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Nutrition, Metabolism, and... May 2021To systematically evaluate the evidence regarding the effects of foods on LDL cholesterol levels and to compare the findings with current guidelines. (Meta-Analysis)
Meta-Analysis
AIMS
To systematically evaluate the evidence regarding the effects of foods on LDL cholesterol levels and to compare the findings with current guidelines.
DATA SYNTHESIS
From inception through June 2019, we searched PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials for guidelines, systematic reviews, and RCTs (for coffee intake only) of at least 13 days duration. Additionally, we searched Trip database for guidelines from 2009 through Oct 2019. Language was restricted to English. The strength of evidence was evaluated using The Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A total of 37 guidelines, 108 systematic reviews, and 20 RCTs were included. With high evidence, foods high in unsaturated and low in saturated and trans fatty acids (e.g. rapeseed/canola oil), with added plant sterols/stanols, and high in soluble fiber (e.g. oats, barley, and psyllium) caused at least moderate (i.e. 0.20-0.40 mmol/L) reductions in LDL cholesterol. Unfiltered coffee caused a moderate to large increase. Soy protein, tomatoes, flaxseeds, and almonds caused small reductions. With moderate evidence, avocados and turmeric caused moderate to large reductions. Pulses, hazelnuts, walnuts, high-fiber/wholegrain foods, and green tea caused small to moderate reductions, whereas sugar caused a small increase. Other identified foods were either neutral or had low or very low evidence regarding their effects.
CONCLUSIONS
Several foods distinctly modify LDL cholesterol levels. The results may aid future guidelines and dietary advice for hypercholesterolemia.
Topics: Adult; Biomarkers; Cholesterol, LDL; Diet; Diet, Healthy; Down-Regulation; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Nutritive Value; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Risk Reduction Behavior; Treatment Outcome; Young Adult
PubMed: 33762150
DOI: 10.1016/j.numecd.2020.12.032 -
BMC Complementary Medicine and Therapies Jun 2021Elevated lipid profiles and impaired glucose homeostasis are risk factors for several cardiovascular diseases (CVDs), which, subsequently, represent a leading cause of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Elevated lipid profiles and impaired glucose homeostasis are risk factors for several cardiovascular diseases (CVDs), which, subsequently, represent a leading cause of early mortality, worldwide. The aim of the current study was to conduct a systematic review and meta-analysis of the effect of apple cider vinegar (ACV) on lipid profiles and glycemic parameters in adults.
METHODS
A systematic search was conducted in electronic databases, including Medline, Scopus, Cochrane Library, and Web of Knowledge, from database inception to January 2020. All clinical trials which investigated the effect of ACV on lipid profiles and glycemic indicators were included. Studies were excluded if ACV was used in combination with other interventions or when the duration of intervention was < 2 weeks. To account for between-study heterogeneity, we performed meta-analysis using a random-effects model.
RESULTS
Overall, nine studies, including 10 study arms, were included in this meta-analysis. We found that ACV consumption significantly decreased serum total cholesterol (- 6.06 mg/dL; 95% CI: - 10.95, - 1.17; I: 39%), fasting plasma glucose (- 7.97 mg/dL; 95% CI: - 13.74, - 2.21; I: 75%), and HbA1C concentrations (- 0.50; 95% CI: - 0.90, - 0.09; I: 91%). No significant effect of ACV consumption was found on serum LDL-C, HDL-C, fasting insulin concentrations, or HOMA-IR. The stratified analysis revealed a significant reduction of serum TC and TG in a subgroup of patients with type 2 diabetes, those who took ≤15 mL/day of ACV, and those who consumed ACV for > 8-weeks, respectively. Furthermore, ACV consumption significantly decreased FPG levels in a subgroup of studies that administered ACV for > 8-weeks. Further, ACV intake appeared to elicit an increase in FPG and HDL-C concentrations in apparently healthy participants.
CONCLUSION
We found a significant favorable effect of ACV consumption on FPG and blood lipid levels.
Topics: Acetic Acid; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Malus; Randomized Controlled Trials as Topic
PubMed: 34187442
DOI: 10.1186/s12906-021-03351-w -
BMJ (Clinical Research Ed.) Apr 2020To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement... (Meta-Analysis)
Meta-Analysis
Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials.
OBJECTIVE
To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese.
DESIGN
Systematic review and network meta-analysis of randomised trials.
DATA SOURCES
Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews.
STUDY SELECTION
Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet.
OUTCOMES AND MEASURES
Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up.
