Chris Kypridemos

Modeling Future Cardiovascular Disease Mortality in the United States National Trends and Racial and Ethnic Disparities

Background— Accurate forecasting of cardiovascular disease mortality is crucial to guide policy and programming efforts. Prior forecasts often have not incorporated past trends in rates of reduction in cardiovascular disease mortality. This creates uncertainties about future trends in cardiovascular disease mortality and disparities. Methods and Results— To forecast US cardiovascular disease mortality and disparities to 2030, we developed a hierarchical bayesian model to determine and incorporate prior age, period, and cohort effects from 1979 to 2012, stratified by age, sex, and race, which we combined with expected demographic shifts to 2030. Data sources included the National Vital Statistics System, Surveillance, Epidemiology, and End Results (SEER) single-year population estimates, and US Bureau of Statistics 2012 national population projections. We projected coronary disease and stroke deaths to 2030, first on the basis of constant age, period, and cohort effects at 2012 values, as is most commonly done (conventional), and then with the use of more rigorous projections incorporating expected trends in age, period, and cohort effects (trend based). We primarily evaluated absolute mortality. The conventional model projected total coronary and stroke deaths by 2030 to increase by ≈18% (67 000 additional coronary deaths per year) and 50% (64 000 additional stroke deaths per year). Conversely, the trend-based model projected that coronary mortality would decrease by 2030 by ≈27% (79 000 fewer deaths per year) and stroke mortality would remain unchanged (200 fewer deaths per year). Health disparities will be improved in stroke deaths but not coronary deaths. Conclusions— After prior mortality trends and expected demographic shifts are accounted for, total US coronary deaths are expected to decline, whereas stroke mortality will remain relatively constant. Health disparities in stroke but not coronary deaths will be improved but not eliminated. These age, period, and cohort approaches offer more plausible predictions than conventional estimates.Background— Accurate forecasting of cardiovascular disease mortality is crucial to guide policy and programming efforts. Prior forecasts often have not incorporated past trends in rates of reduction in cardiovascular disease mortality. This creates uncertainties about future trends in cardiovascular disease mortality and disparities. Methods and Results— To forecast US cardiovascular disease mortality and disparities to 2030, we developed a hierarchical bayesian model to determine and incorporate prior age, period, and cohort effects from 1979 to 2012, stratified by age, sex, and race, which we combined with expected demographic shifts to 2030. Data sources included the National Vital Statistics System, Surveillance, Epidemiology, and End Results (SEER) single-year population estimates, and US Bureau of Statistics 2012 national population projections. We projected coronary disease and stroke deaths to 2030, first on the basis of constant age, period, and cohort effects at 2012 values, as is most commonly done (conventional), and then with the use of more rigorous projections incorporating expected trends in age, period, and cohort effects (trend based). We primarily evaluated absolute mortality. The conventional model projected total coronary and stroke deaths by 2030 to increase by ≈18% (67 000 additional coronary deaths per year) and 50% (64 000 additional stroke deaths per year). Conversely, the trend-based model projected that coronary mortality would decrease by 2030 by ≈27% (79 000 fewer deaths per year) and stroke mortality would remain unchanged (200 fewer deaths per year). Health disparities will be improved in stroke deaths but not coronary deaths. Conclusions— After prior mortality trends and expected demographic shifts are accounted for, total US coronary deaths are expected to decline, whereas stroke mortality will remain relatively constant. Health disparities in stroke but not coronary deaths will be improved but not eliminated. These age, period, and cohort approaches offer more plausible predictions than conventional estimates. # CLINICAL PERSPECTIVE {#article-title-31}

Cardiovascular screening to reduce the burden from cardiovascular disease: microsimulation study to quantify policy options

