online:3 May 2013https://doi.org/10.2217/fmb.13.24AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: cholesterol metabolismdysbiosisgut microbiotametabolic syndromeReferences1 Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature489,242–249 (2012).Crossref, Medline, CAS, Google Scholar2 Yokota A, Fukiya S, Islam KBM et al. Is bile acid a determinant of the gut microbiota on a high-fat diet? Gut Microbes3(5),455–459 (2012).Crossref, Medline, Google Scholar3 Martinez I, Perdicaro DJ, Brown AW et al. Diet-induced alterations of host cholesterol metabolism are likely to affect the gut microbiota composition in hamsters. Appl. Environ. Microbiol.79(2),516–524 (2013).Crossref, Medline, CAS, Google Scholar4 Brown AW, Hang J, Dussault PH, Carr TP. Phytosterol ester constituents affect micellar cholesterol solubility in model bile. Lipids45(9),855–862 (2010).Crossref, Medline, CAS, Google Scholar5 Do TQ, Moshkani S, Castillo P et al. Lipids including cholesteryl linoleate and cholesteryl arachidonate contribute to the inherent antibacterial activity of human nasal fluid. J. Immunol.181(6),4177–4187 (2008).Crossref, Medline, CAS, Google Scholar6 Marquart ME, Monds KS, McCormick CC et al. Cholesterol as treatment for pneumococcal keratitis: cholesterol-specific inhibition of pneumolysin in the cornea. Invest. Ophthalmol. Vis. Sci.48(6),2661–2666 (2007).Crossref, Medline, Google Scholar7 Salzman NH, Hung K, Haribhai D et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat. Immunol.11(1),76–83 (2010).Crossref, Medline, CAS, Google Scholar8 Claus SP, Ellero SL, Berger B et al. Colonization-induced host–gut microbial metabolic interaction. mBio2(2),e00271–00210 (2011).Crossref, Medline, Google Scholar9 Martinez I, Wallace G, Zhang C et al. Diet-induced metabolic improvements in a hamster model of hypercholesterolemia are strongly linked to alterations of the gut microbiota. Appl. Environ. Microbiol.75(12),4175–4184 (2009).Crossref, Medline, CAS, Google Scholar10 Spencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology140(3),976–986 (2011).Crossref, Medline, CAS, Google Scholar11 Zhang C, Zhang M, Wang S et al. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J.4(2),232–241 (2010).Crossref, Medline, CAS, Google Scholar12 Karlsson FH, Fak F, Nookaew I et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat. Commun.3,1245 (2012).Crossref, Medline, Google Scholar13 Qin J, Li R, Raes J et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature464(7285),59–65 (2010).Crossref, Medline, CAS, Google Scholar14 Matthan NR, Pencina M, LaRocque JM et al. Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD. J. Lipid Res.50(9),1927–1935 (2009).Crossref, Medline, CAS, Google Scholar15 Rajaratnam RA, Gylling H, Miettinen TA. Cholesterol absorption, synthesis, and fecal output in postmenopausal women with and without coronary artery disease. Arterioscler. Thromb. Vasc. Biol.21(10),1650–1655 (2001).Crossref, Medline, CAS, Google Scholar16 Flint HJ. Obesity and the gut microbiota. J. Clin. Gastroenterol.45(Suppl.),S128–S132 (2011).Crossref, Medline, CAS, Google Scholar17 Bennion LJ, Grundy SM. Effects of obesity and caloric intake on biliary lipid metabolism in man. J. Clin. Invest.56(4),996–1011 (1975).Crossref, Medline, CAS, Google Scholar18 Martinez I, Lattimer JM, Hubach KL et al. Gut microbiome composition is linked to whole grain-induced immunological improvements. ISME J.7,269–280 (2013).Crossref, Medline, CAS, Google Scholar19 Winter SE, Winter MG, Xavier MN et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science339(6120),708–711 (2013).Crossref, Medline, CAS, Google Scholar20 Devkota S, Wang Y, Musch MW et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in IL10-/- mice. Nature487(7405),104–108 (2012).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByGastrointestinal Tract Pathology in a BALB/c Niemann–Pick Disease Type C1 Null Mouse Model22 January 2018 | Digestive Diseases and Sciences, Vol. 63, No. 4Relative variations of gut microbiota in disordered cholesterol metabolism caused by high-cholesterol diet and host genetics28 June 2017 | MicrobiologyOpen, Vol. 6, No. 4 Vol. 8, No. 5 Follow us on social media for the latest updates Metrics Downloaded 125 times History Published online 3 May 2013 Published in print May 2013 Information© Future Medicine LtdKeywordscholesterol metabolismdysbiosisgut microbiotametabolic syndromeFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