REVIEW METHODS
Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets.
RESULTS
121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty 7.08 mg/dL, moderate certainty 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (-1.88 mg/dL, moderate certainty) and moderate macronutrient (-0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared.
CONCLUSIONS
Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42015027929.
Topics: Blood Pressure; Body Mass Index; Body Weight; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Diet, Mediterranean; Humans; Network Meta-Analysis; Nutrients; Obesity; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Weight Loss
PubMed: 32238384
DOI: 10.1136/bmj.m696 -
International Journal of Environmental... Jul 2022Numerous studies have demonstrated that abnormal levels of cholesterol are associated with a high attributable risk for the occurrence of cardiovascular disease (CVD).... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Numerous studies have demonstrated that abnormal levels of cholesterol are associated with a high attributable risk for the occurrence of cardiovascular disease (CVD). However, there has been no comprehensive study to investigate the relationship between serum cholesterol levels and cardiovascular mortality. Therefore, we conducted a systematic review and dose-response meta-analysis.
METHODS
A systematic literature search of key databases, including EMBASE and MEDLINE, was conducted and included all the published epidemiological studies that contained estimates of the hazard ratios (HR) of serum cholesterol of CVD mortality. Data extraction, eligibility, and assessment of the risk of bias were assessed by two reviewers independently. All published risk estimates were hazard ratios and analyzed by quantitative meta-analysis using a random-effects model and dose-response relationships of serum cholesterol with CVD mortality.
RESULTS
A total of 14 independent reports, including 1,055,309 subjects and 9457 events, were analyzed. The pooled HR (95% CI) was 1.27 (95% CI, 1.19-1.36) for total cholesterol, 1.21 (95% CI, 1.09-1.35) for low-density lipoprotein cholesterol (LDL-C), and 0.60 (95% CI, 0.50-0.72) for high-density lipoprotein cholesterol (HDL-C). We observed a linear association between serum cholesterol (TC, HDL-C) levels and CVD mortality in this meta-analysis.
CONCLUSIONS
Serum total cholesterol and LDL-C level is associated with increased CVD mortality, but HDL-C level is inversely associated with CVD mortality.
Topics: Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Humans; Prospective Studies; Risk Factors; Triglycerides
PubMed: 35886124
DOI: 10.3390/ijerph19148272 -
JAMA Internal Medicine May 2022The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than... (Meta-Analysis)
Meta-Analysis
Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis.
IMPORTANCE
The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear.
OBJECTIVE
To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy.
DATA SOURCES
PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021.
STUDY SELECTION
Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years.
DATA EXTRACTION AND SYNTHESIS
Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken.
MAIN OUTCOMES AND MEASURES
Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke.
FINDINGS
Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive.
CONCLUSIONS AND RELEVANCE
The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.
Topics: Cardiovascular Diseases; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Myocardial Infarction; Randomized Controlled Trials as Topic; Stroke
PubMed: 35285850
DOI: 10.1001/jamainternmed.2022.0134 -
The American Journal of Clinical... Aug 2015Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD), which has led to US recommendations to reduce cholesterol intake. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD), which has led to US recommendations to reduce cholesterol intake.
OBJECTIVE
The authors examine the effects of dietary cholesterol on CVD risk in healthy adults by using systematic review and meta-analysis.
DESIGN
MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau Abstracts databases were searched through December 2013 for prospective studies that quantified dietary cholesterol. Investigators independently screened citations and verified extracted data on study and participant characteristics, outcomes, and quality. Random-effect models meta-analysis was used when at least 3 studies reported the same CVD outcome.
RESULTS
Forty studies (17 cohorts in 19 publications with 361,923 subjects and 19 trials in 21 publications with 632 subjects) published between 1979 and 2013 were eligible for review. Dietary cholesterol was not statistically significantly associated with any coronary artery disease (4 cohorts; no summary RR), ischemic stroke (4 cohorts; summary RR: 1.13; 95% CI: 0.99, 1.28), or hemorrhagic stroke (3 cohorts; summary RR: 1.09; 95% CI: 0.79, 1.50). Dietary cholesterol statistically significantly increased both serum total cholesterol (17 trials; net change: 11.2 mg/dL; 95% CI: 6.4, 15.9) and low-density lipoprotein (LDL) cholesterol (14 trials; net change: 6.7 mg/dL; 95% CI: 1.7, 11.7 mg/dL). Increases in LDL cholesterol were no longer statistically significant when intervention doses exceeded 900 mg/d. Dietary cholesterol also statistically significantly increased serum high-density lipoprotein cholesterol (13 trials; net change: 3.2 mg/dL; 95% CI: 0.9, 9.7 mg/dL) and the LDL to high-density lipoprotein ratio (5 trials; net change: 0.2; 95% CI: 0.0, 0.3). Dietary cholesterol did not statistically significantly change serum triglycerides or very-low-density lipoprotein concentrations.
