ARIC Manuscript Proposal # 947. PC Reviewed: 07/01/03 Status: A Priority: 2 SC Reviewed: 07/18/03 Status: A Priority: 2

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ARIC Manuscript Proposal # 947 PC Reviewed: 07/01/03 Status: A Priority: 2 SC Reviewed: 07/18/03 Status: A Priority: 2 1.a. Full Title: The Impact of Treatment and Adequate Control of Blood Pressure for Hypertension on Left Ventricular Hypertrophy b. Abbreviated Title (Length 26 characters): LVH & Hypertension BP Control 2. Writing Group (list individual with lead responsibility first): Lead: Address: Hui Han Jackson Heart Study Jackson Medical Mall 350 Woodrow Wilson Drive Jackson MS 39213 Phone: Fax: E-mail: Writing group members: Herman Taylor Jr, Dan Jones, Jun Pan, Bob Garrison Timeline: Complete analysis Fall, 2003 Submit first draft to publications committee Spring, 2004 Submit to Journal Summer, 2004 3. Rationale: Hypertension is a major risk factor for the development of congestive heart failure and coronary heart diseases. As Americans age, more and more people become hypertensive. According to NHANES III survey, hypertension affects about 50 million Americans and approximately 1 billion worldwide. The treatment of hypertension is the most common reason in the United Stated for office visits to physicians and for use of prescription drugs. Despite the importance of hypertension in the practice of medicine and advances in antihypertensive therapy, control of hypertension is far from adequate. Recent data from 1999-2000 indicates that only 59% of hypertensives were treated. Among those treated, only 34% reached the goal levels of <140/90 mm Hg, far below the goal of 50% proposed by Health People 2010 project. Numerous findings have demonstrated that hypertensive patients develop a wide spectrum of cardiac structural changes such as left ventricular hypertrophy (either concentric or eccentric), isolated septal thickness, or increased left ventricular mass. These conditions are more apparent especially for hypertensive patients who either do not seek medication, or who take antihypertensive medications but fail to control their blood

pressure successfully. The data from echocardiographic component of ARIC study on the African Americans in Jackson site provides excellent resource in elucidating the left ventricular structural change to the success of blood pressure control. In addition, the recently announced JNC VII guidelines recommend that individuals with BP 120-139/80-29 mmhg should be considered as prehypertensives and require healthpromoting lifestyle modifications to prevent CVD. This data can provide information to accommodate the new guidelines in terms of echocardiographically evaluated left ventricular structure. 5. Main Hypothesis/Study Questions: Our main interest is to evaluate the prevalence of left ventricular hypertrophy for different groups of individuals based on their hypertension status and blood pressure control level. Four groups will be generated, which are: 1)Non-hypertensive group, 2)Untreated hypertensive group, 3) Group of treated hypertensives with adequate blood pressure control, 4)Group of treated hypertensives with inadequate blood pressure control. The following hypothesis will be investigated: 1) For hypertensive patients, is the prevalence of LVH impacted by successful blood pressure control? 2) For untreated hypertensive group and group of treated hypertensives with poorlycontrolled blood pressure, are their LV structures different from the group of hypertension patients with adequate blood pressure control? 3) Within the Non-hypertensive group, do the prehypertensive people (120-139/80-29 mmhg) have elevated left ventricular mass compared to normotensive people (<120/80 mmhg)? For a second analysis, we would like to compare the differential control of different components of blood pressure. Only hypertensive patients will be used for this purpose, who will be grouped by different control of SBP, DBP, or both. The following hypothesis will be investigated: 1) What is LVH and LV mass more closely related, control of SBP or control of DBP? 2) What are the LVH patterns for the hypertensive patients who did not reach their SBP goal? 3) What are the LVH patterns for the hypertensive patients who did not reach their DBP goal? 6. Data (variables, time window, source, inclusions/exclusions): Study population: Only people who have valid blood pressure data on both baseline and subsequent clinical visits (visit 2 and visit 3) and people who have undergone the echocardiographic exam will be included in this study. There are approximately 2400 participants for this study, who are all African Americans of the Jackson site of the ARIC cohort.

