IMPORTANCE: Low-dose aspirin is used for primary cardiovascular disease prevention and may have benefits for colorectal cancer prevention. OBJECTIVE: To review the benefits and harms of aspirin in ...primary cardiovascular disease prevention and colorectal cancer prevention to inform the US Preventive Services Task Force. DATA SOURCES: MEDLINE, PubMed, Embase, and the Cochrane Central Register of Controlled Trials through January 2021; literature surveillance through January 21, 2022. STUDY SELECTION: English-language randomized clinical trials (RCTs) of low-dose aspirin (≤100 mg/d) compared with placebo or no intervention in primary prevention populations. DATA EXTRACTION AND SYNTHESIS: Single extraction, verified by a second reviewer. Quantitative synthesis using Peto fixed-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Cardiovascular disease events and mortality, all-cause mortality, colorectal cancer incidence and mortality, major bleeding, and hemorrhagic stroke. RESULTS: Eleven RCTs (N = 134 470) and 1 pilot trial (N = 400) of low-dose aspirin for primary cardiovascular disease prevention were included. Low-dose aspirin was associated with a significant decrease in major cardiovascular disease events (odds ratio OR, 0.90 95% CI, 0.85-0.95; 11 RCTs n = 134 470; I2 = 0%; range in absolute effects, −2.5% to −0.1%). Results for individual cardiovascular disease outcomes were significant, with similar magnitude of benefit. Aspirin was not significantly associated with reductions in cardiovascular disease mortality or all-cause mortality. There was limited trial evidence on benefits for colorectal cancer, with the findings highly variable by length of follow-up and statistically significant only when considering long-term observational follow-up beyond randomized trial periods. Low-dose aspirin was associated with significant increases in total major bleeding (OR, 1.44 95% CI, 1.32-1.57; 10 RCTs n = 133 194; I2 = 4.7%; range in absolute effects, 0.1% to 1.0%) and in site-specific bleeding, with similar magnitude. CONCLUSIONS AND RELEVANCE: Low-dose aspirin was associated with small absolute risk reductions in major cardiovascular disease events and small absolute increases in major bleeding. Colorectal cancer results were less robust and highly variable.
IMPORTANCE: Incorporating nontraditional risk factors may improve the performance of traditional multivariable risk assessment for cardiovascular disease (CVD). OBJECTIVE: To systematically review ...evidence for the US Preventive Services Task Force on the benefits and harms of 3 nontraditional risk factors in cardiovascular risk assessment: the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, and coronary artery calcium (CAC) score. DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for studies published through May 22, 2017. Surveillance continued through February 7, 2018. STUDY SELECTION: Studies of asymptomatic adults with no known cardiovascular disease. DATA EXTRACTION AND SYNTHESIS: Independent critical appraisal and data abstraction by 2 reviewers. MAIN OUTCOMES AND MEASURES: Cardiovascular events, mortality, risk assessment performance measures (calibration, discrimination, or risk reclassification), and serious adverse events. RESULTS: Forty-three studies (N = 267 244) were included. No adequately powered trials have evaluated the clinical effect of risk assessment with nontraditional risk factors on patient health outcomes. The addition of the ABI (10 studies), hsCRP level (25 studies), or CAC score (19 studies) can improve both discrimination and reclassification; the magnitude and consistency of improvement varies by nontraditional risk factor. For the ABI, improvements in performance were the greatest for women, in whom traditional risk assessment has poor discrimination (C statistic change of 0.112 and net reclassification index NRI of 0.096). Results were inconsistent for hsCRP level, with the largest analysis (n = 166 596) showing a minimal effect on risk prediction (C statistic change of 0.0039, NRI of 0.0152). The largest improvements in discrimination (C statistic change ranging from 0.018 to 0.144) and reclassification (NRI ranging from 0.084 to 0.35) were seen for CAC score, although CAC score may inappropriately reclassify individuals not having cardiovascular events into higher-risk categories, as determined by negative nonevent NRI. Evidence for the harms of nontraditional risk factor assessment was limited to computed tomography imaging for CAC scoring (8 studies) and showed that radiation exposure is low but may result in additional testing. CONCLUSIONS AND RELEVANCE: There are insufficient adequately powered clinical trials evaluating the incremental effect of the ABI, hsCRP level, or CAC score in risk assessment and initiation of preventive therapy. Furthermore, the clinical meaning of improvements in measures of calibration, discrimination, and reclassification risk prediction studies is uncertain.
