ISHIB 2007 Innovating Vascular Health: Practical Applications to Clinical Practice Critical Challenges in Cardiovascular Disease Program Chairwoman Shawna D. Nesbitt, MD, MS Associate Professor Department of Internal Medicine Division of Hypertension University of Southwestern Texas Medical School Dallas, TX
Welcome and Program Overview CME-accredited symposium jointly sponsored by the American Society of Hypertension and CMEducation Resources, LLCCommercial Support: Sponsored by an independent educational grant from Novartis PharmaceuticalsMission statement: Improve patient care through evidence-based education, expert analysis, and case study-based managementProcesses: Strives for fair balance, clinical relevance, on-label indications for agents discussed, and emerging evidence and information from recent studiesCOI: Full faculty disclosures provided in syllabus and at the beginning of the program
Program Educational Objectives As a result of this session, physicians will be able to: • Identify the importance of early treatment of patients with high blood pressure, and the importance of treating both systolic and diastolic blood pressure abnormalities. • Implement clinical strategies that help patients achieve blood pressure goals as quickly as possible, using combination therapy, when indicated. • Identify prescribing strategies that reduce side effects and increase the likelihood of adherence to an antihypertensive drug regimen. • Characterize and distinguish among safety profiles of and efficacy characteristics of antihypertensive agents used in the African American population.
Program Educational Objectives • Recognize markers of target organ damage and learn which antihypertensive agents are useful for preventing end organ complications such as CV disease and diabetic renal disease. • Manage hypertension as a systematic disease, with multiple manifestations, and associations, including metabolic syndrome and associated risk factors. • Address complications linked to healthcare disparities observed in specific patient populations, and the importance of providing access, treatment, and monitoring of patients with multiple risk CV risk factors. • Manage African American patients with features of the metabolic syndrome, and its implications for multiple risk factor management
Program Faculty Program Chairwoman Shawna D. Nesbitt, MD, MS Associate Professor Department of Internal Medicine Division of Hypertension University of Southwestern Texas Medical School Dallas, Texas Ken Jamerson, MD Professor of Medicine Cardiovascular Medicine University of Michigan Health System Ann Arbor, Michigan Jackson T. Wright, Jr., MD, PhD, FACP Professor of Medicine Program Director, General Clinical Research Center Case Western Reserve University Director, Clinical Hypertension Program University Hospitals of Cleveland Chief, Case Western Reserve University Hypertension Section (Louis Stokes VAMC) Cleveland, Ohio
Faculty Disclosures Shawna D. Nesbitt, MD, MS Grant/Research Support: Pfizer Consultant: Novartis, BMS Speakers Bureau: Boerhinger Ingelheim, Novartis, AstraZeneca Ken Jamerson, MD Research Support: NIH, NHLBI, NIH, NIDDK, Novartis, King Pharmaceuticals Consultant: MSD, Pfizer, Novartis, Speedel Jackson T. Wright, Jr., MD, PhD, FACP Research Support: Glaxo Smith Kline, Novartis Consultant: Novartis, MSD, Sanofi, BMS, Pfizer, NIH Honoraria: Novartis, Biovail, Sanofi, Pfizer
Program Agenda 7:15 – 7:30 PM Introduction and Overview The Current Landscape of Cardiovascular Risk Management in African Americans— Where Co-morbidity Matters: The Evolving Relationship Between Risk Factors, Diabetes, Hypertension, and Vascular Complications Shawna D. Nesbitt, MD, MS 7:30 – 8:00 PM Are We in Control? An Epidemiological Examination of How Well We Are Managing Hypertension in Ethnic Minority Populations: The Importance of Early Risk Identification and Intervention—Getting to Goal and Staying There Ken Jamerson, MD
Program Agenda 8:00 – 8:25 PM Hypertension—A Systemic Disease Requiring Systematic Approaches to Therapy: Recent Clinical Practice Recommendations Focusing on Combination Therapy in Difficult-to-Treat Patient Populations with High Blood Pressure and Compelling Conditions Jackson T. Wright, Jr., MD, PhD, FACP 8:25 – 8:55 PM The Evolving Landscape of Antihypertensive Therapy: Direct Renin Inhibition, Combination Therapy, and Implications for African American and Other Ethnic Populations Shawna D. Nesbitt, MD, MS 8:55 PM Questions and Interactions with the Faculty
Introduction and Overview The Current Landscape of Cardiovascular Risk Management in African Americans—Where Co-morbidity MattersThe Evolving RelationshipBetween Risk Factors, Diabetes, Hypertension, And Vascular Complications Shawna D. Nesbitt MD, MS Associate Professor of Internal Medicine University of Texas Southwestern Dallas, Texas
The U.S. Population is Becoming Increasingly Diverse Changing Trends Hispanics are the fastest-growing segment of the population, and now account for 13% U.S., as do African Americans. The U.S. Asian population currently consists of 10.6 million people, and represents 4% U.S.,; however, this population group is expected to triple in size by 2050. Adapted from U.S. Census Bureau, 2004. Table 1a. Accessed Dec. 1, 2006.