682 PREVALENCE OF METABOLIC SYNDROME AMONG MALAYSIAN ADULTS AGED ≥ 30 YEARS ACCORDING TO THE NCEP-ATP III, IDF AND JIS DEFINITIONS

Objective: The objective of this study is to compare the prevalence of Metabolic Syndrome (MetS) as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III)1, International Diabetes Federation (IDF) world-wide definition2 and the ‘harmonised’ definition by the Joint Interim Statement (JIS)3. Methods: A community based cross-sectional study involving 11,288 adults aged ≥ 30 years was conducted in urban and rural areas of Malaysia between 2007 and 2010. Demographic data, waist circumference (WC), blood pressure readings; and fasting venous blood for lipid and glucose assays were obtained. Data was analysed using STATA version 11. Results: Out of the11,288 subjects, 8836 had complete data on all the MetS components and were therefore included in the analysis. Mean age was 53.2 years (SD ± 10.6). The table shows the overall and age-adjusted prevalence of MetS according to the NCEP-ATP III, IDF and JIS definitions by location, gender, ethnicity and education attainment.Conclusions: The JIS definition gave the highest overall prevalence of MetS among Malaysian adults, as well as the age-adjusted prevalence by location, gender, ethnicity and education attainment. The NCEP-ATP III gave the lowest prevalence due to the higher WC cut points. Prevalence was significantly lower in Chinese and Indigenous groups regardless of the criteria used. There was no significant difference in the prevalence between urban and rural population using IDF and JIS definitions. References National Cholesterol Education Program (NCEP)Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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) final report. Circulation 2002; 106: 3143–421. Alberti KG, Zimmet P, Shaw J, International Diabetes Federation (IDF) Epidemiology Task Force Consensus Group. The metabolic syndrome: a new world- wide definition. Lancet 2005; 366: 1059–62. Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome. A Joint Interim Statement (JIS) of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640–5.

Hemodynamics assessed via approximate entropy analysis of impedance cardiography time series: effect of metabolic syndrome

The metabolic syndrome (MS), a predisposing condition for cardiovascular disease, presents disturbances in hemodynamics; impedance cardiography (ICG) can assess these alterations. In subjects with MS, the morphology of the pulses present in the ICG time series is more irregular/complex than in normal subjects. Therefore, the aim of the present study was to quantitatively assess the complexity of ICG times series in 53 patients, with or without MS, through a nonlinear analysis algorithm, the approximate entropy, a method employed in recent years for the study of several biological signals, which provides a scalar index, ApEn. We correlated ApEn computed from ICG times series data during fasting and postprandial phase with the presence of alterations in the parameters defining MS [Adult Treatment Panel (ATP) III (Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C; National Heart, Lung, and Blood Institute; American Heart Association. Circulation 109: 433-438, 2004) and the International Diabetes Federation (IDF) definition]. Results show that ApEn was significantly higher in subjects with MS compared with those without (1.81 ± 0.09 vs. 1.65 ± 0.13; means ± SD; P = 0.0013, with ATP III definition; 1.82 ± 0.09 vs. 1.67 ± 0.12; P = 0.00006, with the IDF definition). We also demonstrated that ApEn increase parallels the number of components of MS. ApEn was then correlated to each MS component: mean ApEn values of subjects belonging to the first and fourth quartiles of the distribution of MS parameters were statistically different for all parameters but HDL cholesterol. No difference was observed between ApEn values evaluated in fasting and postprandial states. In conclusion, we identified that MS is characterized by an increased complexity of ICG signals: this may have a prognostic relevance in subjects with this condition.

