Macrovascular Residual Risk What risk remains after LDL-C management and intensive therapy?
Defining Residual Vascular Risk The risk of macrovascular events and microvascular complications which persists in most patients despite current standards of achievement of low-density lipoprotein (LDL-C) goal and intensive control of blood pressure and blood glucose Fruchart JC, et al. Am J Cardiol 2008;102:: 1K-34K.
Despite Treatment Residual Cardiovascular Risk Remains in Hypertensive Patients Meta-analysis of 29 RCTs conducted in 162,341 patients Decrease in total major cardiovascular (CV) events (stroke," CHD, heart failure, CV death) compares with placebo: ACE inhibitors 22% Calcium antagonists: 18% Angiotensin receptor blockers: 10% No differences in total major CV events between the different treatment regimens." About 80% of major CV events are not prevented by BP lowering treatment Turnbull F. Lancet 2003;362:1527-35.
Despite Achievement of LDL-C goals, Patients are Still at High Risk of Major Macrovascular Events" Lowering LDL-C by 1 mmol/l (40 mg/dl) with statins reduces major coronary events by 23%, but an unaddressed CV residual risk of 77% remains Statin better Control better RR (95% CI) P- Value All-cause mortality CHD mortality Nonfatal MI Any major coronary event Coronary revascularisation Stroke 0.88 (0.84-0.91) 0.81 (0.76-0.85) 0.74 (0.70-0.80) 0.77 (0.74-0.80) 0.76 (0.73-0.80) 0.83 (0.78-0.88) 0 0,5 1,0 1,5 Baigent C, et al. Lancet 2005;366:1267-78
Statin Therapy is Not Sufficient Especially in Diabetics Patients Significant reductions in both diabetics and non-diabetics Significant reductions in non-diabetics only Incidence of event and prior diabetes Reduction per mmol/l LDL-C reduction Incidence of mortality and prior diabetes Reduction per mmol/l LDL-C reduction Major vascular events Diabetes No diabetes 21% 21% All-cause mortality Diabetes No diabetes 9% 13% Major coronary events Diabetes No diabetes 22% 23% CHD mortality Diabetes No diabetes 12% 22% Stroke Diabetes No diabetes 21% 16% There is a noticeable residual risk of fatal and non-fatal vascular events in diabetics treated with statins for about 5 years Kearney PM, et al. Lancet 2008;371:117-25
Elevated Residual Risk of CV Events Associated with Low HDL-C and High TG levels even when LDL-C <70 mg/dl (<1.8 mmol/l) HDL-C TNT study 5-yr risk of major cardiovascular events (%) 10 9 8 7 6 5 4 3 2 1 0 Q1 (<38) (<1.0) Q2 (38<42) (1.0<1.1) Q3 (42<47) (1.2<1.3) Q4 (47<55) (1.2<1.3) Q5 ( 55) (>1.3) -39% p=0.03 No. of Events No. of Patients Quintile of HDL-C Level mg/dl (mmol/l) 57 473 50 525 34 550 34 569 35 544 Barter P et al. N Engl J Med. 2007; 357:1301-10.
Elevated Residual Risk of CV Events Associated with Low HDL-C and High TG levels even when LDL-C <70 mg/dl (<1.8 mmol/l) TG PROVE IT-TIMI 22 study 30-day risk of death, MI or recurrent ACS (%) 25 20 15 10 5 0 20.3 200 (2.2) (n=603) 13.5 <200 (2.2) (n=2,796) +50% p=0.001 On-treatment TG mg/dl (mmol/l) in patients who achieved LDL-C <70 mg/dl on statin therapy Miller M et al. J Am Coll Cardiol. 200851:724-30.
ACCORD Diabetic Patients with Elevated TG - Low HDL-C Patients with Atherogenic Dyslipidaemia (HDL <34 and TG>204 mg/dl*) had a 70% higher relative risk of major CV events** compared to those without Atherogenic Dyslipidemia, despite achieving a mean LDL-C of 80 mg/dl 20 15 +70% 17.32 Simvastatin 10 10.11 5 0 Without Atherogenic Dyslipidemia With Atherogenic Dyslipidemia * HDL<0.88 mmol/l; TG <2.3 mmol/l **Major CV events defined as CV death, nonfatal MI and nonfatal stroke ACCORD Study Group. N Engl J Med March 14, 2010. Epub.
Intensive Glycemic Control Does Not Seem to Further Reduce CVD Events in Patients with T2D ACCORD glycemic arm results 1 10,251 patients with T2D were randomized to Intensive glycemic control (target HbA1c <6%) Standard glycemic control (target 7 HbA1c 7.9%) Primary endpoint: major CV event Results Intensive glycemic control increased mortality by 22% (P=0.04) after a mean of 3.5 years follow-up 1. Gerstein HC, et al. N Engl J Med 2008;358:2545-59. 2. Ninomiya JK, et al. Circulation 2004;109:42-6.
Residual Vascular Risk is Particularly Important in " Diabetes Management Leading cause of blindness in adults 24,000 new cases Each year in US Leading cause of end-stage renal Disease in adults 44% new cases/yr Leading cause of non traumatic limb amputation 60% new cases/yr Diabetic retinopathy Diabetic nephropathy Diabetic neuropathy Stroke Cardiovascular disease 2 to 4-fold increase In cerebrovascular disease and stroke 8 out of 10 diabetic patients die from cardiovascular events 5-10 years reduction in life expectancy NIDKK, National Diabetes Statistics facts sheet. HHS, NIH, 2006