Objectives To estimate the potential impact of universal screening for primary prevention of cardiovascular disease (National Health Service Health Checks) on disease burden and socioeconomic inequalities in health in England, and to compare universal screening with alternative feasible strategies. Design Microsimulation study of a close-to-reality synthetic population. Five scenarios were considered: baseline scenario, assuming that current trends in risk factors will continue in the future; universal screening; screening concentrated only in the most deprived areas; structural population-wide intervention; and combination of population-wide intervention and concentrated screening. Setting Synthetic population with similar characteristics to the community dwelling population of England. Participants Synthetic people with traits informed by the health survey for England. Main outcome measure Cardiovascular disease cases and deaths prevented or postponed by 2030, stratified by fifths of socioeconomic status using the index of multiple deprivation. Results Compared with the baseline scenario, universal screening may prevent or postpone approximately 19 000 cases (interquartile range 11 000-28 000) and 3000 deaths (−1000-6000); concentrated screening 17 000 cases (9000-26 000) and 2000 deaths (−1000-5000); population-wide intervention 67 000 cases (57 000-77 000) and 8000 deaths (4000-11 000); and the combination of the population-wide intervention and concentrated screening 82 000 cases (73 000-93 000) and 9000 deaths (6000-13 000). The most equitable strategy would be the combination of the population-wide intervention and concentrated screening, followed by concentrated screening alone and the population-wide intervention. Universal screening had the least apparent impact on socioeconomic inequalities in health. Conclusions When primary prevention strategies for reducing cardiovascular disease burden and inequalities are compared, universal screening seems less effective than alternative strategies, which incorporate population-wide approaches. Further research is needed to identify the best mix of population-wide and risk targeted CVD strategies to maximise cost effectiveness and minimise inequalities.

Systematic review of dietary salt reduction policies: Evidence for an effectiveness hierarchy?

Background Non-communicable disease (NCD) prevention strategies now prioritise four major risk factors: food, tobacco, alcohol and physical activity. Dietary salt intake remains much higher than recommended, increasing blood pressure, cardiovascular disease and stomach cancer. Substantial reductions in salt intake are therefore urgently needed. However, the debate continues about the most effective approaches. To inform future prevention programmes, we systematically reviewed the evidence on the effectiveness of possible salt reduction interventions. We further compared “downstream, agentic” approaches targeting individuals with “upstream, structural” policy-based population strategies. Methods We searched six electronic databases (CDSR, CRD, MEDLINE, SCI, SCOPUS and the Campbell Library) using a pre-piloted search strategy focussing on the effectiveness of population interventions to reduce salt intake. Retrieved papers were independently screened, appraised and graded for quality by two researchers. To facilitate comparisons between the interventions, the extracted data were categorised using nine stages along the agentic/structural continuum, from “downstream”: dietary counselling (for individuals, worksites or communities), through media campaigns, nutrition labelling, voluntary and mandatory reformulation, to the most “upstream” regulatory and fiscal interventions, and comprehensive strategies involving multiple components. Results After screening 2,526 candidate papers, 70 were included in this systematic review (49 empirical studies and 21 modelling studies). Some papers described several interventions. Quality was variable. Multi-component strategies involving both upstream and downstream interventions, generally achieved the biggest reductions in salt consumption across an entire population, most notably 4g/day in Finland and Japan, 3g/day in Turkey and 1.3g/day recently in the UK. Mandatory reformulation alone could achieve a reduction of approximately 1.45g/day (three separate studies), followed by voluntary reformulation (-0.8g/day), school interventions (-0.7g/day), short term dietary advice (-0.6g/day) and nutrition labelling (-0.4g/day), but each with a wide range. Tax and community based counselling could, each typically reduce salt intake by 0.3g/day, whilst even smaller population benefits were derived from health education media campaigns (-0.1g/day). Worksite interventions achieved an increase in intake (+0.5g/day), however, with a very wide range. Long term dietary advice could achieve a -2g/day reduction under optimal research trial conditions; however, smaller reductions might be anticipated in unselected individuals. Conclusions Comprehensive strategies involving multiple components (reformulation, food labelling and media campaigns) and “upstream” population-wide policies such as mandatory reformulation generally appear to achieve larger reductions in population-wide salt consumption than “downstream”, individually focussed interventions. This ‘effectiveness hierarchy’ might deserve greater emphasis in future NCD prevention strategies.

Fruit and vegetable consumption and non-communicable disease: time to update the ‘5 a day’ message?