Clinical course of patients with chronic systolic heart failure due to the association of Chagas disease and systemic arterial hypertension

rosuvastatin on coronary atheroma in stable coronary artery disease: multicenter coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS). Circ J 2009;73:2110–7. [5] Smith Jr SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006;113:2363–72. [6] 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) final report. Circulation 2002;106:3143–421. [7] Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227–39. [8] Deedwania P, Singh V, Davidson MH. Low high-density lipoprotein cholesterol and increased cardiovascular disease risk: an analysis of statin clinical trials. Am J Cardiol 2009;104:3E–9E. [9] Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007;357:1301–10. [10] Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. Highdensity lipoprotein cholesterol and cardiovascular disease: Four prospectiveAmerican studies. Circulation 1989;79:8–15. [11] Shewan LG, Coats AJ. Ethics authorship publishing scientific articles Int J Cardiol 2010;144:1–2.

Increased Coronary Heart Disease Risk Determined by High High-Density Lipoprotein Cholesterol and C-Reactive Protein: Modulation by Variation in the CETP Gene

Epidemiological evidence strongly favors the notion that the risk of cardiovascular disease (CVD) is inversely related to the plasma high-density lipoprotein (HDL) cholesterol concentration.1 Low HDL cholesterol is still predictive of high CVD risk in subjects with low LDL cholesterol,2 as well as during statin treatment.3 These observational data and other studies, which show that HDL particles contain a large number of antioxidative, antiinflammatory, and antiproliferative proteins, underlie the generally held view that HDL particles have atheroprotective properties.1–5 However, evidence is accumulating supporting the concept that high HDL cholesterol levels do not always predict reduced CVD risk. The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) trial and the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk case-control study revealed that (recurrent) CVD risk is not decreased in subjects with the highest HDL cholesterol and the greatest mean HDL particle size.6 More recently, a high HDL cholesterol, high C-reactive protein (CRP) subgroup of individuals at increased risk for a first cardiovascular event was identified in the community-dwelling Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort using the “outcome event mapping approach,” a graphical exploratory data analysis tool that has been originally developed by Corsetti et al.7 Applying this analytic method to the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction cohort, the presence of a subgroup …

Cardiovascular and Overall Mortality Risk in Relation to Alcohol Consumption in Patients With Cardiovascular Disease

Alcohol, in striking contrast to tobacco and illicit drugs, is linked to an extensively documented J-shaped dose-effect curve, with regular moderate consumption reducing cardiovascular and overall mortality,1 whereas excessive or binge drinking has the opposite effect.1,2 Data indicative of a lower risk of cardiovascular events among moderate drinkers in apparently healthy people are extensive and consistent, whereas the role of alcohol intake among patients with cardiovascular disease (CVD) is less clear.3 Among the factors that contribute to prevention in survivors of primary cardiovascular events, lifestyle and dietary habits play a major role. However, guidelines in this area are based either on studies of apparently healthy subjects or on a few studies of cardiovascular patients.4,5 In particular, recommendations about alcohol consumption in patients with previous CVD reflect experts’ consensus rather than circumstantial evidence.3,6 The US Food and Drug Administration warns that heart disease patients should stop drinking, and people who take aspirin regularly should not drink alcohol.7 However, in the American Heart Association/American College of Cardiology guidelines for secondary prevention,5 CVD patients are encouraged to maintain a lifestyle that includes drinking alcohol in moderation. The “Diet and Lifestyle Recommendations” scientific statement from the American Heart Association Nutrition Committee8 advises, “If you consume alcohol, do so in moderation (equivalent of no more than 1 drink in women or 2 drinks in men per day).” The latter statement is largely accepted within the scientific community, definitely when referring to healthy people, although some would advise people to abstain completely rather than encouraging them to drink small amounts regularly. It has in fact been suggested that the consumption of alcohol for certain health benefits should not be encouraged, because the harm would far outweigh the gain, especially among poor populations and in low-income countries, where the …

