Independent Contribution of A1C, Systolic Blood Pressure, and LDL Cholesterol Control to Risk of Cardiovascular Disease Hospitalizations in Type 2 Diabetes: An Observational Cohort Study
Cardiovascular disease (CVD) prevention in diabetes requires broad-based treatment of dyslipidemia, hypertension, and hyperglycemia. The independent contribution of all combinations of risk factor control to CVD risk has not been evaluated.
To estimate the independent association of control of glycosylated hemoglobin (A1C), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with risk of cardiovascular disease hospitalization.
Non-concurrent longitudinal cohort study.
The study included 26,636 patients with type 2 diabetes who were members of an integrated group model HMO with multiple A1C, SBP, and LDL-C measurements.
Patients were followed for a mean (SD) of 5.6 (2.5) years until they died or disenrolled, or until 31 December 2010. The outcome was a first-observed CVD hospitalization. Using the mean of all A1C, SBP, and LDL-C measures during follow-up, we created dichotomous categories of A1C control (< 7 %), SBP control (< 130 mmHg), and LDL-C control (< 100 mg/dL) to estimate the incidence rate of CVD hospitalization associated with all combinations of risk factor control adjusting for demographic and clinical characteristics.
Patients with no controlled risk factors (18.2/1,000 person-years, 95 % CI 16.5−20.2) or with only A1C in control (16.9, 15.0−19.0) had the highest rate of CVD hospitalization, whereas those with all three risk factors controlled (7.2, 6.2−8.4) or with SBP and LDL-C in control (6.1, 5.1−7.2) had the lowest rates. Those with only SBP or LDL-C in control, A1C and SBP controlled, or A1C and LDL-C controlled had statistically similar incidence between the highest and lowest rates.
Maintaining SBP < 130 mmHg or LDL-C < 100 mg/dL was significantly associated with reduced CVD hospitalization risk, especially when both risk factors were well controlled. Maintaining A1C < 7 % was not independently associated with reduced CVD hospitalization risk.
- Standards of medical care in diabetes–2012. Diabetes Care 35: pp. S11-S63
- Gerstein, HC, Miller, ME, Byington, RP, Goff, DC, Bigger, JT, Buse, JB (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358: pp. 2545-2559 CrossRef
- Patel, A, MacMahon, S, Chalmers, J, Neal, B, Billot, L, Woodward, M (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358: pp. 2560-2572 CrossRef
- Duckworth, W, Abraira, C, Moritz, T, Reda, D, Emanuele, N, Reaven, PD (2009) Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 360: pp. 129-139 CrossRef
- Stratton, IM, Alder, AI, Neil, HAW, Matthews, DR, Manley, SE, Cull, CA (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321: pp. 405-412 CrossRef
- Colayco, DC, Niu, F, McCombs, JS, Cheetham, TC (2011) A1C and cardiovascular outcomes in type 2 diabetes: a nested case–control study. Diabetes Care 34: pp. 77-83 CrossRef
- Selvin, E, Steffes, MW, Zhu, H, Matsushita, K, Wagenknecht, L, Pankow, J (2010) Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 362: pp. 800-811 CrossRef
- Grundy, SM, Cleeman, JI, Bairey-Merz, CN, Brewer, HB, Clark, LT, Hunninghake, DB (2004) Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110: pp. 227-239 CrossRef
- National High Blood Pressure Education Working Group report on hypertension in diabetes. Hypertension 23: pp. 145-158 CrossRef
- Gaede, P, Vedel, P, Larsen, N, Jensen, GV, Parving, HH, Pedersen, O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348: pp. 383-393 CrossRef
- Buse, JB, Ginsberg, HN, Bakris, GL, Clark, NG, Costa, F, Eckel, R (2007) Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 30: pp. 162-172 CrossRef
- Skyler, JS, Bergenstal, R, Bonow, RO, Buse, J, Deedwania, P, Gale, EAM (2009) Intensive glycemic control and the prevention of cardiovascular events: Implications of the ACCORD, ADVANCE, and VA Diabetes trials. Diabetes Care 32: pp. 187-192 CrossRef
- Stratton, IM, Matthews, DR (2006) Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia 49: pp. 1761-1769 CrossRef
- Gudbjornsdotir, S, Eliasson, B, Eeg-Olofsson, K, Zethelius, B, Cederholm, J (2011) on behalf of the National Diabetes Register (NDR). Additive effoects of glycaemia and dyslipidemia on risk of cardiovascular disease in type 2 diabetes: an observational study from the Swedish National Diabetes Register. Diabetologia 54: pp. 2544-2551 CrossRef