Echocardiographic variables: Echo M-mode derived measurements including LV mass, left ventricular hypertrophy, patterns of left ventricular hypertrophy (concentric LVH, eccentric LVH, LV remodeling), left ventricular geometry. Analysis Plan and the Blood Pressure Control Classification: Office blood pressure measurements and information of taking anti-hypertensive agents are available in visit 1, visit 2 and visit 3 (the time of echocardiogram measurement). For the purpose of first analysis, the population will be divided into four groups. The Non-hypertensive group includes those SBP < 140 mmhg and DBP < 90 mmhg at baseline and remain so in subsequent clinic visits. People who are hypertensive (SBP>140 mmhg or DBP >90 mmhg) at baseline will be further divided into three groups based on whether they take anti-hypertensive medication and whether their blood pressure level at subsequent visits reach goal level of <140/90 mmhg, or <130/80 for patients with diabetes or chronic kidney disease. These three groups will be called Untreated Hypertensive group, Treated HT with Adequate BP Control group, and Treated HT without Adequate BP Control group. Contrasts of LVH, LV geometry among these groups will be made. The incident hypertension (people who develop HTN after baseline visit) will not be included in this analysis due to short follow up period. Only hypertensive patients will be used for the purpose of second analysis. Success of hypertension control to the goal of SBP, to the goal of DBP, or both will be investigated. Success in SBP control is defined as SBP < 130 mmhg for concomitant diabetes/chronic kidney disease patients, and <140 mmhg otherwise. Success in DBP control is defined as DBP < 80 mmhg for concomitant diabetes/chronic kidney disease patients, and <90 mmhg otherwise. Success in overall control is defined as joint control of SBP and DBP. The rate of LVH in adequately controlled vs inadequately controlled will be compared. Key covariates to be adjusted for: Age, gender, race, diabetics, body mass index, serum LDL, serum HDL, serum total cholesterol, anemia, etc. Exclusion criteria: Missing data on blood pressure measurements, missing relevant data on echocardiograph measurements. 7.a. Will the data be used for non-cvd analysis in this manuscript? Yes _x_ No b. If Yes, is the author aware that the file ICTDER02 must be used to exclude persons with a value RES_OTH = CVD Research for non-dna analysis, and for DNA analysis RES_DNA = CVD Research would be used? Yes No (This file ICTDER02 has been distributed to ARIC PIs, and contains the responses to consent updates related to stored sample use for research.) 8.a. Will the DNA data be used in this manuscript? Yes x_ No 8.b. If yes, is the author aware that either DNA data distributed by the Coordinating Center must be used, or the file ICTDER02 must be used to exclude those with value RES_DNA = No use/storage DNA? Yes No 9. The lead author of this manuscript proposal has reviewed the list of existing ARIC Study manuscript proposals and has found no overlap between this proposal and previously approved manuscript proposals either published or still in active status.

ARIC Investigators have access to the publications lists under the Study Members Area of the web site at: http://bios.unc.edu/units/cscc/aric/stdy/studymem.html x Yes No 10. What are the most related manuscript proposals in ARIC (authors are encouraged to contact lead authors of these proposals for comments on the new proposal or collaboration)? There are no directly overlapped proposals. Here are the most related proposals: MS 146. Neito et al. Population Awareness and Control of Hypertension and Hypercholesterolemia. Arch Intern Med 1995; 155:677-684. MS 674 Ervin Fox et al. Independent and combined influences of body mass index and blood pressure on left ventricular mass index and geometry in African Americans. MS 452 Arnett DK et al. The longitudinal relationship between diastolic and isolated systolic hypertension. 11. Manuscript preparation is expected to be completed in one to three years. If a manuscript is not submitted for ARIC review at the end of the 3-years from the date of the approval, the manuscript proposal will expire. REFERENCES 1. Mancia G, Carugo S, Grassi G, Lanzarotti A, Schiavina R, Cesana G, Sega R. Prevalence of left ventricular hypertrophy in hypertensive patients without and with blood pressure control: data from the PAMELA population. Pressioni Arteriose Monitorate E Loro Associazioni. Hypertension. 2002 Mar 1;39(3):744-9. 2. Chobanian AV, Bakris GL, Black HR, Cshman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. JAMA 2003 May21, 289(19): 2560-2572. 3. Lloyd-Jones DM, Evans JC, Larson MG, O'Donnell CJ, Roccella EJ, Levy D. Differential control of systolic and diastolic blood pressure : factors associated with lack of blood pressure control in the community. Hypertension 2000 Oct;36(4):594-9 4. Sega R, Corrao G, Bombelli M, Beltrame L, Facchetti R, Grassi G, Ferrario M, Mancia G. Blood pressure variability and organ damage in a general population: results from the PAMELA study (Pressioni Arteriose Monitorate E Loro Associazioni). Hypertension. 2002 Feb;39 (2 Pt 2):710-4. 5. Parati G, Mancia G. Blood pressure variability as a risk factor. Blood Press Monit. 2001 Dec;6(6):341-7. 6. Mancia G, Parati G, Hennig M, Flatau B, Omboni S, Glavina F, Costa B, Scherz R, Bond G, Zanchetti A; Relation between blood pressure variability and carotid artery damage in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis (ELSA). J Hypertens. 2001 Nov;19(11):1981-9. 7. Rywik SL, Davis CE, Pajak A, Broda G, Folsom AR, Kawalec E, Williams OD; Poland and U.S. collaborative study on cardiovascular epidemiology hypertension in the community: prevalence, awareness, treatment, and control of hypertension in the Pol-

