ESC Congress 2016 - 23

Your FREE access to ESC Congress content all year long www.escardio.org/365 ESC CONGRESS 2016 IN REVIEW The primary outcome was MVEs (defined as a composite of the first occurrence of coronary heart disease [CHD] death, myocardial infarction [MI], stroke, or coronary revascularization). Secondary outcomes included major coronary events and CHD. The mean age was 60.7 years; 57% were women. Mean LDL-C was 3.4 mmol, the mean non-LDL-C was 4.0 mmol, and the mean SBP was 126.5 mm Hg (Table 1). A total of 14,368 MVEs occurred during up to 32 years of follow-up. Persons with LDL-C scores below the median had 12.1 mg/dL (.3 mmol) lower LDL-C and a corresponding 22% reduction in MVEs (ORMVE, 0.783; 95% CI, 0.755 to 0.812; P = 3.0x10-40). When adjusted for a standard decrement, each mmol reduction in LDL-C score was associated with a 54% lower risk of CV events. This is significantly greater than the reduction in the risk of CVD per mmol/L reduction in LDL-C observed in a meta-analysis of short-term statin trials (Pdiff = 8.0x10-19) [Cholesterol Treatment Trialists' Collaboration. Lancet. 2010]. Similarly, long-term exposure to 10 mm Hg lower SBP was associated with a 44.7% lower lifetime risk of CVD. Again, significantly greater than the 20% reduction in CVD risk per 10 mm Hg reduction in SBP observed in a meta-analysis of short-term blood pressure lowering trials (Pdiff = 1.6 x10-9) [Ettehad D et al. Lancet. 2016]. Persons with both LDL-C and SBP scores below the median had a 46% lower risk of MVE (Figure 2). Together, these data confirm that LDL-C and SBP both have causal and cumulative effects on the risk of CVD. The effect of long-term exposure to lower LDL-C, lower SBP or both was similar for all CV outcomes, and for all subgroups evaluated with no evidence for any significant heterogeneity of effect. The greater magnitude of reduction observed relative to those seen in trials of pharmacotherapy is most likely explained by the life-long exposure to differences in this cohort. Because their effects are multiplicative and cumulative over time, long-term exposure to a combination of even modestly lower LDL-C and SBP has the potential to dramatically reduce the lifetime risk of CVD, even among persons with apparently normal cholesterol and blood pressure. Table 1. Genetic Score Related Lipid and Blood Pressure Baseline Characteristics Reference Group LDL-C Score Below Median SBP Score Below Median LDL-C and SBP Score Below Median LDL-C, mg/dL (SD) 134.4 (31.8) 122.3 (33.1) 134.7 (32.7) 122.2 (32.3) Non-HDL-C, mg/dL (SD) 162.0 (36.8) 148.5 (35.1) 162.3 (37.7) 148.3 (36.3) SBP, mm Hg (SD) 128.1 (15.7) 128.3 (17.1) 125.1 (16.5) 125.0 (16.9) Characteristic Figure 2. Combined Effect of LDL-C and SBP on CV Events SBP Genetic Score LDL-C Effect Size SBP Effect Size ORMVE (95%CI) Botch LDL-C and SBP scores below median -12.2 mg/dL -3.1 mm Hg 0.542 (0.509-0.577) -12.1 LDL-C score below median mg/dL 0.2 mm Hg 0.758 (0.715-0.804) P(diff) = 1.4 x10-14 0.3 mg/dL -3.0 mm Hg 0.821 (0.779-0.865) P (diff)= 1.8 x10-23 SBP score below median 0.40 0.50 0.60 0.70 0.80 OR 0.90 0.0 P = 9.6 x10-83 1.10 LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure. Reproduced with permission from B Ference, MD, MPhil, MSc. Official Peer-Reviewed Highlights From ESC Congress 2016 23 http://www.escardio.org/365

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