Studies reporting ‘new’ associations of food ingredients with diseases are common, and sensational headlines appear almost daily in the news media. Thus, in a recent provocative paper, Schoenfeld and Ioannidis,1 randomly selected 50 common ingredients from a cookbook, and reported that 40 were apparently associated with increased cancer risk in peer reviewed studies. Unsurprisingly, most of these associations disappeared in subsequent meta-analyses.1 The net result: increases in media profits, public anxiety and a number of confused politicians. Indeed, the current landscape in nutritional epidemiology research is blighted by an oversaturation of contradictory evidence which risks confusing policy makers, journalists and public about what aspects of the Western diet deserve attention and then intervention. Randomised controlled trails and meta-analyses offer an evidence ‘gold standard’ relatively free of biases. However, trials are simply not feasible, affordable or ethical for many of the most important dietary questions. We therefore fall back on analyses of long-term cohorts, at which point considerable cautions then need to be sounded. Thus, the populations under study may be highly selected (eg, US doctors or nurses), and the results may not be directly generalisable to the …

Estimated reductions in cardiovascular and gastric cancer disease burden through salt policies in England: An IMPACT NCD microsimulation study

Objective To estimate the impact and equity of existing and potential UK salt reduction policies on primary prevention of cardiovascular disease (CVD) and gastric cancer (GCa) in England. Design A microsimulation study of a close-to-reality synthetic population. In the first period, 2003–2015, we compared the impact of current policy against a counterfactual ‘no intervention’ scenario, which assumed salt consumption persisted at 2003 levels. For 2016–2030, we assumed additional legislative policies could achieve a steeper salt decline and we compared this against the counterfactual scenario that the downward trend in salt consumption observed between 2001 and 2011 would continue up to 2030. Setting Synthetic population with similar characteristics to the non-institutionalised population of England. Participants Synthetic individuals with traits informed by the Health Survey for England. Main measure CVD and GCa cases and deaths prevented or postponed, stratified by fifths of socioeconomic status using the Index of Multiple Deprivation. Results Since 2003, current salt policies have prevented or postponed ∼52 000 CVD cases (IQR: 34 000–76 000) and 10 000 CVD deaths (IQR: 3000–17 000). In addition, the current policies have prevented ∼5000 new cases of GCa (IQR: 2000–7000) resulting in about 2000 fewer deaths (IQR: 0–4000). This policy did not reduce socioeconomic inequalities in CVD, and likely increased inequalities in GCa. Additional legislative policies from 2016 could further prevent or postpone ∼19 000 CVD cases (IQR: 8000–30 000) and 3600 deaths by 2030 (IQR: −400–8100) and may reduce inequalities. Similarly for GCa, 1200 cases (IQR: −200–3000) and 700 deaths (IQR: −900–2300) could be prevented or postponed with a neutral impact on inequalities. Conclusions Current salt reduction policies are powerfully effective in reducing the CVD and GCa burdens overall but fail to reduce the inequalities involved. Additional structural policies could achieve further, more equitable health benefits.

A victory for statins or a defeat for diet policies? Cholesterol falls in Poland in the past decade: A modeling study ☆

AIM The present study is aimed to examine whether recent changes in population total cholesterol (TC) levels in Poland might be attributed to increased use statins. METHODS Two independent, nationally representative cross-sectional studies were conducted in adults aged 18-79 years in 2002 (n=2993, mean age 46.2 years) and 2011 (n=2413, mean age 45.8 years), including measurements of TC in venous blood samples. The mean change of TC between 2002 and 2011 was assessed. Then the expected therapeutic reduction in TC level in 2011 attributable to statins only was calculated based on already published statin effectiveness data. Uncertainty was quantified using probabilistic sensitivity analysis. RESULTS Statin uptake in Poland rose to 11.2% in 2011 (95% Confidence Intervals (CI): 10% to 12.5%) and approximately 32% (95% CI: 28.4 to 36.0%) in subjects aged 60-79 years. Mean TC in Poland in 2002 was 5.35 mmol/l, and fell by 0.21 mmol/l (95% CI: 0.14 to 0.28) by 2011. This fall would have been only 0.03 mmol/l (95% CI: -0.04 to 0.10) for the total adult population and 0.06 mmol/l (95% CI: -0.09 to 0.22) in people aged 60-79 years if statins had not been used. Statin use thus apparently explained approximately 85% (95% CI: 49% to 120%) of the observed decrease. CONCLUSION Between 2002 and 2011, statin medications apparently explained a large part of the observed fall in population cholesterol level, suggesting very little changes in population TC attributed to dietary changes.