- Levey, AS, Bosch, JP, Lewis, JB, Greene, T, Rogers, N, Roth, D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 130: pp. 461-470 CrossRef
- Zoungas, S, Galan, BE, Ninomiya, T, Grobbee, D, Hamet, P, Heller, S (2009) Combined effects of routine blood pressure lowering and intensive glucose control on macrovascular and microvascular outcomes in patients with type 2 diabetes: New results from the ADVANCE trial. Diabetes Care 32: pp. 2068-2074 CrossRef
- Cederholm, J, Zethelius, B, Nilsson, PM, Eeg-Olofsson, K, Eliasson, B, Gudbjornsdottir, S (2009) Effect of tight control of HbA1c and blood pressure on cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR). Diab Res Clin Pract 86: pp. 74-81 CrossRef
- Gaede, P, Lund-Anderson, H, Parving, HH, Pederson, O (2008) Effect of a multi-factorial intervention on mortality in type 2 diabetes. N Engl J Med 358: pp. 580-591 CrossRef
- Inzucchi, SE, Bergenstal, RM, Buse, JB, Diamant, M, Ferrannini, E, Nauck, M (2012) Management of Hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care 35: pp. 1364-1379 CrossRef
- UKPDS 33: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes. Lancet 352: pp. 837-851 CrossRef
- Ismail-Beigi, F, Craven, T, Banerji, MA, Basile, J, Calles, J, Cohen, RM (2010) Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 376: pp. 419-430 CrossRef
- Eeg-Olofsson, K, Cederholm, J, Nilsson, PM, Zethelius, B, Svensson, AM, Gudbjornsdotir, S (2010) New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study for the Swedish National Diabetes Register (NDR). J Intern Med 268: pp. 471-482 CrossRef
- Elley, CR, Kenealy, T, Robinson, E, Drury, PL (2008) Glycated haemoglobin and cardiovascular outcomes in people with type 2 diabetes: a large prospective cohort study. Diabet Med 25: pp. 1295-1301
- Currie, CJ, Peters, JR, Tynan, A, Evans, M, Heine, RJ, Bracco, OL (2010) Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet 375: pp. 481-489 CrossRef
- Zoungas, S, Chalmers, J, Ninomiya, T, Li, Q, Cooper, ME, Colagiuri, S (2012) Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds. Diabetologia 55: pp. 636-643 CrossRef
- Jorgensen, CH, Gislason, GH, Bretler, D, Sorensen, R, Norgaard, ML, Hansen, ML (2011) Glyburide increases risk in patients with diabetes mellitus after emergent percutaneous intervention for myocardial infarction—A nationwide study. Int J Cardiol 152: pp. 327-331 CrossRef
- Selvin, E, Bolen, S, Yeh, HC, Wiley, C, Wilson, LM, Marinopoulos, SS (2008) Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med 168: pp. 2070-2080 CrossRef
- Aronow, WS, Fleg, JL, Pepine, CJ, Artinian, NT, Bakris, G, Brown, AS (2011) ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 57: pp. 2037-114 CrossRef
- Cushman, WC, Evans, GW, Byington, RP, Goff, DC, Grimm, RH, Cutler, JA (2010) Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 362: pp. 1575-1585 CrossRef
- Cooper-DeHoff, RM, Gong, Y, Handberg, EM, Bavry, AA, Denardo, SJ, Bakris, GL (2010) Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA 304: pp. 61-68 CrossRef
- Redon, J, Mancia, G, Sleight, P, Schumacher, H, Gao, P, Pogue, J (2012) Safety and efficacy of low blood pressures among patients with diabetes: subgroup analyses from the ONTARGET (ONgoing telmisartan alone and in combination with ramipril global endpoint trial). J Am Coll Cardiol 59: pp. 74-83 CrossRef
- Schramm, TK, Gislason, GH, Kober, L, Rasmussen, S, Rasmussen, JN, Abildstrom, SZ (2008) Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people. Circulation 117: pp. 1945-1954 CrossRef
- Brunzell, JD, Davidson, M, Furberg, CD, Goldberg, RB, Howard, BV, Stein, JH (2008) Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol 51: pp. 1512-1524 CrossRef
- Independent Contribution of A1C, Systolic Blood Pressure, and LDL Cholesterol Control to Risk of Cardiovascular Disease Hospitalizations in Type 2 Diabetes: An Observational Cohort Study
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Journal of General Internal Medicine
Volume 28, Issue 5 , pp 691-697
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- glycemic control
- blood pressure control
- cholesterol control
- CVD risk factors
- Industry Sectors
- Author Affiliations
- 1. Kaiser Permanente Center for Health Research, Portland, OR, USA
- 4. Center for Health Research, 3800 N. Interstate Avenue, Portland, OR, 97227-1098, USA
- 2. Formerly AstraZeneca LP, Wilmington, DE, USA
- 3. AstraZeneca LP, Wilmington, DE, USA