CONCLUSION
Reviewed studies were heterogeneous and lacked the methodologic rigor to draw any conclusions regarding the effects of dietary cholesterol on CVD risk. Carefully adjusted and well-conducted cohort studies would be useful to identify the relative effects of dietary cholesterol on CVD risk.
Topics: Brain Ischemia; Cardiovascular Diseases; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Evidence-Based Medicine; Hemorrhagic Disorders; Humans; Non-Randomized Controlled Trials as Topic; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk Factors; Stroke
PubMed: 26109578
DOI: 10.3945/ajcn.114.100305 -
BMJ Open Jun 2016It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is... (Review)
Review
OBJECTIVE
It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.
SETTING, PARTICIPANTS AND OUTCOME MEASURES
We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.
RESULTS
We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.
CONCLUSIONS
High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.
Topics: Aged; Cardiovascular Diseases; Cholesterol, LDL; Humans; Middle Aged; Mortality; Risk Factors
PubMed: 27292972
DOI: 10.1136/bmjopen-2015-010401 -
The International Journal of Behavioral... Jul 2018Current international guidelines recommend aerobic, resistance, and combined exercises for the management of type 2 diabetes mellitus (T2DM). In our study, we conducted... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Current international guidelines recommend aerobic, resistance, and combined exercises for the management of type 2 diabetes mellitus (T2DM). In our study, we conducted a network meta-analysis to assess the comparative impact of different exercise training modalities on glycemic control, cardiovascular risk factors, and weight loss in patients with T2DM.
METHODS
We searched five electronic databases to identify randomized controlled trials (RCTs) that compared the differences between different exercise training modalities for patients with T2DM. The risk of bias in the included RCTs was evaluated according to the Cochrane tool. Network meta-analysis was performed to calculate mean difference the ratio of the mean and absolute risk differences. Data were analyzed using R-3.4.0.
RESULTS
A total of 37 studies with 2208 patients with T2DM were included in our study. Both supervised aerobic and supervised resistance exercises showed a significant reduction in HbA1c compared to no exercise (0.30% lower, 0.30% lower, respectively), however, there was a less reduction when compared to combined exercise (0.17% higher, 0.23% higher). Supervised aerobic also presented more significant improvement than no exercise in fasting plasma glucose (9.38 mg/dl lower), total cholesterol (20.24 mg/dl lower), triacylglycerol (19.34 mg/dl lower), and low-density lipoprotein cholesterol (11.88 mg/dl lower). Supervised resistance showed more benefit than no exercise in improving systolic blood pressure (3.90 mmHg lower]) and total cholesterol (22.08 mg/dl lower]. In addition, supervised aerobic exercise was more powerful in improving HbA1c and weight loss than unsupervised aerobic (HbA1c: 0.60% lower; weight loss: 5.02 kg lower) and unsupervised resistance (HbA1c: 0.53% lower) exercises.
CONCLUSION
Compared with either supervised aerobic or supervised resistance exercise alone, combined exercise showed more pronounced improvement in HbA1c levels; however, there was a less marked improvement in some cardiovascular risk factors. In terms of weight loss, there were no significant differences among the combined, supervised aerobic, and supervised resistance exercises.
TRIAL REGISTRATION
Our study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42017067518 .
Topics: Aged; Blood Glucose; Blood Pressure; Cholesterol, LDL; Diabetes Mellitus, Type 2; Exercise; Exercise Therapy; Female; Glycated Hemoglobin; Humans; Lipids; Male; Middle Aged; Network Meta-Analysis; Resistance Training; Weight Loss
PubMed: 30045740
DOI: 10.1186/s12966-018-0703-3 -
Nutrients Dec 2020The rise in obesity has emphasised a focus on lifestyle and dietary habits. We aimed to address the debate between low-carbohydrate and low-fat diets and compare their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The rise in obesity has emphasised a focus on lifestyle and dietary habits. We aimed to address the debate between low-carbohydrate and low-fat diets and compare their effects on body weight, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol, and triglycerides in an adult population.