Modelling Future Cardiovascular Disease Mortality in the United States: National Trends and Racial and Ethnic Disparities

Background— Accurate forecasting of cardiovascular disease mortality is crucial to guide policy and programming efforts. Prior forecasts often have not incorporated past trends in rates of reduction in cardiovascular disease mortality. This creates uncertainties about future trends in cardiovascular disease mortality and disparities. Methods and Results— To forecast US cardiovascular disease mortality and disparities to 2030, we developed a hierarchical bayesian model to determine and incorporate prior age, period, and cohort effects from 1979 to 2012, stratified by age, sex, and race, which we combined with expected demographic shifts to 2030. Data sources included the National Vital Statistics System, Surveillance, Epidemiology, and End Results (SEER) single-year population estimates, and US Bureau of Statistics 2012 national population projections. We projected coronary disease and stroke deaths to 2030, first on the basis of constant age, period, and cohort effects at 2012 values, as is most commonly done (conventional), and then with the use of more rigorous projections incorporating expected trends in age, period, and cohort effects (trend based). We primarily evaluated absolute mortality. The conventional model projected total coronary and stroke deaths by 2030 to increase by ≈18% (67 000 additional coronary deaths per year) and 50% (64 000 additional stroke deaths per year). Conversely, the trend-based model projected that coronary mortality would decrease by 2030 by ≈27% (79 000 fewer deaths per year) and stroke mortality would remain unchanged (200 fewer deaths per year). Health disparities will be improved in stroke deaths but not coronary deaths. Conclusions— After prior mortality trends and expected demographic shifts are accounted for, total US coronary deaths are expected to decline, whereas stroke mortality will remain relatively constant. Health disparities in stroke but not coronary deaths will be improved but not eliminated. These age, period, and cohort approaches offer more plausible predictions than conventional estimates.Background— Accurate forecasting of cardiovascular disease mortality is crucial to guide policy and programming efforts. Prior forecasts often have not incorporated past trends in rates of reduction in cardiovascular disease mortality. This creates uncertainties about future trends in cardiovascular disease mortality and disparities. Methods and Results— To forecast US cardiovascular disease mortality and disparities to 2030, we developed a hierarchical bayesian model to determine and incorporate prior age, period, and cohort effects from 1979 to 2012, stratified by age, sex, and race, which we combined with expected demographic shifts to 2030. Data sources included the National Vital Statistics System, Surveillance, Epidemiology, and End Results (SEER) single-year population estimates, and US Bureau of Statistics 2012 national population projections. We projected coronary disease and stroke deaths to 2030, first on the basis of constant age, period, and cohort effects at 2012 values, as is most commonly done (conventional), and then with the use of more rigorous projections incorporating expected trends in age, period, and cohort effects (trend based). We primarily evaluated absolute mortality. The conventional model projected total coronary and stroke deaths by 2030 to increase by ≈18% (67 000 additional coronary deaths per year) and 50% (64 000 additional stroke deaths per year). Conversely, the trend-based model projected that coronary mortality would decrease by 2030 by ≈27% (79 000 fewer deaths per year) and stroke mortality would remain unchanged (200 fewer deaths per year). Health disparities will be improved in stroke deaths but not coronary deaths. Conclusions— After prior mortality trends and expected demographic shifts are accounted for, total US coronary deaths are expected to decline, whereas stroke mortality will remain relatively constant. Health disparities in stroke but not coronary deaths will be improved but not eliminated. These age, period, and cohort approaches offer more plausible predictions than conventional estimates. # CLINICAL PERSPECTIVE {#article-title-31}

Quantifying the Contribution of Statins to the Decline in Population Mean Cholesterol by Socioeconomic Group in England 1991 - 2012: A Modelling Study