IMPORTANCE: Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood. OBJECTIVE: To ...systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force. DATA SOURCES: MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites. Surveillance continued through December 5, 2016. STUDY SELECTION: English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles, then extracted data from fair- and good-quality trials. Random-effects meta-analysis was used to estimate the benefits of lifestyle-based programs and metformin. MAIN OUTCOMES AND MEASURES: Weight or excess weight (eg, body mass index BMI; BMI z score, measuring the number of standard deviations from the median BMI for age and sex), cardiometabolic outcomes, quality of life, other health outcomes, harms. RESULTS: There was no direct evidence on the benefits or harms of screening children and adolescents for excess weight. Among 42 trials of lifestyle-based interventions to reduce excess weight (N = 6956), those with an estimated 26 hours or more of contact consistently demonstrated mean reductions in excess weight compared with usual care or other control groups after 6 to 12 months, with no evidence of causing harm. Generally, intervention groups showed absolute reductions in BMI z score of 0.20 or more and maintained their baseline weight within a mean of approximately 5 lb, while control groups showed small increases or no change in BMI z score, typically gaining a mean of 5 to 17 lb. Only 3 of 26 interventions with fewer contact hours showed a benefit in weight reduction. Use of metformin (8 studies, n = 616) and orlistat (3 studies, n = 779) were associated with greater BMI reductions compared with placebo: −0.86 (95% CI, −1.44 to −0.29; 6 studies; I2 = 0%) for metformin and −0.50 to −0.94 for orlistat. Groups receiving lifestyle-based interventions offering 52 or more hours of contact showed greater improvements in blood pressure than control groups: −6.4 mm Hg (95% CI, −8.6 to −4.2; 6 studies; I2 = 51%) for systolic blood pressure and −4.0 mm Hg (95% CI, −5.6 to −2.5; 6 studies; I2 = 17%) for diastolic blood pressure. There were mixed findings for insulin or glucose measures and no benefit for lipids. Medications showed small or no benefit for cardiometabolic outcomes, including fasting glucose level. Nonserious harms were common with medication use, although discontinuation due to adverse effects was usually less than 5%. CONCLUSIONS AND RELEVANCE: Lifestyle-based weight loss interventions with 26 or more hours of intervention contact are likely to help reduce excess weight in children and adolescents. The clinical significance of the small benefit of medication use is unclear.
IMPORTANCE: Cardiovascular disease and cancer are the 2 leading causes of death in the US, and vitamin and mineral supplementation has been proposed to help prevent these conditions. OBJECTIVE: To ...review the benefits and harms of vitamin and mineral supplementation in healthy adults to prevent cardiovascular disease and cancer to inform the US Preventive Services Task Force. DATA SOURCES: MEDLINE, PubMed (publisher-supplied records only), Cochrane Library, and Embase (January 2013 to February 1, 2022); prior reviews. STUDY SELECTION: English-language randomized clinical trials (RCTs) of vitamin or mineral use among adults without cardiovascular disease or cancer and with no known vitamin or mineral deficiencies; observational cohort studies examining serious harms. DATA EXTRACTION AND SYNTHESIS: Single extraction, verified by a second reviewer. Quantitative pooling methods appropriate for rare events were used for most analyses. MAIN OUTCOMES AND MEASURES: Mortality, cardiovascular disease events, cancer incidence, serious harms. RESULTS: Eighty-four studies (N=739 803) were included. In pooled analyses, multivitamin use was significantly associated with a lower incidence of any cancer (odds ratio OR, 0.93 95% CI, 0.87-0.99; 4 RCTs n=48 859; absolute risk difference ARD range among adequately powered trials, −0.2% to −1.2%) and lung cancer (OR, 0.75 95% CI, 0.58-0.95; 2 RCTs n=36 052; ARD, 0.2%). However, the evidence for multivitamins had important limitations. Beta carotene (with or without vitamin A) was significantly associated with an increased risk of lung cancer (OR, 1.20 95% CI, 1.01-1.42; 4 RCTs n=94 830; ARD range, −0.1% to 0.6%) and cardiovascular mortality (OR, 1.10 95% CI, 1.02-1.19; 5 RCTs n=94 506 ARD range, −0.8% to 0.8%). Vitamin D use was not significantly associated with all-cause mortality (OR, 0.96 95% CI, 0.91-1.02; 27 RCTs n=117 082), cardiovascular disease (eg, composite cardiovascular disease event outcome: OR, 1.00 95% CI, 0.95-1.05; 7 RCTs n=74 925), or cancer outcomes (eg, any cancer incidence: OR, 0.98 95% CI, 0.92-1.03; 19 RCTs n=86 899). Vitamin E was not significantly associated with all-cause mortality (OR, 1.02 95% CI, 0.97-1.07; 9 RCTs n=107 772), cardiovascular disease events (OR, 0.96 95% CI, 0.90-1.04; 4 RCTs n=62 136), or cancer incidence (OR, 1.02 95% CI, 0.98-1.08; 5 RCTs n=76 777). Evidence for benefit of other supplements was equivocal, minimal, or absent. Limited evidence suggested some supplements may be associated with higher risk of serious harms (hip fracture vitamin A, hemorrhagic stroke vitamin E, and kidney stones vitamin C, calcium). CONCLUSIONS AND RELEVANCE: Vitamin and mineral supplementation was associated with little or no benefit in preventing cancer, cardiovascular disease, and death, with the exception of a small benefit for cancer incidence with multivitamin use. Beta carotene was associated with an increased risk of lung cancer and other harmful outcomes in persons at high risk of lung cancer.