Southern U.S. Has the Highest Concentration of African-Americans 25.0 to 60.0 12.3 to 24.9 5.0 to 12.2 0.3 to 4.9 People indicating exactly one race, Black or African American, as a percent of total population by state Adapted from U.S. Census Bureau, 2002 Redistricting Data (PL 94-171) Summary File
1.8% age adj. increase 7.2% age adj. increase M F Non-Hispanic Black Estimated Rates of US Adults With Hypertension by Sex, Race, and EthnicityNHANES 1988-1994 to 1999-2000 1988-1994 1999-2000 45 40 35 30 Hypertensive Adults(Rate, Percent ± SE) 25 20 15 10 5 0 M F M F Non-Hispanic White MexicanAmerican All Fields et al. Hypertension. 2004;44:398-404. Hajjar and Kotchen. JAMA. 2003;290:199–206
Hypertension Treatment and Control Rates by Race/Ethnicity: NHANES 2000 Percentage increase from 1988 to 2000 7.2 0.9 6.2 8.2 6.2 3.7 70 63 60.1 Treatment 55.6 60 Control 50 44.6 44 40.3 40 % 30 20 10 0 AfricanAmericans* Whites* MexicanAmericans *Non-Hispanic. Hajjar and Kotchen. JAMA. 2003;290:199–206.
Mortality From High Blood Pressure Higher in African Americans Overall Mortality Rates From Causes Related to Hypertension, 2003* 60 49.7 50 40.8 40 Mortality Rate, % 30 14.9 14.5 20 10 0 Male Female Male Female African American White In hypertensive African Americans, 30% and 20% of all deaths in men and women, respectively, may be due to high blood pressure. *High blood pressure listed as a primary or contributing cause of death. High blood pressure=systolic ≥140 mmHg or diastolic ≥90 mmHg, taking antihypertensive medicine, being told ≥2 times by a physician that you have high blood pressure. Adapted from Thom T et al. Circulation. 2006;113:e85–e151.
Patients Not at JNC VI BP Goals % Not at Goal BP Systolic DiastolicPatient Type (mm Hg) BP BP NHANES (1999-2000) Total hypertensives <140/90 57% 26% African American <140/90 60% 32% Mexican American/ Hispanic <140/90 63%30% Older patients (60 years) <140/90 71% 9% Symptomatic CHD <140/90 47% 4% Patients with diabetes† <130/85 81% 24% *Includes those 17 years of age with diagnosed and undiagnosed hypertension. National Center for Health Statistics. NHANES 1999-2000 (CD-ROM); †NHANES III.
70 60 50 40 30 20 10 0 0 1 ≥2 ≥3 White women African-American women White men African-American men Risk-Factor Clustering by Race and Sex Percentage Stone et al JAMA. 1996;275:1104-1112.
Obesity and Diabetes Among US Adults:Growing prevalence Obesity (BMI ≥30 kg/m2) Diagnosed diabetes +11.9% 30 +11.5% 8 6.5 6.6 6.6 6.4 24.3 5.9 25 6 23.9 23.7 23.0 Population (%) 21.8 20 4 15 2 0 0 2000 2001 2002 2003 2004* 2000 2001 2002 2003 2004* CDC. 2004 NHIS; www.cdc.gov/nchs/nhis.htm. *Jan–June
Age-Adjusted Prevalence of Diabetes* by Race/Ethnicity in the US American Indians/Alaska Natives Non-Hispanic Blacks 19% Hispanic/LatinoAmericans 15% Non-Hispanic Whites 14% 7% Percent *In people 20+ years old Sources: 1997-1999 National Health Interview Survey and 1988-1994 National Health and Nutrition Examination Survey (NHANES) estimates projected to year 2000. 1998 outpatient database of the Indian Health Service CDC. National Diabetes Fact Sheet. 2002.