Improving the Pathway From Cardiovascular Medication Prescribing to Longer-Term Adherence

tion, and Treatment of High Blood Pressure (JNC 7) recommendations and an equal proportion of patients eligible for aspirin based on American Heart Association (AHA) guidelines were not receiving these therapies. Although the study time period overlapped with the publication dates of these guidelines, basic recommendations for primary prevention have not changed dramatically for many years, and therefore the results of Nasir et al are very consistent with the existing literature about missed opportunities for prevention. This study also demonstrates the somewhat fine balance between “underuse” and “overuse” of medical therapies and thus has implications for efforts to improve health care quality. As expected, the use of primary prevention increased over time in patients who were considered appropriate candidates for treatment. However, after receiving CACS results, a substantial proportion of patients for whom guidelines do not recommend therapy were also started on these treatments.

Polyphenols and Cholesterol Efflux

Despite strong evidence for an inverse association between high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular risk,1 successful therapeutic strategies to target HDL have remained elusive. A recent Phase III clinical trial failed to show clinical benefit with the cholesteryl ester transfer protein inhibitor torcetrapib despite markedly increased HDL-C levels.2,3 This outcome reinforced a growing consensus that measurement of HDL-C alone may be an incomplete surrogate for the in vivo functionality of HDL and the clinical efficacy of targeting HDL. The careful mechanistic assessment of HDL function has thus emerged as a potential way forward.4 Macrophage reverse cholesterol transport (RCT), the process by which cholesterol is transported from macrophage “foam” cells to the liver for ultimate fecal excretion, has been postulated to play a major role in HDL-mediated atheroprotection.5 Indeed, quantitative measures of macrophage RCT are more strongly associated with atherosclerosis than plasma HDL-C concentrations in mice.6 The first critical step of macrophage RCT involves efflux of cellular cholesterol to circulating HDL particles. Research in recent years has documented a specific role for the macrophage transporters ATP-binding cassette subfamilies A1 and G1 (ABCA1 and ABCG1) in cholesterol efflux (see the Figure). These findings have stimulated efforts to target the macrophage at the cellular level as a means of enhancing overall RCT. For example, pharmacological agonism of the liver X receptor (LXR) upregulates both ABCA1 and ABCG1 expression,7,8 promotes macrophage cholesterol efflux ex vivo and RCT in vivo, …

Broadening Our Understanding of Survival After Myocardial Infarction

As clinicians and scientists, it is common to presume that clinical outcomes after myocardial infarction (MI) are most profoundly influenced by the pathogenesis of the disease itself, including genetics, cardiovascular risk factors, inflammatory state, disease severity (eg, the number and severity of obstructed coronary arteries), and the treatments that we offer. Consequently, our efforts to optimize the outcomes of our patients are aimed at following clinical guidelines in care for individual patients.1–3 When our profession seeks to influence systems of care and public policy, our focus has been on increasing access to lifesaving therapies.4 Because they appear outside of physicians’ locus of control, risk factors related to patients’ socioeconomic status are often not considered targets for intervention. Article see p 375 Although numerous studies have defined an adverse association between lower socioeconomic status and post-MI treatment5 and outcomes,6–8 little work has been done to develop interventions to overcome these disparities. We also have not sought to systematically understand mediating factors that may influence the prognostic associations of socioeconomic risk factors with outcomes. The reasons there have been such little progress in overcoming socioeconomic status barriers, despite the national priorities to create equity in health care,9–11 are multifactorial and include both the difficulties in measuring socioeconomic status and the challenges in overcoming them. In a critical review of the science linking socioeconomic status to health outcomes, Braveman and colleagues12 demonstrated that different measures of socioeconomic status are not interchangeable, …

