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Can dementia risk be reduced by following the American Heart Association's Life's Simple 7? A systematic review and dose-response meta-analysis.
Wu, J, Xiong, Y, Xia, X, Orsini, N, Qiu, C, Kivipelto, M, Rizzuto, D, Wang, R
Ageing research reviews. 2023;83:101788
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Plain language summary
The American Heart Association (AHA) has defined ideal levels of seven modifiable cardiovascular health (CVH) factors, known as Life's Simple 7, that consist of smoking, physical activity, diet, body mass index, fasting blood glucose, total cholesterol, and blood pressure. Maintaining ideal levels of these factors has been recommended as a prevention strategy against not only cardiovascular diseases but also neurodegenerative disorders, e.g., cognitive decline and dementia. However, studies exploring the beneficial effects of the AHA’s CVH metrics on cognitive outcomes, especially among older populations, have been uncertain, and solid evidence is lacking in this field. This systematic review and meta-analysis aimed to quantify the relationship between the AHA’s CVH metrics and cognitive outcomes. 14 longitudinal studies were included in the meta-analysis. The results showed a considerable effect of a favourable total CVH score on reduced risk of incident dementia in adults aged 70 years or older. When looking at the individual factors, dementia risk can be reduced significantly if older adults achieved the recommended level of physical activity, blood glucose, or total cholesterol. The association with smoking appeared to be borderline, and there was no association between diet, body mass index hazard ratio or blood pressure and dementia risk. The authors concluded that their findings provide evidence that maintaining a favourable level of CVH score, either in mid- or late- life, would substantially reduce the risk of dementia among older adults. Preserving cardiovascular health by quitting smoking, engaging in physical exercise, controlling blood glucose and total cholesterol might be especially effective for forestalling cognitive decline and dementia.
Abstract
This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.
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Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis.
Velásquez, IM, Malarstig, A, Baldassarre, D, Borne, Y, de Faire, U, Engström, G, Eriksson, P, Giral, P, Humphries, SE, Kurl, S, et al
Current research in translational medicine. 2023;(1):103374
Abstract
BACKGROUND We investigated the causality of IL-8 on carotid intima-media thickness (c-IMT), a measure of sub-clinical atherosclerosis. METHODS The IMPROVE is a multicenter European study (n = 3,711). The association of plasma IL-8 with c-IMT (mm) was estimated by quantile regression. Genotyping was performed using the Illumina CardioMetabo and Immuno chips. Replication was attempted in three independent studies and a meta-analysis was performed using a random model. RESULTS In IMPROVE, each unit increase in plasma IL-8 was associated with an increase in median c-IMT measures (all p<0·03) in multivariable analyses. Linear regression identified rs117518778 and rs8057084 as associated with IL-8 levels and with measures of c-IMT. The two SNPs were combined in an IL-8-increasing genetic risk that showed causality of IL-8 on c-IMT in IMPROVE and in the UK Biobank (n = 22,179). The effect of IL-8 on c-IMT measures was confirmed in PIVUS (n = 1,016) and MDCCC (n = 6,103). The association of rs8057084 with c-IMT was confirmed in PIVUS and UK Biobank with a pooled estimate effect (β) of -0·006 with 95%CI (-0·008- -0·003). CONCLUSION Our results indicate that genetic variants associated with plasma IL-8 also associate with c-IMT. However, we cannot infer causality of this association, as these variants lie outside of the IL8 locus.
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Response by Filippini et al to Letter Regarding Article, "Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies".
Filippini, T, Malavolti, M, Whelton, PK, Naska, A, Orsini, N, Vinceti, M
Circulation. 2021;(15):e237
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Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies.
Filippini, T, Malavolti, M, Whelton, PK, Naska, A, Orsini, N, Vinceti, M
Circulation. 2021;(16):1542-1567
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Abstract
BACKGROUND The relationship between dietary sodium intake and blood pressure (BP) has been tested in clinical trials and nonexperimental human studies, indicating a direct association. The exact shape of the dose-response relationship has been difficult to assess in clinical trials because of the lack of random-effects dose-response statistical models that can include 2-arm comparisons. METHODS After performing a comprehensive literature search for experimental studies that investigated the BP effects of changes in dietary sodium intake, we conducted a dose-response meta-analysis using the new 1-stage cubic spline mixed-effects model. We included trials with at least 4 weeks of follow-up; 24-hour urinary sodium excretion measurements; sodium manipulation through dietary change or supplementation, or both; and measurements of systolic and diastolic BP at the beginning and end of treatment. RESULTS We identified 85 eligible trials with sodium intake ranging from 0.4 to 7.6 g/d and follow-up from 4 weeks to 36 months. The trials were conducted in participants with hypertension (n=65), without hypertension (n=11), or a combination (n=9). Overall, the pooled data were compatible with an approximately linear relationship between achieved sodium intake and mean systolic as well as diastolic BP, with no indication of a flattening of the curve at either the lowest or highest levels of sodium exposure. Results were similar for participants with or without hypertension, but the former group showed a steeper decrease in BP after sodium reduction. Intervention duration (≥12 weeks versus 4 to 11 weeks), type of study design (parallel or crossover), use of antihypertensive medication, and participants' sex had little influence on the BP effects of sodium reduction. Additional analyses based on the BP effect of difference in sodium exposure between study arms at the end of the trial confirmed the results on the basis of achieved sodium intake. CONCLUSIONS In this dose-response analysis of sodium reduction in clinical trials, we identified an approximately linear relationship between sodium intake and reduction in both systolic and diastolic BP across the entire range of dietary sodium exposure. Although this occurred independently of baseline BP, the effect of sodium reduction on level of BP was more pronounced in participants with a higher BP level.
