Preventable Coronary Heart Disease Events from Control of Cardiovascular Risk Factors in US Adults With Diabetes (Projections from Utilizing the UKPDS Risk Engine)
2014; Elsevier BV; Volume: 113; Issue: 8 Linguagem: Inglês
10.1016/j.amjcard.2013.12.042
ISSN1879-1913
AutoresNathan D. Wong, Christopher Patao, Shaista Malik, Uchenna H. Iloeje,
Tópico(s)Cardiovascular Function and Risk Factors
ResumoType 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged ≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal. Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged ≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal. The relation of type 2 diabetes mellitus (T2DM) to increased risk for coronary heart disease (CHD) events and mortality is well established.1Kannel W.B. McGee D.L. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study.Diabetes Care. 1979; 2: 120-126Crossref PubMed Scopus (1022) Google Scholar, 2Malik S. Wong N.D. Franklin S.S. Kamath T.V. L'Italien G.J. Pio J.R. Williams R. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States Adults.Circulation. 2004; 110: 1239-1244Crossref Scopus (1440) Google Scholar, 3American Diabetes Association Economic costs of diabetes in the US in 2007.Diabetes Care. 2008; 31: 596Crossref PubMed Scopus (1369) Google Scholar Recent data show among US adults with T2DM 50%,5Gaede P. Lund-Anderson H. Parving H.H. Pedersen O. Effect of a multiple intervention on mortality in type 2 diabetes.N Engl J Med. 2008; 358: 580-591Crossref PubMed Scopus (2885) Google Scholar recent trials of intensive glycemic and blood pressure control have shown less dramatic findings.6The Action to Control Cardiovascular Risk in Diabetes Study Group Effects of intensive glucose lowering in type 2 diabetes.N Engl J Med. 2008; 358: 2545-2559Crossref PubMed Scopus (6683) Google Scholar, 7Patel A. MacMahon S. Chalmers J. Neal B. Billot L. Woodward M. Marre M. Cooper M. Glasziou P. Grobbee D. Hamet P. Harrap S. Heller S. Liu L. Mancia G. Mogensen C.E. Pan C. Poulter N. Rodgers A. Williams B. Bompoint S. de Galan B.E. Joshi R. Travert F. ADVANCE Collaborative GroupIntensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N Engl J Med. 2008; 358: 2560-2572Crossref PubMed Scopus (6180) Google Scholar, 8The ACCORD Study Group Effects of intensive blood-pressure control in type 2 diabetes mellitus.N Engl J Med. 2010; 362: 1575-1585Crossref PubMed Scopus (2864) Google Scholar In this report, we examine the estimated impact of achieving glucose, blood pressure, smoking, and lipid control in a population-representative cohort of adults with T2DM on CHD events utilizing projections based on the United Kingdom Prospective Diabetes Study (UKPDS) Risk Engine.9Stevens R.J. Kothari V. Alder A.I. Stratton I.M. United Kingdom Prospective Diabetes Study (UKPDS) Group The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56).Clin Sci. 2001; 101: 671-679Crossref PubMed Scopus (1034) Google Scholar We estimate the population-wide impact on achieving control of individual and composite risk factor control on CHD events. We identified all adults aged ≥30 years with T2DM using the cross-sectional National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. In our study, T2DM was defined as those who were aged 30 years and older when first told they had diabetes, as has been used in previous NHANES studies as a cut point for the diagnosis of T2DM.10Wong N.D. Glovaci D. Wong K. Malik S. Franklin S.S. Wygant G. Iloeje U. Global cardiovascular disease risk assessment in United States adults with diabetes.Diab Vas Dis Res. 2012; 9: 146-152Crossref PubMed Scopus (54) Google Scholar, 11Koopman R.J. Mainous 3rd, A.G. Diaz V.A. Geesey M.E. Changes in age at diagnosis of type 2 diabetes mellitus in the United States, 1988 to 2000.Ann Fam Med. 2005; 3: 60-63Crossref PubMed Scopus (208) Google Scholar Diabetes duration was calculated by subtracting the participant's age at survey from their age when first told they had diabetes. The sample population was then restricted to persons who had information on age, gender, blood pressure, HbA1c, high-density lipoprotein cholesterol (HDL-C), and triglycerides and were free of any known clinical CVD defined as answering no to