Effect of Long-Term Exposure to Lower Low-Density Lipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease A Mendelian Randomization Analysis

ObjectivesThe 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).BackgroundLDL-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.MethodsWe 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.ResultsAll 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 (I2 = 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).ConclusionsProlonged 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

A comparative study between PGE1 and PGE2 for induction of labour in premature rupture of membrane at term

Background: Premature rupture of membranes at term can be managed expectantly with good results. However, low bishop score may lead to undue latency. It can lead to complications if no intervention done. So, timely intervention by labour induction in selected cases can improve maternal and fetal outcome. Prostaglandins has very vital role for induction of labour. This study is to compare the effectiveness between the two molecules of prostaglandins PGE1 and PGE2 for induction of labour in term premature rupture of membrane (PROM).Methods: It is a prospective interventional study performed at a tertiary hospital attached to a medical college. It was conducted upon randomly selected 100 women of term PROM from April 2011 to April 2015. They were divided into two comparable groups each containing 50 women. Both the groups were comparable in age, parity and bishop score. One group was induced with PGE1 (Tab Misoprostol) and the other with PGE2 (Dinoprostone gel).Results: Among 100 women, a good number of women were primigravida (76%). Majority of women were induced in between 6 to 12 hours after PROM (69%). Vaginal deliveries were 68% in tab. Misoprostol group while 80% in dinoprostone gel group which are comparable in both the groups. The significant difference observed was average induction delivery interval, which was 11.26 hours in tab. misoprostol group and 14.72 hours in dinoprostone gel group (P=0.004). The other women (26%) underwent cesarean section. Among them 46.15% were done for fetal distress and 43.84% for induction failure.Conclusions: Both the molecules of prostaglandins are efficient for labour induction in term PROM.  Though, PGE1 (tab. Misoprostol) is faster acting as compare to PGE2 (dinoprostone gel) even with low bishop score. But it can lead to complications like hyperstimulation, fetal distress and postpartum hemorrhage if not used properly. So, tab misoprostol is not a safe drug where continuous monitoring of women is not available

Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: A mendelian randomization analysis

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 (I2 = 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. © 2012 American College of Cardiology Foundation