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Cadmium exposure and risk of breast cancer: A dose-response meta-analysis of cohort studies.
Filippini, T, Torres, D, Lopes, C, Carvalho, C, Moreira, P, Naska, A, Kasdagli, MI, Malavolti, M, Orsini, N, Vinceti, M
Environment international. 2020;:105879
Abstract
BACKGROUND Cadmium is a toxic heavy metal that has been implicated in breast cancer etiology, albeit with inconsistent results. OBJECTIVE To investigate the shape of the relation between cadmium exposure and breast cancer incidence and mortality in cohort studies. DATA SOURCES Following a literature search through April 14, 2020, we carried out a systematic review and dose-response meta-analysis to investigate the shape of the relation between cadmium exposure (assessed either through diet or urine excretion) and disease incidence and mortality. STUDY ELIGIBILITY CRITERIA For inclusion, a study had to report incidence or mortality for breast cancer according to baseline cadmium exposure category; be a prospective cohort, case-cohort or nested case-control study with a minimum one-year follow-up, and reporting effect estimates for all exposure categories. STUDY APPRAISAL AND SYNTHESIS METHODS Studies were evaluated using the ROBINS-E risk of bias tool. The effects in humans were assessed quantitatively using one-stage dose-response meta-analysis in a random effects meta-analytical model. RESULTS We identified 10 studies eligible for inclusion in the dose-response meta-analysis, six based on cadmium dietary intake, and four on urinary excretion levels. We found a marginal and imprecise positive relation between dietary cadmium intake and breast cancer, and no association when urinary cadmium excretion was used for exposure assessment. Compared to no exposure, at 20 µg/day of cadmium intake the summary risk ratio was 1.12 (95% confidence interval 0.80-1.56), while at 2 µg/g creatinine of cadmium excretion the summary risk ratio was 0.89 (95% confidence interval 0.38-2.14). Analysis restricted to post-menopausal women showed no association between either dietary or urinary cadmium and subsequent breast cancer incidence and mortality. LIMITATIONS AND CONCLUSIONS Overall, we found scant evidence of a positive association between cadmium and breast cancer. Available data were too limited to carry out stratified analyses according to age, smoking and hormone receptor status. Therefore, possible associations between cadmium exposure and breast cancer in selected subgroups cannot be entirely ruled out.
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Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials.
Filippini, T, Naska, A, Kasdagli, MI, Torres, D, Lopes, C, Carvalho, C, Moreira, P, Malavolti, M, Orsini, N, Whelton, PK, et al
Journal of the American Heart Association. 2020;(12):e015719
Abstract
Background Epidemiologic studies, including trials, suggest an association between potassium intake and blood pressure (BP). However, the strength and shape of this relationship is uncertain. Methods and Results We performed a meta-analysis to explore the dose-response relationship between potassium supplementation and BP in randomized-controlled trials with a duration ≥4 weeks using the recently developed 1-stage cubic spline regression model. This model allows use of trials with at least 2 exposure categories. We identified 32 eligible trials. Most were conducted in adults with hypertension using a crossover design and potassium supplementation doses that ranged from 30 to 140 mmol/d. We observed a U-shaped relationship between 24-hour active and control arm differences in potassium excretion and BP levels, with weakening of the BP reduction effect above differences of 30 mmol/d and a BP increase above differences ≈80 mmol/d. Achieved potassium excretion analysis also identified a U-shaped relationship. The BP-lowering effects of potassium supplementation were stronger in participants with hypertension and at higher levels of sodium intake. The BP increase with high potassium excretion was noted in participants with antihypertensive drug-treated hypertension but not in their untreated counterparts. Conclusions We identified a nonlinear relationship between potassium intake and both systolic and diastolic BP, although estimates for BP effects of high potassium intakes should be interpreted with caution because of limited availability of trials. Our findings indicate an adequate intake of potassium is desirable to achieve a lower BP level but suggest excessive potassium supplementation should be avoided, particularly in specific subgroups.