METHOD
Medline and Web of Science were searched for randomised controlled trials (RCTs) comparing low-fat and low-carbohydrate diets up to September 2019. Three independent reviewers extracted data. Risk of bias was assessed using the Cochrane tool. The meta-analysis was stratified by follow-up time using the random-effects models.
RESULTS
This meta-analysis of 38 studies assessed a total of 6499 adults. At 6-12 months, pooled analyses of mean differences of low-carbohydrate vs. low-fat diets favoured the low-carbohydrate diet for average weight change (mean difference -1.30 kg; 95% CI -2.02 to -0.57), HDL (0.05 mmol/L; 95% CI 0.03 to 0.08), and triglycerides (TG) (-0.10 mmol/L; -0.16 to -0.04), and favoured the low-fat diet for LDL (0.07 mmol/L; 95% CI 0.02 to 0.12) and total cholesterol (0.10 mmol/L; 95% CI 0.02 to 0.18). Conclusion and Relevance: This meta-analysis suggests that low-carbohydrate diets are effective at improving weight loss, HDL and TG lipid profiles. However, this must be balanced with potential consequences of raised LDL and total cholesterol in the long-term.
Topics: Adult; Cholesterol, HDL; Cholesterol, LDL; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Humans; Lipids; Triglycerides; Weight Loss
PubMed: 33317019
DOI: 10.3390/nu12123774 -
JAMA Apr 2018Effects on specific fatal and nonfatal end points appear to vary for low-density lipoprotein cholesterol (LDL-C)-lowering drug trials. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Effects on specific fatal and nonfatal end points appear to vary for low-density lipoprotein cholesterol (LDL-C)-lowering drug trials.
OBJECTIVE
To evaluate whether baseline LDL-C level is associated with total and cardiovascular mortality risk reductions.
DATA SOURCESAND STUDY SELECTION
Electronic databases (Cochrane, MEDLINE, EMBASE, TCTMD, ClinicalTrials.gov, major congress proceedings) were searched through February 2, 2018, to identify randomized clinical trials of statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies.
DATA EXTRACTION AND SYNTHESIS
Two investigators abstracted data and appraised risks of bias. Intervention groups were categorized as "more intensive" (more potent pharmacologic intervention) or "less intensive" (less potent, placebo, or control group).
MAIN OUTCOMES AND MEASURES
The coprimary end points were total mortality and cardiovascular mortality. Random-effects meta-regression and meta-analyses evaluated associations between baseline LDL-C level and reductions in mortality end points and secondary end points including major adverse cardiac events (MACE).
RESULTS
In 34 trials, 136 299 patients received more intensive and 133 989 received less intensive LDL-C lowering. All-cause mortality was lower for more vs less intensive therapy (7.08% vs 7.70%; rate ratio [RR], 0.92 [95% CI, 0.88 to 0.96]), but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with greater reductions in all-cause mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.91 [95% CI, 0.86 to 0.96]; P = .001; absolute risk difference [ARD], -1.05 incident cases per 1000 person-years [95% CI, -1.59 to -0.51]), but only when baseline LDL-C levels were 100 mg/dL or greater (P < .001 for interaction) in a meta-analysis. Cardiovascular mortality was lower for more vs less intensive therapy (3.48% vs 4.07%; RR, 0.84 [95% CI, 0.79 to 0.89]) but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with a greater reduction in cardiovascular mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.86 [95% CI, 0.80 to 0.94]; P < .001; ARD, -1.0 incident cases per 1000 person-years [95% CI, -1.51 to -0.45]), but only when baseline LDL-C levels were 100 mg/dL or greater (P < .001 for interaction) in a meta-analysis. Trials with baseline LDL-C levels of 160 mg/dL or greater had the greatest reduction in all-cause mortality (RR, 0.72 [95% CI, 0.62 to 0.84]; P < .001; 4.3 fewer deaths per 1000 person-years) in a meta-analysis. More intensive LDL-C lowering was also associated with progressively greater risk reductions with higher baseline LDL-C level for myocardial infarction, revascularization, and MACE.
CONCLUSIONS AND RELEVANCE
In these meta-analyses and meta-regressions, more intensive compared with less intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels. This association was not present when baseline LDL-C level was less than 100 mg/dL, suggesting that the greatest benefit from LDL-C-lowering therapy may occur for patients with higher baseline LDL-C levels.
Topics: Antibodies, Monoclonal; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Confounding Factors, Epidemiologic; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mortality; PCSK9 Inhibitors; Regression Analysis; Risk
PubMed: 29677301
DOI: 10.1001/jama.2018.2525