the survey questions asking whether they were told by their doctor if they ever had CHD, heart attack, stroke, or heart failure. The UKPDS Risk Engine9Stevens R.J. Kothari V. Alder A.I. Stratton I.M. United Kingdom Prospective Diabetes Study (UKPDS) Group The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56).Clin Sci. 2001; 101: 671-679Crossref PubMed Scopus (1034) Google Scholar includes age, sex, HbA1c, diabetes duration, smoking status, total/HDL-C ratio, systolic blood pressure, and ethnicity and calculates the 10-year probability of developing a CHD event. Diabetes duration is defined as the number of years because a person was told they first had diabetes. Smoking status is defined by whether a person never smoked, previously smoked but has since stopped (past smoker), or continues to smoke (current smoker). In terms of other risk factors, HbA1c, systolic blood pressure, total cholesterol, and HDL-C are used to calculate risk. HbA1c was measured using high-performance liquid chromatography. Systolic blood pressure measurements were taken using a mercury sphygmomanometer and then averaged up to 4 measurements. Total cholesterol was measured enzymatically after hydrolyzation and oxidation. HDL-C was measured using a direct immunoassay technique. Detailed explanations to specimen analysis and data collection are discussed in the Laboratory Procedures Manual.12NHANESLaboratory Procedures Manual. US Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville, MD2007-2008Google Scholar The SI equivalent of goal levels was calculated as follows: cholesterol (mg/dl) × 0.0259 = cholesterol (mmol/L); (HbA1c (%) − 2.15) × 10.929 = HbA1c (mmol/mol). These values were then rounded to the nearest tenth. Goal or recommended levels were defined based on adapting the American Diabetes Association guidelines13American Diabetes Association Standards of Medical Care in diabetes 2007.Diabetes Care. 2007; 30: S4-S41Crossref PubMed Scopus (1536) Google Scholar for diabetes care relevant for our survey period: HbA1c <7% (53 mmol/mol), systolic blood pressure <130 mm Hg, and HDL-C ≥1.036 mmol/L (40 mg/dl) in men and ≥1.3 (1.295) mmol/L (50 mg/dl) in women. A total cholesterol level of <4.403 mmol/L (170 mg/dl) was based on the approximate equivalent of the LDL-C goal of 2.59 mmol/L (100 mg/dl). The recommended HDL-C cut points are also consistent for persons with metabolic syndrome.14Grundy S.M. Cleeman J.I. Daniels S.R. Donato K.A. Eckel R.H. Franklin B.A. Gordon D.J. Krauss R.M. Savage P.J. Smith Jr., S.C. Spertus J.A. Costa F. American Heart AssociationNational Heart, Lung, and Blood InstituteDiagnosis and management of the metabolic syndrome: an American Heart Association/National Heart Lung and Blood Institute Scientific Statement.Circulation. 2005; 112: 2735-2752Crossref PubMed Scopus (9387) Google Scholar A subanalysis also examined the impact of a blood pressure goal of <140/80 mm Hg that has been recently recommended by European and US societies. NHANES identifies 3 specific ethnicities, non-Hispanic white, non-Hispanic black, and Mexican American, and an "other" category, whereas UKPDS identifies 3 different ethnicities, white, Afro-Caribbean, and Asian-Indian. In our study, those identified as non-Hispanic black within NHANES were classified as Afro-Caribbean in the UKPDS Risk Engine and non-Hispanic white, Mexican American, and other were classified as white. To examine the significance of varying levels of risk factor control, 3 risk factor control scenarios were established: (1) "All to Goal" control was defined as controlling all current smokers to past smokers and setting risk factor levels to minimum goal levels (as previously mentioned) in all subjects who were not already at control; (2) "Nominal Control" was defined as controlling all current smokers to past smokers, an absolute level reduction of 1% HbA1c (7.6 mmol/mol), 10% relative reduction in systolic blood pressure, 10% relative increase in HDL-C, and a 25% relative reduction of total cholesterol in those who had a respective risk factor above the goal level; and (3) "Aggressive Control" was defined as controlling all current smokers to past smokers, an absolute level reduction of 2% HbA1c (15.2 