The SHAPE Paradigm

Atherosclerosis is a chronic immunoinflammatory disease trigerred by lipoprotein retention in the subendothelium and produces its most serious manifestations by triggering arterial thrombosis when the plaque ruptures or erodes.1 Atherothrombotic cardiovascular disease remains the leading cause of death in the West and is achieving similar dubious distinction in developing countries.2 Atherosclerosis begins at a young age, but it remains clinically silent for a long time and the majority of clinical manifestations occur later in life. Despite considerable progress, regrettably 50% of life-threatening acute cardiovascular events occur in previously asymptomatic individuals. Identifying individuals at risk for future cardiovascular events affords an opportunity for risk reduction and thus remains a major imperative for healthcare professionals. In 2006 the SHAPE (Society for Heart Attack Prevention and Education) Task Force introduced an algorithm incorporating noninvasive screening for subclinical atherosclerosis to augment risk factor–based risk stratification in asymptomatic subjects between the ages of 45 to 75 in men and 55 to 75 in women, excluding those at very low risk or at high risk.3 In June 2009, the Texas Governor Rick Perry signed off on the Texas Heart Attack Prevention Bill introduced by Rep Rene Oliveira, mandating health-benefit plans to cover noninvasive screening for subclinical atherosclerosis. This bill grew out of the 2006 SHAPE Task Force guidelines and became effective September 1, 2009; an earlier version of the bill had been rejected in 2007. This generated a mixed reaction from healthcare professionals and others, much of which played out in the media. The critics argued that such an action is inappropriate because: (1) the SHAPE guidelines were created by an ad hoc group and had not been explicitly endorsed by the American College of Cardiology (ACC) or the American Heart Association (AHA), and (2) SHAPE guidelines are not based on randomized clinical …

Improving Lipid Goal Attainment

Improving Lipid Goal Attainment

Medicine Should Be More Like Missouri

Missouri is the “Show Me” State. Although the origins of the term are uncertain, it seems that it might have been etched into the national consciousness during a speech by U.S. Congressman Willard Duncan Vandiver. In an 1899 speech he stated, “I come from a state that raises corn and cotton and cockleburs and Democrats, and frothy eloquence neither convinces nor satisfies me. I am from Missouri. You have got to show me.”1 The “Show Me” spirit is sometimes lacking in the field of Medicine, where we seem intent on integrating new tests and procedures before they are thoroughly vetted. Although we bemoan the slow adoption of effective treatments, we often prematurely adopt unproven strategies. Our quality measures are focused on underuse—the missed opportunity to provide a strongly indicated test or treatment. National registries, often industry-sponsored, also are commonly oriented toward addressing undertreatment, further fueling a national preoccupation on having not done enough rather than on having done too much. It is true that this emphasis on undertreatment has improved quality of care. In the mid-1990s, for example, only about half of the patients nationally, and in several states only about one-third, who were ideal candidates for β-blocker therapy after having survived an acute myocardial infarction were prescribed the medication. Ideal candidates were identified by careful chart reviews that determined a group with no documented absolute or relative contraindications.2 This pattern of care was described almost 15 years after clinical trials provided evidence of the benefit. Moreover, those who were treated had better survival, concordant with what would be expected based on the trials. Studies that revealed similarly stark patterns for the prescription of aspirin and angiotensin converting-enzyme inhibitors2–5 led to quality measures that tracked undertreatment, …