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Association between Outdoor Air Pollution and Childhood Leukemia: A Systematic Review and Dose-Response Meta-Analysis.
Filippini, T, Hatch, EE, Rothman, KJ, Heck, JE, Park, AS, Crippa, A, Orsini, N, Vinceti, M
Environmental health perspectives. 2019;(4):46002
Abstract
BACKGROUND A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose-response relation. OBJECTIVE We investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia. METHODS We searched all case-control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose-response curve using a restricted cubic spline regression model. RESULTS We found 29 studies eligible to be included in our review. In the dose-response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels. DISCUSSION Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381.
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Coffee Consumption and Risk of Dementia and Alzheimer's Disease: A Dose-Response Meta-Analysis of Prospective Studies.
Larsson, SC, Orsini, N
Nutrients. 2018;(10)
Abstract
Coffee consumption is associated with a reduced risk of several diseases but uncertainty remains about the influence of coffee consumption on the risk of dementia. We performed a dose-response meta-analysis to summarize the prospective data on coffee consumption and associated risk of dementia and Alzheimer's disease. We identified studies by searching PubMed (from January 1966) and Web of Science (from January 1945) through 4 October 2018 and by scrutinizing the reference lists of pertinent publications. Two researchers independently reviewed the literature. Results were combined using a restricted cubic spline random-effects dose-response meta-analysis based on a one-stage approach. Eight relevant prospective studies were identified. These studies included 7486 dementia cases diagnosed among 328,885 individuals during an average follow-up of 4.9⁻25 years. Meta-analysis of all eight studies indicated no statistically significant association between coffee consumption and the risk of dementia and no deviations from a linear trend (p = 0.08). The relative risk of dementia per 1 cup/day increment of coffee consumption was 1.01 (95% confidence interval (CI) 0.98⁻1.05; p = 0.37). Meta-analysis of five studies that focused on Alzheimer's disease revealed no association between coffee consumption and Alzheimer's disease and no deviations from a linear trend (p = 0.79). The relative risk of Alzheimer's disease per 1 cup/day increment of coffee consumption was 1.01 (95% confidence interval 0.95⁻1.07; p = 0.80). These results do not support an association between coffee consumption and an increased risk of overall dementia or Alzheimer's disease specifically, but further research on the association of coffee consumption with dementia risk is needed.
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Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium.
Ordóñez-Mena, JM, Schöttker, B, Mons, U, Jenab, M, Freisling, H, Bueno-de-Mesquita, B, O'Doherty, MG, Scott, A, Kee, F, Stricker, BH, et al
BMC medicine. 2016;:62
Abstract
BACKGROUND Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality. METHODS This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs. RESULTS Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking. CONCLUSIONS This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.
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Meta-Analysis of Potassium Intake and the Risk of Stroke.
Vinceti, M, Filippini, T, Crippa, A, de Sesmaisons, A, Wise, LA, Orsini, N
Journal of the American Heart Association. 2016;(10)
Abstract
BACKGROUND The possibility that lifestyle factors such as diet, specifically potassium intake, may modify the risk of stroke has been suggested by several observational cohort studies, including some recent reports. We performed a systematic review and meta-analysis of existing studies and assessed the dose-response relation between potassium intake and stroke risk. METHODS AND RESULTS We reviewed the observational cohort studies addressing the relation between potassium intake, and incidence or mortality of total stroke or stroke subtypes published through August 6, 2016. We carried out a meta-analysis of 16 cohort studies based on the relative risk (RR) of stroke comparing the highest versus lowest intake categories. We also plotted a pooled dose-response curve of RR of stroke according to potassium intake. Analyses were performed with and without adjustment for blood pressure. Relative to the lowest category of potassium intake, the highest category of potassium intake was associated with a 13% reduced risk of stroke (RR=0.87, 95% CI 0.80-0.94) in the blood pressure-adjusted analysis. Summary RRs tended to decrease when original estimates were unadjusted for blood pressure. Analysis for stroke subtypes yielded comparable results. In the spline analysis, the pooled RR was lowest at 90 mmol of potassium daily intake (RRs=0.78, 95% CI 0.70-0.86) in blood pressure-adjusted analysis, and 0.67 (95% CI 0.57-0.78) in unadjusted analysis. CONCLUSIONS Overall, this dose-response meta-analysis confirms the inverse association between potassium intake and stroke risk, with potassium intake of 90 mmol (≈3500 mg)/day associated with the lowest risk of stroke.