Elevated blood pressure (BP) is the largest contributing risk factor to all-cause and cardiovascular mortality.
To update a systematic review on the benefits and harms of screening for high BP in ...adults and to summarize evidence on rescreening intervals and diagnostic and predictive accuracy of different BP methods for cardiovascular events.
Selected databases searched through 24 February 2014.
Fair- and good-quality trials and diagnostic accuracy and cohort studies conducted in adults and published in English.
One investigator abstracted data, and a second checked for accuracy. Study quality was dual-reviewed.
Ambulatory BP monitoring (ABPM) predicted long-term cardiovascular outcomes independently of office BP (hazard ratio range, 1.28 to 1.40, in 11 studies). Across 27 studies, 35% to 95% of persons with an elevated BP at screening remained hypertensive after nonoffice confirmatory testing. Cardiovascular outcomes in persons who were normotensive after confirmatory testing (isolated clinic hypertension) were similar to outcomes in those who were normotensive at screening. In 40 studies, hypertension incidence after rescreening varied considerably at each yearly interval up to 6 years. Intrastudy comparisons showed at least 2-fold higher incidence in older adults, those with high-normal BP, overweight and obese persons, and African Americans.
Few diagnostic accuracy studies of office BP methods and protocols in untreated adults.
Evidence supports ABPM as the reference standard for confirming elevated office BP screening results to avoid misdiagnosis and overtreatment of persons with isolated clinic hypertension. Persons with BP in the high-normal range, older persons, those with an above-normal body mass index, and African Americans are at higher risk for hypertension on rescreening within 6 years than are persons without these risk factors.
Agency for Healthcare Research and Quality.
Cardiovascular disease (CVD) is the leading cause of death in the United States.
To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in ...adults aged 40 years or older and to evaluate effect modification in subpopulations.
MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews.
Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events.
Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second.
Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk RR, 0.78 95% CI, 0.71 to 0.87) but not nonfatal stroke; aspirin showed little or no benefit for all-cause or cardiovascular mortality. Benefits began within the first 5 years. Older adults achieved greater relative MI reduction, but no other effect modifications were found in analyzed subpopulations. In trials with aspirin doses of 100 mg or less per day, the reduction in nonfatal MI benefit persisted (absolute risk reduction, 0.15 to 1.43 events per 1000 person-years) and a 14% reduction in nonfatal stroke benefit was noted, but no benefit was found for all-cause mortality (RR, 0.95 CI, 0.89 to 1.01) or cardiovascular mortality (RR, 0.97 CI, 0.85 to 1.10).
Evidence for aspirin in primary prevention is heterogeneous and limited by rare events and few credible subgroup analyses.
The beneficial effect of aspirin for the primary prevention of CVD is modest and occurs at doses of 100 mg or less per day. Older adults seem to achieve a greater relative MI benefit.
Agency for Healthcare Research and Quality.
The balance between potential aspirin-related risks and benefits is critical in primary prevention.
To evaluate the risk for serious bleeding with regular aspirin use in cardiovascular disease (CVD) ...primary prevention.
PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (2010 through 6 January 2015), and relevant references from other reviews.