mmol/mol), a 20% relative reduction of systolic blood pressure, a 20% relative increase in HDL-C, and a 50% relative reduction of total cholesterol, for those who did meet the goal level of their respective risk factor. Just as in "All to Goal" control, only subjects not already at goal were "treated" in the "Nominal" and "Aggressive" control scenarios. Additionally, HbA1c levels could go below the target of 7% (53 mmol/mol) but by programing lower limits were not allowed to go below 6.5% (48 mmol/mol) in any subject in these 2 scenarios. The sample population was compiled using SAS 9.1 and exported to the UKPDS spreadsheet allowing for estimation of 10-year myocardial infarction risk. An uncontrolled 10-year probability was calculated for each individual using the initial risk profile. That probability was then multiplied by the NHANES 6-year survey weighted sample size to calculate the number of events in 10 years. Estimates were stratified by gender and by 3 age groups beginning at 30 years of age: <45, 45 to 65, and ≥65 years. The weighted sample size was calculated by multiplying diagnosed diabetes prevalence by its appropriate population total from the US Current Population Surveys. Individual risk factors were examined for attainment of goal levels. If an individual was at goal for a specific risk factor, their level was left untouched. If an individual was not at goal, a new value was calculated based off their initial level and the control scenario described previously. Both the relative risk reduction and the absolute risk reduction (ARR) were calculated as the proportion of expected events over 10 years that would be prevented by the risk factor control scenario and the difference between the original and control absolute risk, respectively. After applying the new control levels, a new 10-year risk and number of events were calculated. The number of events was subtracted from the number of events at baseline to calculate the number of projected preventable events. The percent of projected preventable events was calculated by dividing the number of controlled events by the number of uncontrolled events and then subtracting that number from one. For composite analysis, all risk factors were examined and calculated by the level of control being examined. Finally, given the potential for misclassification of rate, we conducted sensitivity analyses for race by recalculating estimates setting all participants to Afro-Caribbean. Of 14,242 adults aged ≥30 years in our sample (representing 177.8 million) from NHANES 2007 to 2012, 9.6% or 1,920 were told they had diabetes. Of these 1,379 (72.8%) were without previous CVD, and 1,209 (88.9%) had complete risk factor information and were included in our analysis; this represented 12.4 million persons with diagnosed T2DM. Table 1 lists means or prevalences of the key risk factors included in the UKPDS model between men and women in our sample. There was little difference by gender, except for greater current and former smokers (p <0.05) and lower levels (p <0.01) of total and HDL-C among men compared with women. With the existing risk factor profile among our sample of US adults with T2DM, the average 10-year CHD risk is 16.5% with a predicted 2.0 million CHD events, 1.3 million in men and 0.7 million in women, with risk approximately double in men, compared with women (Tables 2 and 3).Table 1Weighted means/prevalence of cardiovascular risk factors for men and women with T2DMRisk Factors (p value), n = 1,209 (n = 12.4 million [M])Menn = 606Womenn = 603Proportion (%)Proportion (%)Afro-Carribean (351, 2.1 M)14.719.3Nonsmokers (628, 5.5 M)42.7∗p <0.05 between men and women across all smoking categories.56.8Smokers (186, 1.8 M)17.5∗p <0.05 between men and women across all smoking categories.15.0Previous smokers (395, 3.8 M)39.8∗p <0.05 between men and women across all smoking categories.28.2Lower 95% CIMeanUpper 95% CILower 95% CIMeanUpper 95% CIAge (yrs)58.359.761.158.759.960.1Diabetes duration (yrs)8.08.89.77.88.69.3Systolic blood pressure (mm Hg)126.4129131.7127.6129.3131HbA1c (%)7.17.37.57.047.27.3Total cholesterol, mmol/L (mg/dl)4.4 (171.5)4.6 (176.1)†p <0.0005 between men and women.4.7 (180.7)4.84 (186.1)4.9 (191.2)5.1 (196.2)HDL-C, mmol/L (mg/dl)1.11 (43.0)1.14 (44.1)†p <0.0005 between men and women.1.2 (45.3)12.2 (48.0)1.3 (49.6)1.3 (51.3)CI = confidence interval.