Background Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statins are effective for cholesterol control in individual patients. At the population level, however, their contribution to total cholesterol decline remains unclear. The aim of this study was to quantify the contribution of statins to the observed fall in population mean cholesterol levels in England over the past two decades, and explore any differences between socioeconomic groups. Methods and Findings This is a modelling study based on data from the Health Survey for England. We analysed changes in observed mean total cholesterol levels in the adult England population between 1991-92 (baseline) and 2011-12. We then compared the observed changes with a counterfactual ‘no statins’ scenario, where the impact of statins on population total cholesterol was estimated and removed. We estimated uncertainty intervals (UI) using Monte Carlo simulation, where confidence intervals (CI) were impractical. In 2011-12, 13.2% (95% CI: 12.5-14.0%) of the English adult population used statins at least once per week, compared with 1991-92 when the proportion was just 0.5% (95% CI: 0.3-1.0%). Between 1991-92 and 2011-12, mean total cholesterol declined from 5.86 mmol/L (95% CI: 5.82-5.90) to 5.17 mmol/L (95% CI: 5.14-5.20). For 2011-12, mean total cholesterol was lower in more deprived groups. In our ‘no statins’ scenario we predicted a mean total cholesterol of 5.36 mmol/L (95% CI: 5.33-5.40) for 2011-12. Statins were responsible for approximately 33.7% (95% UI: 28.9-38.8%) of the total cholesterol reduction since 1991-92. The statin contribution to cholesterol reduction was greater among the more deprived groups of women, while showing little socio-economic gradient among men. Conclusions Our model suggests that statins explained around a third of the substantial falls in total cholesterol observed in England since 1991. Approximately two thirds of the cholesterol decrease can reasonably be attributed non-pharmacological determinants.

Systematic review of dietary trans-fat reduction interventions

Abstract Objective To systematically review published studies of interventions to reduce people’s intake of dietary trans-fatty acids (TFAs). Methods We searched online databases (CINAHL, the CRD Wider Public Health database, Cochrane Database of Systematic Reviews, Ovid®, MEDLINE®, Science Citation Index and Scopus) for studies evaluating TFA interventions between 1986 and 2017. Absolute decrease in TFA consumption (g/day) was the main outcome measure. We excluded studies reporting only on the TFA content in food products without a link to intake. We included trials, observational studies, meta-analyses and modelling studies. We conducted a narrative synthesis to interpret the data, grouping studies on a continuum ranging from interventions targeting individuals to population-wide, structural changes. Results After screening 1084 candidate papers, we included 23 papers: 12 empirical and 11 modelling studies. Multiple interventions in Denmark achieved a reduction in TFA consumption from 4.5 g/day in 1976 to 1.5 g/day in 1995 and then virtual elimination after legislation banning TFAs in manufactured food in 2004. Elsewhere, regulations mandating reformulation of food reduced TFA content by about 2.4 g/day. Worksite interventions achieved reductions averaging 1.2 g/day. Food labelling and individual dietary counselling both showed reductions of around 0.8 g/day. Conclusion Multicomponent interventions including legislation to eliminate TFAs from food products were the most effective strategy. Reformulation of food products and other multicomponent interventions also achieved useful reductions in TFA intake. By contrast, interventions targeted at individuals consistently achieved smaller reductions. Future prevention strategies should consider this effectiveness hierarchy to achieve the largest reductions in TFA consumption.

Estimating the health and economic effects of the proposed US Food and Drug Administration voluntary sodium reformulation: Microsimulation cost-effectiveness analysis

Background Sodium consumption is a modifiable risk factor for higher blood pressure (BP) and cardiovascular disease (CVD). The US Food and Drug Administration (FDA) has proposed voluntary sodium reduction goals targeting processed and commercially prepared foods. We aimed to quantify the potential health and economic impact of this policy. Methods and findings We used a microsimulation approach of a close-to-reality synthetic population (US IMPACT Food Policy Model) to estimate CVD deaths and cases prevented or postponed, quality-adjusted life years (QALYs), and cost-effectiveness from 2017 to 2036 of 3 scenarios: (1) optimal, 100% compliance with 10-year reformulation targets; (2) modest, 50% compliance with 10-year reformulation targets; and (3) pessimistic, 100% compliance with 2-year reformulation targets, but with no further progress. We used the National Health and Nutrition Examination Survey and high-quality meta-analyses to inform model inputs. Costs included government costs to administer and monitor the policy, industry reformulation costs, and CVD-related healthcare, productivity, and informal care costs. Between 2017 and 2036, the optimal reformulation scenario achieving the FDA sodium reduction targets could prevent approximately 450,000 CVD cases (95% uncertainty interval: 240,000 to 740,000), gain approximately 2.1 million discounted QALYs (1.7 million to 2.4 million), and produce discounted cost savings (health savings minus policy costs) of approximately