Randomized, controlled trials; cohort studies; and meta-analyses comparing aspirin with placebo or no treatment to prevent CVD or cancer in adults.
One investigator abstracted data, another checked for accuracy, and 2 assessed study quality.
In CVD primary prevention studies, very-low-dose aspirin use (≤100 mg daily or every other day) increased major gastrointestinal (GI) bleeding risk by 58% (odds ratio OR, 1.58 95% CI, 1.29 to 1.95) and hemorrhagic stroke risk by 27% (OR, 1.27 CI, 0.96 to 1.68). Projected excess bleeding events with aspirin depend on baseline assumptions. Estimated excess major bleeding events were 1.39 (CI, 0.70 to 2.28) for GI bleeding and 0.32 (CI, -0.05 to 0.82) for hemorrhagic stroke per 1000 person-years of aspirin exposure using baseline bleeding rates from a community-based observational sample. Such events could be greater among older persons, men, and those with CVD risk factors that also increase bleeding risk.
Power to detect effects on hemorrhagic stroke was limited. Harms other than serious bleeding were not examined.
Consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient.
Agency for Healthcare Research and Quality.
IMPORTANCE: Cardiovascular disease is the leading cause of death in the US, and poor diet and lack of physical activity are major factors contributing to cardiovascular morbidity and mortality. ...OBJECTIVE: To review the benefits and harms of behavioral counseling interventions to improve diet and physical activity in adults with cardiovascular risk factors. DATA SOURCES: MEDLINE, PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials through September 2019; literature surveillance through July 24, 2020. STUDY SELECTION: English-language randomized clinical trials (RCTs) of behavioral counseling interventions to help people with elevated blood pressure or lipid levels improve their diet and increase physical activity. DATA EXTRACTION AND SYNTHESIS: Data were extracted from studies by one reviewer and checked by a second. Random-effects meta-analysis and qualitative synthesis were used. MAIN OUTCOMES AND MEASURES: Cardiovascular events, mortality, subjective well-being, cardiovascular risk factors, diet and physical activity measures (eg, minutes of physical activity, meeting physical activity recommendations), and harms. Interventions were categorized according to estimated contact time as low (≤30 minutes), medium (31-360 minutes), and high (>360 minutes). RESULTS: Ninety-four RCTs were included (N = 52 174). Behavioral counseling interventions involved a median of 6 contact hours and 12 sessions over the course of 12 months and varied in format and dietary recommendations; only 5% addressed physical activity alone. Interventions were associated with a lower risk of cardiovascular events (pooled relative risk, 0.80 95% CI, 0.73-0.87; 9 RCTs n = 12 551; I2 = 0%). Event rates were variable; in the largest trial (Prevención con Dieta Mediterránea PREDIMED), 3.6% in the intervention groups experienced a cardiovascular event, compared with 4.4% in the control group. Behavioral counseling interventions were associated with small, statistically significant reductions in continuous measures of blood pressure, low-density lipoprotein cholesterol levels, fasting glucose levels, and adiposity at 12 to 24 months’ follow-up. Measurement of diet and physical activity was heterogeneous, and evidence suggested small improvements in diet consistent with the intervention recommendation targets but mixed findings and a more limited evidence base for physical activity. Adverse events were rare, with generally no group differences in serious adverse events, any adverse events, hospitalizations, musculoskeletal injuries, or withdrawals due to adverse events. CONCLUSIONS AND RELEVANCE: Medium- and high-contact multisession behavioral counseling interventions to improve diet and increase physical activity for people with elevated blood pressure and lipid levels were effective in reducing cardiovascular events, blood pressure, low-density lipoproteins, and adiposity-related outcomes, with little to no risk of serious harm.