∗ p <0.05 between men and women across all smoking categories.† p <0.0005 between men and women. Open table in a new tab Table 2Ten-year CHD risk, number of expected CHD events, and proportion of CHD events prevented for US Adults with T2DM controlled to goal risk factor levelsn = 1,209 (n = 12.4 million)UncontrolledSmokingHbA1cSystolic Blood PressureTotal CholesterolHDL-CAll Risk Factors10-yr Risk (%)Exp. CHD (M)10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events PreventedOverall (12.4 M)16.52.0415.93.6714.611.6315.46.7214.213.6615.09.3310.238.28 Men (6.15 M)21.71.3320.84.1219.211.5420.55.5519.111.7120.26.9014.134.76 65 (2.15 M)29.40.6328.62.5427.36.9327.85.4727.37.0727.85.3321.925.45 Women (6.25 M)11.30.7111.02.7910.011.7910.39.009.317.439.714.006.245.07 65 (2.21 M)16.40.3616.21.4615.08.7714.610.8313.915.4014.412.009.641.18Goal risk factor control defined as all current smokers to past smokers, HbA1c ≤7%, systolic blood pressure ≤130 mm Hg, total cholesterol ≤4.4 mmol/L (170 mg/dl), and HDL-C ≥1.0 mmol/L (40 mg/dl) in men and ≥1.3 mmol/L (50 mg/dl) in women. Open table in a new tab Table 3Ten-year risk, number of expected events, and proportion of prevented events for T2DM adults after aggressive risk factor controln = 1,209UncontrolledSmokingHbA1cSBPTotal CholesterolHDL-CAll Risk Factors10-yr Risk (%)Exp. CHD (M)10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events Prevented10-yr Risk (%)% Events PreventedOverall (12.4 M)16.52.0415.93.6714.810.3714.810.1810.735.0515.18.457.554.79 Men (6.15 M)21.71.3320.84.1219.510.1719.79.3112.243.4920.26.6710.651.30 65 (2.15 M)29.40.6328.62.5427.27.3326.59.6222.224.5527.75.5716.743.13 Women (6.25 M)11.30.7111.02.7910.110.7710.011.856.641.1810.011.894.461.47 65 (2.21 M)16.40.3616.21.4614.99.1614.213.3810.238.0014.610.866.858.59Aggressive risk factor control defined as all current smokers to past smokers, 2% absolute reduction of HbA1C with 6.5% reduction cap, 20% relative reduction of SBP, 50% relative reduction of total cholesterol, and 20% relative increase of HDL-C.SBP = systolic blood pressure. Open table in a new tab CI = confidence interval. Goal risk factor control defined as all current smokers to past smokers, HbA1c ≤7%, systolic blood pressure ≤130 mm Hg, total cholesterol ≤4.4 mmol/L (170 mg/dl), and HDL-C ≥1.0 mmol/L (40 mg/dl) in men and ≥1.3 mmol/L (50 mg/dl) in women. Aggressive risk factor control defined as all current smokers to past smokers, 2% absolute reduction of HbA1C with 6.5% reduction cap, 20% relative reduction of SBP, 50% relative reduction of total cholesterol, and 20% relative increase of HDL-C. SBP = systolic blood pressure. Table 2 and Figure 1 examine the effects of controlling risk factors to goal levels in all subjects not already at goal (All to Goal control). The proportion of CHD events estimated to be preventable from HbA1c control to goal was 11.6% overall (1.9% ARR) but ranged from 6.9% (2.1% ARR) in men aged 65 years and over to 31.8% (2.6% ARR) in men <45 years of age. Controlling total cholesterol to goal had the largest impact on preventing CHD events, 13.7% (2.3% ARR) overall and ranging from 7.1% (2.1% ARR) in men aged 65 years and over to 23.4% (1.9% ARR) in men aged <45 years. Overall impacts from control of smoking, systolic blood pressure, or HDL-C were less but varied according to the age group, gender, and race. When controlling for all risk factors to goal levels, among all those with T2DM, 10-year CHD risk was reduced from 16.5% to 10.2%, or an ARR of 6.3% and an estimated 38.3% of CHD events prevented. This ranged from 25.5% (7.5% ARR) in men aged 65 years and over to 57.5% (4.7% ARR) in men aged <45 years. When testing the effect of the recently revised systolic blood pressure goal of <140 mm Hg, the proportion of CHD events preventable is reduced from 6.7% to 4.0%, and when included in all risk factor control, it is reduced from 38.3% to 36.3%. Nominal control of smoking, HbA1c, systolic blood pressure, total cholesterol, and HDL-cholesterol resulted in estimated proportions of CHD events prevented