Improving Weight Loss in Cardiac Rehabilitation

In the current issue of Circulation , Philip Ades and his associates at the University of Vermont College of Medicine have provided us with an innovative and important article demonstrating the feasibility and benefits of an enhanced exercise option in cardiac rehabilitation.1 In this study, 74 patients were randomized to a standard cardiac rehabilitation exercise program versus a high-calorie-expenditure exercise program. All patients were provided with 16 hours of group dietary counseling and given a dietary target deficit of 500 calories per day. One group was given a standard exercise program typically used in cardiac rehabilitation (25 to 40 minutes, 3 times per week) and the other an enhanced program targeting 45 to 60 minutes, 5 to 7 times per week, or a total caloric expenditure of 3000 to 3500 kcal/week. The length of the intervention was 5 months, though 1-year data collection was also performed. Patients were of course followed up closely to promote compliance. Article see p 2671 The primary outcome of the study was weight loss. Subjects in the high-calorie-expenditure exercise program lost more than twice as much total body weight (8.2±4 versus 3.7±5 kg) and fat mass (5.9±4 versus 2.8±3 kg). Waist circumference also decreased by a greater amount (7±5 versus 5±5 cm). The enhanced exercise program was also associated with a greater benefit on a number of coronary risk factors including insulin resistance, total/high-density lipoprotein cholesterol ratio, and metabolic syndrome. Most of the weight loss and the difference between the groups were retained at 1-year, though some weight regain occurred (1.3 kg for the enhanced exercise group and 0.9 kg for the standard exercise group). Guidelines for the secondary prevention of coronary heart disease2 and for management of specific coronary risk factors3–4 emphasize the importance of lifestyle change, including weight loss, but …

The Complex Relationship Between Cholesterol and Brain Hemorrhage

In this issue of Circulation , Noda et al1 report an association between low levels of low-density lipoprotein cholesterol (LDL-C) and an increase in the risk of fatal intraparenchymal intracerebral hemorrhage in a Japanese population-based cohort. The relationship between lipid levels and stroke is complex. The Prospective Studies Collaboration conducted a meta-analysis evaluating the association between blood cholesterol and vascular mortality based on data from 61 prospective cohort studies including nearly 900 000 persons free of vascular disease at baseline (11.6 million person-years at risk).2 Lower levels of usual total cholesterol were strongly associated with lower risk of fatal ischemic heart disease; every 1 mmol/L lower cholesterol was associated with a 56% reduction (hazard ratio [HR], 0.44; 95% CI, 0.42 to 0.48) in those 40 to 49 years of age, a 34% reduction (HR, 0.66; 95% CI, 0.65 to 0.68) in those 50 to 69 years of age, and a 17% reduction (HR, 0.83; 95% CI, 0.81 to 0.85) in those 70 to 89 years of age. In contrast to death resulting from ischemic heart disease, there was only a weak relationship between usual total cholesterol and death caused by stroke in those 40 to 59 years of age (HR, 0.90; 95% CI, 0.84 to 0.97 for every 1 mmol/L lower cholesterol) and no relationship for older age groups after accounting for blood pressure. An analysis combing the data for the Prospective Studies Collaboration with data from the Multiple Risk Factors Intervention Trial (MRFIT) also found that lower usual total cholesterol was associated with a lower risk of fatal stroke in those 40 to 49 years of age (HR, 0.87; 95% CI, 0.76 to 1.00 per 1 mmol/L lower total cholesterol), with similar reductions in those 50 to 59 (HR, 0.91; 95% CI, 0.85 to 0.97) and 60 …

Low-Density Lipoprotein Cholesterol Reduction and Prevention of Cardiovascular Disease

Low-Density Lipoprotein Cholesterol Reduction and Prevention of Cardiovascular Disease

Questioning Conventional Wisdom

In science, what seems obvious may not be true, and what is accepted as conventional wisdom, may sometimes be based on flawed assumptions. What is more obvious than the fact that the sun revolves around the earth? Each day the sun rises in the eastern horizon, and we observe it moving across the sky until it retires in the west. And yet, it is not true that the earth is the center of the universe. Galileo de’ Galilei, the scientist born in Pisa, was persecuted for questioning such conventional wisdom and supporting the theory proposed by Nicolaus Copernicus of a heliocentric universe. Ultimately, the truth could not be suppressed. We have many examples of progress that resulted from the questioning of strongly held beliefs that once seemed so obvious. Who anticipated that a gastric ulcer could be considered an infectious disease?1 Who expected that drugs that effectively suppressed premature ventricular beats in patients with ischemic heart disease would cause harm?2 Who believed that treatment strategies associated with substantial risk reduction might be poorly adopted into practice even 10 years after the publication of the trials establishing their efficacy?3 Who could …