IMPORTANCE: Hypertension is a major risk factor for cardiovascular disease and can be modified through lifestyle and pharmacological interventions to reduce cardiovascular events and mortality. ...OBJECTIVE: To systematically review the benefits and harms of screening and confirmatory blood pressure measurements in adults, to inform the US Preventive Services Task Force. DATA SOURCES: MEDLINE, PubMed, Cochrane Collaboration Central Registry of Controlled Trials, and CINAHL; surveillance through March 26, 2021. STUDY SELECTION: Randomized clinical trials (RCTs) and nonrandomized controlled intervention studies for effectiveness of screening; accuracy studies for screening and confirmatory measurements (ambulatory blood pressure monitoring as the reference standard); RCTs and nonrandomized controlled intervention studies and observational studies for harms of screening and confirmation. DATA EXTRACTION AND SYNTHESIS: Independent critical appraisal and data abstraction; meta-analyses and qualitative syntheses. MAIN OUTCOMES AND MEASURES: Mortality; cardiovascular events; quality of life; sensitivity, specificity, positive and negative predictive values; harms of screening. RESULTS: A total of 52 studies (N = 215 534) were identified in this systematic review. One cluster RCT (n = 140 642) of a multicomponent intervention including hypertension screening reported fewer annual cardiovascular-related hospital admissions for cardiovascular disease in the intervention group compared with the control group (difference, 3.02 per 1000 people; rate ratio, 0.91 95% CI, 0.86-0.97). Meta-analysis of 15 studies (n = 11 309) of initial office-based blood pressure screening showed a pooled sensitivity of 0.54 (95% CI, 0.37-0.70) and specificity of 0.90 (95% CI, 0.84-0.95), with considerable clinical and statistical heterogeneity. Eighteen studies (n = 57 128) of various confirmatory blood pressure measurement modalities were heterogeneous. Meta-analysis of 8 office-based confirmation studies (n = 53 183) showed a pooled sensitivity of 0.80 (95% CI, 0.68-0.88) and specificity of 0.55 (95% CI, 0.42-0.66). Meta-analysis of 4 home-based confirmation studies (n = 1001) showed a pooled sensitivity of 0.84 (95% CI, 0.76-0.90) and a specificity of 0.60 (95% CI, 0.48-0.71). Thirteen studies (n = 5150) suggested that screening was associated with no decrement in quality of life or psychological distress; evidence on absenteeism was mixed. Ambulatory blood pressure measurement was associated with temporary sleep disturbance and bruising. CONCLUSIONS AND RELEVANCE: Screening using office-based blood pressure measurement had major accuracy limitations, including misdiagnosis; however, direct harms of measurement were minimal. Research is needed to determine optimal screening and confirmatory algorithms for clinical practice.
IMPORTANCE: Lipid screening in childhood and adolescence can lead to early dyslipidemia diagnosis. The long-term benefits of lipid screening and subsequent treatment in this population are uncertain. ...OBJECTIVE: To review benefits and harms of screening and treatment of pediatric dyslipidemia due to familial hypercholesterolemia (FH) and multifactorial dyslipidemia. DATA SOURCES: MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022; literature surveillance through March 24, 2023. STUDY SELECTION: English-language randomized clinical trials (RCTs) of lipid screening; recent, large US cohort studies reporting diagnostic yield or screen positivity; and RCTs of lipid-lowering interventions. DATA EXTRACTION AND SYNTHESIS: Single extraction, verified by a second reviewer. Quantitative synthesis using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Health outcomes, diagnostic yield, intermediate outcomes, behavioral outcomes, and harms. RESULTS: Forty-three studies were included (n = 491 516). No RCTs directly addressed screening effectiveness and harms. Three US studies (n = 395 465) reported prevalence of phenotypically defined FH of 0.2% to 0.4% (1:250 to 1:500). Five studies (n = 142 257) reported multifactorial dyslipidemia prevalence; the prevalence of elevated total cholesterol level (≥200 mg/dL) was 7.1% to 9.4% and of any lipid abnormality was 19.2%. Ten RCTs in children and adolescents with FH (n = 1230) demonstrated that statins were associated with an 81- to 82-mg/dL greater mean reduction in levels of total cholesterol and LDL-C compared with placebo at up to 2 years. Nonstatin-drug trials showed statistically significant lowering of lipid levels in FH populations, but few studies were available for any single drug. Observational studies suggest that statin treatment for FH starting in childhood or adolescence reduces long-term cardiovascular disease risk. Two multifactorial dyslipidemia behavioral counseling trials (n = 934) demonstrated 3- to 6-mg/dL greater reductions in total cholesterol levels compared with the control group, but findings did not persist at longest follow-up. Harms reported in the short-term drug trials were similar in the intervention and control groups. CONCLUSIONS AND RELEVANCE: No direct evidence on the benefits or harms of pediatric lipid screening was identified. While multifactorial dyslipidemia is common, no evidence was found that treatment is effective for this condition. In contrast, FH is relatively rare; evidence shows that statins reduce lipid levels in children with FH, and observational studies suggest that such treatment has long-term benefit for this condition.
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