of 3.7% (ARR = 0.6%), 6.6% (ARR = 1.1%), 5.3% (ARR = 0.9%), 17.5% (ARR = 2.9%), and 8.7% (ARR = 1.4%; Figure 1). Controlling for all risk factors to nominal levels brought overall 10-year risk down to 10.4% (6.1% ARR), resulting in an estimated 36.7% of events prevented, which varied from 30.8% (9.1% ARR) in men aged 65 years and over to 48.7% (1.9% ARR) in women aged <45 years. Table 3 and Figure 1 show the potential effects of aggressive risk factor control. Aggressive control of HbA1c was projected to prevent 10.4% (1.7% ARR) of CHD events overall, systolic blood pressure 10.2% (1.7% ARR) of events, smoking 3.7% (0.6% ARR) of events, and HDL-C 8.5% (1.4% ARR) of events. Control of total cholesterol resulted in the greatest proportion of estimated preventable events among all the risk factors examined: 35.1% (5.8% ARR) of events were projected to be preventable. Aggressive control of all risk factors produced a 7.5% 10-year risk of CHD or projected prevention of 54.8% (8% ARR) of all events. The largest reduction in CHD events was seen among women aged <45 years who had a 71.6% relative risk reduction (2.8% ARR). Finally, we conducted sensitivity analyses to show the effect of resetting race to all Afro-Caribbean or all white. The race sensitivity analysis shows little difference in the proportion of events preventable for white versus Afro-Caribbean from all risk factor controls to nominal levels (36.5% vs 39.5%, respectively) or aggressive control levels (54.5% vs 57.4%, respectively), but a modest difference when setting all to goal levels (26.7% vs 41.1%, respectively). CVD is the primary cause of death in about 2/3 of deaths among those with T2DM.3American Diabetes Association Economic costs of diabetes in the US in 2007.Diabetes Care. 2008; 31: 596Crossref PubMed Scopus (1369) Google Scholar Many persons with T2DM remain inadequately controlled for individual risk factors, and until recently, only 1 in 10 were at goal for HbA1c, blood pressure, and lipids.4Wong K. Glovaci D. Malik S. Franklin S.S. Wygant G. Iloeje U. Kan H. Wong N.D. Comparison of demographic factors and cardiovascular risk factor control among US adults with type 2 diabetes by insulin treatment classification.J Diabetes Complications. 2012; 26: 169-174Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Among US adults with T2DM, if risk factors and treatment are left at current levels, approximately 2.0 million CHD events could be expected to occur over the next 10 years. If we are able to control to goal or recommended levels, those not at goal for HbA1c, systolic blood pressure, smoking, total cholesterol, and HDL-C, more than a third (38%) or over to 700,000 CHD events would be projected to be prevented over a 10-year period. More intensive control of these risk factors, however, could prevent as much as 55% of expected CHD events over 10 years, which are approximately 1.1 million CHD events. This is consistent with the 53% risk reduction that was observed in the Steno-2 study involving intensive therapy of subjects with T2DM for HbA1c, blood pressure, and lipids.5Gaede P. Lund-Anderson H. Parving H.H. Pedersen O. Effect of a multiple intervention on mortality in type 2 diabetes.N Engl J Med. 2008; 358: 580-591Crossref PubMed Scopus (2885) Google Scholar Moreover, others have shown among T2DM that achievement of 2 or more targets (among HbA1c, blood pressure, or LDL-C) can result in a 31% reduced risk of CHD over nearly 6 years of follow-up.15Kong A.P. Yang X. Go G.T. So W.Y. Chan W.B. Ma R.C. Ng V.W. Chow C.C. Cockram C.S. Tong P.C. Wong V. Chan J.C. Effects of treatment targets on subsequent cardiovascular events in Chinese patients with type 2 diabetes.Diabetes Care. 2007; 30: 953-959Crossref PubMed Scopus (46) Google Scholar Importantly, although overall half of US persons with diabetes have been recently shown to achieve individual targets for LDL-C, blood pressure, and HbA1c, achievement of goal for the composite of these 3 targets is seen in only 1/4 of patients, stressing the importance of systematic efforts to ensure all DM risk factors are continuously monitored and treated according to the standards of care.16Wong N.D. Patao C. Wong K. Malik S. Franklin S.S. Iloeje U. Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999-2010: comparison by prevalent cardiovascular disease status.Diab Vasc Dis Res. 2013; 10: 505-513Crossref PubMed Scopus (72) Google Scholar Our study represents the first estimation of the US population-wide impact on CHD event reduction from achieving goal (or more nominal or intensive) control of CHD risk factors among a contemporary cohort of adult-free living subjects with T2DM. Assessment of CHD risk using global risk scores such as those from the Framingham Heart Study has been recommended for more than a decade for the purposes of risk stratification in lipid-lowering treatment17NCEP Expert Panel 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: 2486-2497Crossref PubMed Scopus (24729) Google Scholar and more recently as an initial step for cardiovascular risk assessment in asymptomatic adults in general.18Greenland P. Alpert J. Beller G.A. Benjamin E.J. Budoff M.J. Fayad Z.A. Foster E. Hlatky M.A. Hodgson J.M. Kushner F.G. Lauer M.S. Shaw L.J. Smith Jr., S.C. Taylor A.J. Weintraub W.S. Wenger N.K. Jacobs A.K. Smith Jr., S.C. Anderson J.L. Albert N. Buller C.E. Creager M.A. Ettinger S.M. Guyton R.A. Halperin J.L. Hochman J.S. Kushner F.G. Nishimura R. Ohman E.M. Page R.L. Stevenson W.G. Tarkington L.G. Yancy C.W. American College of Cardiology FoundationAmerican Heart Association2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults.JACC. 2010; 56: 2182-2199Abstract Full Text Full Text PDF Scopus (136) Google Scholar The use of global risk assessment among persons with metabolic syndrome and diabetes can be supported by the fact that there is wide heterogeneity of calculated CHD risk among those with metabolic syndrome19Hoang K. Ghandehari H. Lopez V.A. Barboza M.G. Wong N.D. Global coronary heart disease risk assessment of individuals with the metabolic syndrome in the U.S.Diabetes Care. 2008; 31: 1405-1409Crossref PubMed Scopus (35) Google Scholar and among those with diabetes.10Wong N.D. Glovaci D. Wong K. Malik S. Franklin S.S. Wygant G. Iloeje U. Global cardiovascular disease risk assessment in United States adults with diabetes.Diab Vas Dis Res. 2012; 9: 146-152Crossref PubMed Scopus (54) Google Scholar Among US adults with metabolic syndrome (without diabetes) in a much earlier cohort (NHANES 1988 to 1994) using similar methodology as in the present report, we projected that control of LDL-C, HDL-C, and blood pressure to normal levels could prevent 51% of CHD events in men and 43% of CHD events in women, with control to optimal levels preventing 81% and 82% of CHD events, respectively.20Wong N.D. Pio J.R. Franklin S.S. L'Italien F.J. Kamath T.V. Williams G.R. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome.Am J Cardiol. 2003; 91: 1421-1426Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar The greater effect noted in that sample is likely a result of more poorly controlled risk factors among those with metabolic syndrome (but without DM) and/or because of worse risk factor control among this earlier cohort of subjects. There are several strengths and limitations to our study. Most importantly, NHANES provides for our sample being representative to the US adult population and, with sample weights, allows for us to calculate total estimated population impact in terms of number and proportion of CHD events that can be prevented among US adults with T2DM from risk factor control. In addition, NHANES has standardized measurement of risk factors; however, information such as on baseline CVD is based on self-report, thus there is some potential for misclassification of disease status resulting from this as we did not have results of invasive or noninvasive testing to confirm the absence of CVD in all included subjects. A strength of the UKPDS risk engine was that it was developed specifically in persons with T2DM and includes information on diabetes duration and HbA1c, which is not the case for more generalized CHD risk algorithms such as those from the Framingham Heart Study. But a potential limitation is that the UKPDS risk engine was based on persons with diabetes studied in the United Kingdom some 2 decades ago, which may not be representative of those with T2DM today in the