Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomised factorial trial

Gupta, Ajay; Mackay, Judith; Whitehouse, Andrew J. O.; Godec, Thomas; Collier, Tim; Pocock, Stuart J.; Poulter, Neil; Sever, Peter

doi:10.1016/s0140-6736(18)31776-8

Cited by 97 publications

(66 citation statements)

References 39 publications

(31 reference statements)

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“…What's more, it has been proven that high levels of plasma TC and LDL could increase the risk of CVD, while plasma HDL level is a protective biomarker of CVD (Ference et al., ; Rosenson et al., ). Overall, lowering plasma cholesterol level shows a long‐term beneficial effect on cardiovascular disease (Gupta et al., ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Genistein on Cholesterol Metabolism‐Related Genes in HepG2 Cell

Zheng

Yin

et al. 2019

Journal of Food Science

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It has been reported that genistein could improve metabolic syndromes. Our study aimed to investigate the effects and potential mechanisms of genistein on improving cholesterol metabolism in HepG2 cell. HepG2 cells were cultured with 0, 0.01, 1.00, 10.00, and 50.00 µM genistein for 24 hr. The current results showed a dose‐dependent manner between genistein and intracellular contents of total cholesterol (TC), high‐density lipoprotein‐cholesterol (HDL‐C), and cellular apolipoprotein A1 (Apo‐A1) secretion. TC was increased by 25.69%, meanwhile HDL‐C and Apo‐A1 were decreased by 56.00% and 25.93%, respectively, when the dosage of genistein was 1.00 µM. Genistein dose‐dependently upregulated the protein and mRNA levels of sterol regulatory element binding proteins‐2 (SREBP‐2), as well as the mRNA levels of low‐density lipoprotein receptor (LDLR) and 3‐hydroxy‐3‐methyl glutaryl coenzyme A reductase (HMGCR), by 145.91%, 72.29%, 310.23%, and 123.08%, respectively, when we gave 1.00 µM genistein, indicating that intracellular cholesterol synthesis and absorption of exogenous cholesterol were increased. In addition, the mRNA levels of peroxisome proliferator‐activated receptor‐γ (PPARγ) and liver X receptor (LXRα), lowered by 58.23% and 34.86% at 0.01 µM genistein, were reduced in a dose‐dependent manner. LXRα and ATP‐binding cassette transporter A1 (ABCA1) protein levels were significantly (P < 0.05) decreased by 50.35% and 11.60% at 1.00 µM genistein, which indicated that cellular cholesterol efflux was inhibited. Taken together, our results suggested that genistein at dosage of more than 1.00 µM was able to increase the intracellular cholesterol levels by up regulating SREBP‐2/LDLR/HMGCR pathway and suppressing PPARγ/LXRα/ABCA1 pathway. Practical Application In this study, genistein appeared to be effective in reducing plasma cholesterol levels due to increase the intracellular cholesterol levels by upregulating cholesterol absorption through SREBP‐2/LDLR/HMGCR pathway, and also downregulating cholesterol efflux via PPARγ/LXRα/ABCA1 pathway in vitro. In addition, plasma cholesterol is regarded as the key indicator of atherosclerosis; therefore, we believe that our findings could be used for further exploration on a possible therapeutic application of genistein for atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

Effect of Genistein on Cholesterol Metabolism‐Related Genes in HepG2 Cell

Zheng

Yin

et al. 2019

Journal of Food Science

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“…These results could suggest that not all hypotensive drugs are equally effective in preventing CVD, although the resulting BPs are similar. After 16 years of total follow-up (ASCOT Legacy Study), there was no overall difference in all-cause mortality between treatments, although significantly fewer deaths from stroke (HR 0.71, 95% CI, 0.53-0.97) occurred in the amlodipine-based treatment group (Table 2) [53].…”

Section: Legacy Effect After Blood Pressure Controlmentioning

confidence: 99%

The Legacy Effect in the Prevention of Cardiovascular Disease

2020

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The “legacy effect” describes the long-term benefits that may persist for many years after the end of an intervention period, involving different biological processes. The legacy effect in cardiovascular disease (CVD) prevention has been evaluated by a limited number of studies, mostly based on pharmacological interventions, while few manuscripts on dietary interventions have been published. Most of these studies are focused on intensive treatment regimens, whose main goal is to achieve tight control of one or more cardiovascular risk factors. This review aims to summarise the legacy effect-related results obtained in those studies and to determine the existence of this effect in CVD prevention. There is sufficient data to suggest the existence of a legacy effect after intensive intervention on cardiovascular risk factors; however, this effect is not equivalent for all risk factors and could be influenced by patient characteristics, disease duration, and the type of intervention performed. Currently, available evidence suggests that the legacy effect is greater in subjects with moderately-high cardiovascular risk but without CVD, especially in those patients with recent-onset diabetes. However, preventive treatment for CVD should not be discontinued in high-risk subjects, as the level of existing evidence on the legacy effect is low to moderate.

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“…Overall, the addition of atorvastatin to the amlodipine plus perindopril combination offered greater cardiovascular protection versus atenolol plus bendroflumethiazide plus atorvastatin therapy, with a 24% reduction in total cardiovascular events and procedures, a 31% reduction in total coronary events, a 39% reduction in the composite of non-fatal MI/fatal CHD/coronary revascularization, and a 42% reduction in the composite of cardiovascular mortality/MI/stroke [38]. Longterm follow-up data from ASCOT-LLA was collected 16 years after randomization and demonstrated continued benefits of an amlodipine plus perindopril based regimen on stroke death (29% reduction vs atenolol plus bendroflumethiazide) and cardiovascular death (21% reduction vs atenolol plus bendroflumethiazide), as well as benefits of the addition of atorvastatin on cardiovascular death (15% reduction versus placebo) [39].…”

Section: Efficacy Of Combination Therapy With Amlodipine Perindoprilmentioning

confidence: 99%