MONICA Project and the U.S. Atherosclerosis Risk in Communities Study. Ann Epidemiol. 1998 Jan;8(1):3-13. 8. Liao D, Arnett DK, Tyroler HA, Riley WA, Chambless LE, Szklo M, Heiss G. Arterial stiffness and the development of hypertension. The ARIC study. Hypertension. 1999 Aug;34(2):201-6. 9. Arnett DK, Rautaharju P, Crow R, Folsom AR, Ekelund LG, Hutchinson R, Tyroler HA, Heiss G. Black-white differences in electrocardiographic left ventricular mass and its association with blood pressure (the ARIC study). Atherosclerosis Risk in Communities. Am J Cardiol. 1994 Aug 1;74(3):247-52. 10. Mancia G, Bombelli M, Lanzarotti A, Grassi G, Cesana G, Zanchetti A, Sega R. Systolic vs diastolic blood pressure control in the hypertensive patients of the PAMELA population. Pressioni Arteriose Monitorate E Loro Associazioni. Arch Intern Med. 2002 Mar 11;162(5):582-6. 11. Cuspidi C, Lonati L, Sampieri L, Macca G, Michev I, Salerno M, Fusi V, Leonetti G, Zanchetti A. Impact of blood pressure control on prevalence of left ventricular hypertrophy in treated hypertensive patients. Cardiology. 2000;93(3):149-54. 12. Grandi AM, Broggi R, Colombo S, Santillo R, Imperiale D, Bertolini A, Guasti L, Venco A. Left ventricular changes in isolated office hypertension: a blood pressure-matched comparison with normotension and sustained hypertension. Arch Intern Med. 2001 Dec 10-24;161(22):2677-81. 13. Missault LH, De Buyzere ML, De Bacquer DD, Duprez DD, Clement DL. Relationship between left ventricular mass and blood pressure in treated hypertension. J Hum Hypertens. 2002 Jan;16(1):61-6. 14. Cuspidi C, Lonati L, Sampieri L, Michev I, Macca G, Rocanova JI, Salerno M, Fusi V, Leonetti G, Zanchetti A. Prevalence of target organ damage in treated hypertensive patients: different impact of clinic and ambulatory blood pressure control. J Hypertens. 2000 Jun;18(6):803-9. 15. Mancia G, Sega R, Milesi C, Cesana G, Zanchetti A. Blood-pressure control in the hypertensive population. Lancet. 1997 Feb 15;349(9050):454-7. 16. Mancia G, Giannattasio C, Turrini D, Grassi G, Omboni S. Structural cardiovascular alterations and blood pressure variability in human hypertension. J Hypertens Suppl. 1995 Aug;13(2):S7-14. 17. Mayet J, Chapman N, Li CK, Shahi M, Poulter NR, Sever PS, Foale RA, Thom SA. Ethnic differences in the hypertensive heart and 24-hour blood pressure profile. Hypertension. 1998 May;31(5):1190-4.