Estimated Percentage of Americans Age 18 and Older Who Report No Leisure-Time Physical Activity by Race and Sex Source: Physical Activity and Health: A Report of the Surgeon General, United States Department of HHS
Diabetes: The Number One Cause of ESRD Other Glomerulonephritis No of Patients 10% 13% Projection Diabetes Hypertension 50.1% 27% The Rising Tide of ESRD 700 600 500 400 661,330 No. of ESRD Patients (x 1000) 300 372,407 200 326,217 100 R2 = 99.8% 0 1986 1984 1988 1990 1992 1998 1996 2004 1994 2000 2002 2010 2006 2008 Year USRDS. Annual data report. 2000.
Years of Potential Life Lost to Total Heart Disease Before Age 75 by Race and Gender 4000 3000 Years 2000 1000 0 1980 1980 1985 1985 1990 1990 1995 1995 White women African-American women White men African-American men Clark et al Heart Dis. 2001;3:97-108; National Vital Statistics System, Health, United States, 1996–97.
Failure to Reach Treatment GoalsCarries Costly Burden N = 1000 managed-care patients with treated hypertension Greater medication costs More physician visits 600 12 9.7 Mean drugcost perpatient per year* ($ US) 400 Mean visits per year 8 4.1 200 4 0 0 <130/85 ≥160/100 140/90 –159/99 <120 mm Hg ≥180 mm Hg 130/85 –139/89 Maximum SBP Controlled Uncontrolled Severity of hypertension (mm Hg) *Based on 1999 average wholesale price Paramore LC et al. Am J Manag Care. 2001;7:389-398.
Challenges and Solutions in Minority Populations Kenneth A. Jamerson, M.D.Professor of Cardiovascular Medicine University of MichiganMedical Director, Program for Multi-cultural HealthAnn Arbor, Michigan Are We in Control? The Importance of Early Risk Identification and Treatment Getting To Goal and Staying There in Ethnic Minority Populations
The Tecumseh Blood Pressure Study A prospective epidemiological study of the antecedents of hypertension and cardiovascular disease in 1,100 young men and women Ann Arbor Tecumseh
Tecumseh BP Study: Association of DBP and Other CHD Risk Factors Overweight Hematocrit Heart Rate Insulin DBP Cholesterol Triglycerides P<0.001 P<0.01 P<0.05 N=124 (aged 18-28 years) Adapted from Julius et al. JAMA 1990;264:354-358
Blood Pressure Trends in Tecumseh, Michigan * * * ** * * P< .01 * Hypertensive Normotensive S. Julius, et al: JAMA 264:354-358, 1990 P<.001 **
Causes and Causes for Concern Is There a Unique Etiology for Hypertension in African Americans?
Deciphering The Etiology and Associations The Association of Skin Color with Blood pressure in US blacks with Low Socioeconomic Status Klag, M J. Whelton, P K. Coresh, J. Grim, C E. Kuller, L H. JAMA. 1991 Feb 6;265(5):639-40; Abstract To determine the association of skin color, measured by a reflectometer, with blood pressure in US blacks, we studied a community sample of 457 blacks from three US cities. Persons taking antihypertensive medications were excluded. Both systolic and diastolic blood pressure were higher in darker persons and increased by 2 mm Hg for every 1-SD increase in skin darkness. However, the association was dependent on socioeconomic status, whether measured by education or an index consisting of education, occupation, and ethnicity, being present only in person with lower levels of either indicator. Using multiple linear regression, both systolic and diastolic blood pressure remained significantly associated with darker skin color in the lower levels of socioeconomic status, independent of age, body mass index, and concentrations of blood glucose, serum urea nitrogen, serum uric acid, and urinary sodium and potassium. The association of skin color with blood pressure only in low socioeconomic strata may be due to the lesser ability of such groups to deal with the psychosocial stress associated with darker skin color. However, these findings also are consistent with an interaction between an environmental factor associated with low socioeconomic status and a susceptible gene that has a higher prevalence in persons with darker skin color.
Response to Therapy A Critical Issue for Drug Selection and Care Do African Americans respond to antihypertensive therapy differently than other races or ethnic groups?