United States, United Kingdom, or other countries where there are differences in population lifestyle, healthcare systems as well as use of newer and more effective treatments (e.g., statins, angiotensin converting enzyme inhibitors, and newer antidiabetic agents). Importantly, our assumptions regarding the impact of risk factor control on CHD event reduction assume that the effects of intervention would be equivalent to the prospective associations observed that are the basis of the UKPDS equations, and potential confounders in these relations are not addressed. Moreover, our estimates of preventable CHD events are based on projections for 10 years; longer-term risk algorithms would estimate greater CHD events preventable. In addition, our goals were based on those in use during the 2007 to 2012 period of the survey; evolving changes in goals may result in different numbers of preventable CHD events. UKPDS and NHANES also classify ethnic groups differently such that we could not determine who in NHANES were of Asian-Indian or other Asian ancestry and both these and those of Hispanic origin had to be classified as white in the UKPDS algorithm, and it is known that these ethnic groups may differ from whites in terms of their baseline CHD risk. However, a sensitivity analysis done on ethnicity did not materially change our results in terms of estimated proportion of CHD events preventable. Importantly, the UKPDS risk engine estimates for glucose lowering were based mainly on insulin and sulfonylurea data that have some level of cardiotoxicity compared with newer drugs more commonly used today, and hypoglycemia could also limit adherence; thus the benefit of A1c lowering on CHD risk could be underestimated. Also, because the UKPDS algorithm does not incorporate information on obesity, lifestyle, or other factors, such information, although available in our NHANES subjects, could not be incorporated in the UKPDS risk prediction algorithms, and therefore risk estimates and preventable events from risk factor control could have varied had these factors been included. Finally, given there are no guidelines for HDL-C as a therapeutic target in light of recent clinical trials, our overall estimates would obviously be impacted if our results involving "treatment" of HDL-C are not incorporated into our total risk factor modification projections. Our report suggests that over half of the CHD events (and more than 2/3 of projected CHD events in younger women and younger men) could be preventable from aggressive management of HbA1c, blood pressure, smoking, and lipids. This translates to preventing more than an estimated 600,000 CHD events in men and 400,000 CHD events in women in the United States over a 10-year period. Our study will hopefully motivate clinicians to stress multifactorial composite risk factor control in those with T2DM and has important implications for estimating the population-wide reduction in CHD events possible from attainment of standards in diabetes management. Dr. Nathan Wong is the guarantor who takes full responsibility for the work as a whole, including the study design, access to data, analysis of the data, and the decision to submit and publish the manuscript. Mr. Patao conducted the data analysis. Dr. Malik and Dr. Iloeje provided critical review and advice during the analysis phase and the preparation of the manuscript. Dr. Iloeje was an employee of Bristol Myers Squibb at the time of conduct of this study. Effect of Risk Factor Control on Simulated Coronary Heart Disease EventsAmerican Journal of CardiologyVol. 114Issue 4PreviewWong et al1 recently published a report using the UK Prospective Diabetes Study risk engine2 to estimate the 10-year probability of coronary heart disease (CHD) events for US adults with type 2 diabetes if they were treated under 3 different levels of risk factor control intensity (all to goal, nominal control, and aggressive control). The risk factors included smoking, glycated hemoglobin (HbA1c), systolic blood pressure (SBP), total cholesterol (TC), and high-density lipoprotein cholesterol. They found that the aggressive control scenario led to the largest number of preventable CHD events. Full-Text PDF
Referência(s)