OBJECTIVES: The purpose of this study was to estimate the effect of long-term exposure to lower plasma low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD). BACKGROUND: LDL-C is causally related to the risk of CHD. However, the association between long-term exposure to lower LDL-C beginning early in life and the risk of CHD has not been reliably quantified. METHODS: We conducted a series of meta-analyses to estimate the effect of long-term exposure to lower LDL-C on the risk of CHD mediated by 9 polymorphisms in 6 different genes. We then combined these Mendelian randomization studies in a meta-analysis to obtain a more precise estimate of the effect of long-term exposure to lower LDL-C and compared it with the clinical benefit associated with the same magnitude of LDL-C reduction during treatment with a statin. RESULTS: All 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I(2) = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10(-19)). CONCLUSIONS: Prolonged exposure to lower LDL-C beginning early in life is associated with a substantially greater reduction in the risk of CHD than the current practice of lowering LDL-C beginning later in life.
OBJECTIVES: The purpose of this study was to estimate the effect of long-term exposure to lower plasma low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD). BACKGROUND:LDL-C is causally related to the risk of CHD. However, the association between long-term exposure to lower LDL-C beginning early in life and the risk of CHD has not been reliably quantified. METHODS: We conducted a series of meta-analyses to estimate the effect of long-term exposure to lower LDL-C on the risk of CHD mediated by 9 polymorphisms in 6 different genes. We then combined these Mendelian randomization studies in a meta-analysis to obtain a more precise estimate of the effect of long-term exposure to lower LDL-C and compared it with the clinical benefit associated with the same magnitude of LDL-C reduction during treatment with a statin. RESULTS: All 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I(2) = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10(-19)). CONCLUSIONS: Prolonged exposure to lower LDL-C beginning early in life is associated with a substantially greater reduction in the risk of CHD than the current practice of lowering LDL-C beginning later in life.
Authors: Michael M Mendelson; Asya Lyass; Christopher J O'Donnell; Ralph B D'Agostino; Daniel Levy Journal: JAMA Cardiol Date: 2016-04-01 Impact factor: 14.676
Authors: G Klose; F U Beil; H Dieplinger; A von Eckardstein; B Föger; I Gouni-Berthold; W Koenig; G M Kostner; U Landmesser; U Laufs; F Leistikow; W März; M Merkel; D Müller-Wieland; G Noll; K G Parhofer; B Paulweber; W Riesen; J R Schaefer; E Steinhagen-Thiessen; A Steinmetz; H Toplak; C Wanner; E Windler Journal: Internist (Berl) Date: 2014-05 Impact factor: 0.743
Authors: Nina R Joyce; Gregory A Wellenius; Charles B Eaton; Amal N Trivedi; Justin P Zachariah Journal: J Clin Lipidol Date: 2016-03-10 Impact factor: 4.766
Authors: Daniel J Conklin; Suzaynn Schick; Michael J Blaha; Alex Carll; Andrew DeFilippis; Peter Ganz; Michael E Hall; Naomi Hamburg; Tim O'Toole; Lindsay Reynolds; Sanjay Srivastava; Aruni Bhatnagar Journal: Am J Physiol Heart Circ Physiol Date: 2019-02-01 Impact factor: 4.733