Blood Pressure Response to Quinapril: The ATIME Study 20.0 Mean –15.3 SD 12.2 Lower Quartile –7.3 Upper Quartile –23.5 Interquartile Range 16.2 15.0 White, % 10.0 5.0 0 20.0 Mean –10.5 SD 13.4 Lower Quartile –2.2 Upper Quartile –20.0 Interquartile Range 17.8 15.0 African American, % 10.0 5.0 0 39 27 15 3 –9 –21 –33 –45 –57 SBP (average change) SD = standard deviation. Mokwe E et al. Hypertension. 2004;43(6):1202–7.
Is It Important To Block The RAS In African Americans? Landmark Trials That Give Us Data, Guidance, and Perspective • HOPE • PROGRESS • SOLVD • ValHeft • V-Heft • LIFE • OCTAVE • ALLHAT
Landmark and Longitudinal Studies African American Study of Kidney Disease and Hypertension
Cumulative Incidence of Confirmed Declining GFR Event,Dialysis or Death by Drug Group(Data as of 10/19/01) p-value A vs B C vs B* A vs C* adjusted .042 .19 .005 Cumulative Incidence .
Implications Of The AASK Study • Aggressive control of blood pressure can eliminate ethnic differences in ESRD • Inadequate treatment of hypertension may cause excess risk of target organ disease • Cultural, rather than genetic differences, may underlay the excess risk of hypertensive ESRD
International Society of Hypertension in Blacks IMPACT Campaign Science Guidelines Behavioral Change
Vascular Matrix Summit • Dr. Gary Gibbons • Dr. Abraham Aviv • Rick Kittles, MD • Charles Rotimi, MD • David Harrison, MD • Willa Hsueh, MD • Helmy Siragy, MD • Douglas Vaughan, MD • Dr. Brent Egan • Ken Jamerson, MD
Models to Explain Health Disparities • Racial Genetic Model Cause of HD: Population differences in the distribution of genetic variants • Health-behavior Model Cause of HD: Differences between R/E groups in the distribution of individual behaviors related to health such as diet, exercise, and tobacco use • SES Model Cause of HD: Over-representation of some R/E groups within lower SES • Psychosocial Stress Model Cause of HD: Stresses associated with minority group status, especially the experience of racism and discrimination
Critical Relationships Race (Social) Disease Ancestry (Genetic)
Ancestry Informative Markers (AIMs) Although much genetic variation (85-90%) is shared among all human populations, about 5% of SNPs have high levels of allele frequency differential (d>50%). We call these markers Ancestry Informative Markers (AIMs).
Ancestry Can Be Estimated Across Chromosomal Regions Smith et al. AJHG 74:1001-1013, 2004 Seldin et al. Genome Res. 14:1076 -1084, 2004
European Genetic Contribution in African-American Populations Living in Different Areas of the U.S. Parra et al. AJHG 1998; Parra et al. AJPA 2002; Kittles et al. unpublished
Era of Genomic Ancestry and Challenges Related to Health • Group definition and membership. • Can we accurately assess genomic ancestry? • How does genomic ancestry relate to skin color and possibly SES? • How useful is genomic ancestry for informing us about disease risk? • Health Disparities: are they due to biological differences? • How do we prevent repeating the negative past abuses of “race”.
Accomplishing Something RESULTS BP Control at 18 Months
ACCOMPLISH: Hypothesis • ACCOMPLISH will test a new strategy for the treatment of hypertension: Dual therapy provided in a single tablet. • The combination of benazepril and amlodipine will reduce cardiovascular morbidity and mortality in patients with high-risk hypertension by 15% when compared to the combination of benazepril and HCTZ. Jamerson KA et al. Am J Hypertens. 2004;17:793–801.
ACCOMPLISH: Primary Endpoint Time to first event of composite cardiovascular morbidity and mortality CV MORBIDITY • Nonfatal MI • Nonfatal stroke • Hospitalization for unstable angina • Resuscitated sudden cardiac death • Coronary revascularization procedures CV MORTALITY • Sudden cardiac death • Fatal MI • Fatal stroke • Death due to coronary intervention, congestive heart failure, or other cardiovascular causes Jamerson KA et al. Am J Hypertens. 2004;17:793–801.
ACCOMPLISH: Statistical Power • 1,642 primary endpoints needed (~5 years) • 90% power to detect a 15% risk reduction for the primary endpoint at a two-sided overall significance level of 5% • Four (4) interim analyses and 1 final analysis • Allow for lost-to-follow-up rate of less than 5% Jamerson KA et al. Am J Hypertens. 2004;17:793–801.