Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial.

Importance: Previous randomized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence. Objective: To examine whether high-dose vitamin D supplementation received monthly, without calcium, is associated with a reduction in cancer incidence and cancer mortality in the general population. Design, Setting, and Participants: This is a post hoc analysis of data from the Vitamin D Assessment (ViDA) study, a randomized, double-blind, placebo-controlled trial that recruited participants from family practices and community groups in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up completed December 31, 2015. Participants were adult community residents aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants withdrew consent, and all others (n = 5108) were included in the primary analysis. Data analysis was by intention to treat. Interventions: Oral vitamin D3, in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). Main Outcomes and Measures: Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms (excluding nonmelanoma skin cancers) diagnosed from randomization until the study medication was discontinued on July 31, 2015. Results: Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 58.1% were male, and 4253 (83.3%) were of European or another race/ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 (9.0) ng/mL. In a random sample of 438 participants, the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of cancer comprised 328 total cases of cancer (259 invasive and 69 in situ malignant neoplasms) and occurred in 165 of 2558 participants (6.5%) in the vitamin D group and 163 of 2550 (6.4%) in the placebo group, yielding an adjusted hazard ratio of 1.01 (95% CI, 0.81-1.25; P = .95). Conclusions and Relevance: High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer. This study suggests that daily or weekly dosing for a longer period may require further study. Trial Registration: anzctr.org.au Identifier: ACTRN12611000402943.

Monthly vitamin D supplementation, pain, and pattern of analgesic prescription: secondary analysis from the randomized, double-blind, placebo-controlled Vitamin D Assessment study.

Observational studies suggest that vitamin D deficiency is associated with higher risk of pain. However, evidence on the effect of vitamin D supplementation on pain is limited and contradictory. The aim of this study was to compare the effect of monthly high-dose vitamin D supplementation on a pain impact questionnaire (PIQ-6) score and prescription of analgesics in the general population. We performed a randomized, double-blind, placebo-controlled trial of 5108 community-dwelling participants, aged 50 to 84 years, who were randomly assigned to receive monthly 100,000-IU capsules of vitamin D3 (n = 2558) or placebo (n = 2550) for a median of 3.3 years. The PIQ-6 was administered at baseline, year 1, and final follow-up. Analgesic prescription data were collected from Ministry of Health. There was no difference in mean PIQ-6 score at the end of follow-up (adjusted mean difference: 0.06; P = 0.82) between the vitamin D (n = 2041) and placebo (n = 2014) participants. The proportion of participants dispensed one or more opioids was similar in the vitamin D group (n = 559, 21.9%) compared with placebo (n = 593, 23.3%); the relative risk (RR) adjusted for age, sex, and ethnicity was 0.94 (P = 0.24). Similar results were observed for dispensing of nonsteroidal anti-inflammatory drugs (RR = 0.94; P = 0.24) and other nonopioids (RR = 0.98; P = 0.34). Focusing on vitamin D deficient participants (<50 nmol/L, 24.9%), there was a lower risk of dispensing nonsteroidal anti-inflammatory drugs in the vitamin D group compared with placebo (RR = 0.87; P = 0.009); all other subgroup analyses were not significant. Long-term monthly high-dose vitamin D supplementation did not improve mean PIQ-6 score or reduce analgesic dispensing in the general population.

Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial.

Importance: Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D. Objective: To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population. Design, Setting, and Participants: The Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis. Interventions: Oral vitamin D3 in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). Main Outcomes and Measures: The primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis. Results: Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes. Conclusions and Relevance: Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study. Trial Registration: clinicaltrials.gov Identifier: ACTRN12611000402943.

The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures.

Observational studies have shown that low vitamin D status is associated with an increased risk of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. We recruited 5110 Auckland adults, aged 50-84 years, into a randomized, double-blind, placebo-controlled trial to test whether vitamin D supplementation protects against these four major outcomes. The intervention is a monthly cholecalciferol dose of 100,000IU (2.5mg) for an estimated median 3.3 years (range 2.5-4.2) during 2011-2015. Participants were recruited primarily from family practices, plus community groups with a high proportion of Maori, Pacific, or South Asian individuals. The baseline evaluation included medical history, lifestyle, physical measurements (e.g. blood pressure, arterial waveform, lung function, muscle function), and a blood sample (stored at -80°C for later testing). Capsules are being mailed to home addresses with a questionnaire to collect data on non-hospitalized outcomes and to monitor adherence and potential adverse effects. Other data sources include New Zealand Ministry of Health data on mortality, hospitalization, cancer registrations and dispensed pharmaceuticals. A random sample of 438 participants returned for annual collection of blood samples to monitor adherence and safety (hypercalcemia), including repeat physical measurements at 12 months follow-up. The trial will allow testing of a priori hypotheses on several other endpoints including: weight, blood pressure, arterial waveform parameters, heart rate variability, lung function, muscle strength, gait and balance, mood, psoriasis, bone density, and chronic pain.

The global burden of hemorrhagic stroke: a summary of findings from the GBD 2010 study.

This report summarizes the findings of the GBD 2010 (Global Burden of Diseases, Injuries, and Risk Factors) study for hemorrhagic stroke (HS). Multiple databases were searched for relevant studies published between 1990 and 2010. The GBD 2010 study provided standardized estimates of the incidence, mortality, mortality-to-incidence ratios (MIR), and disability-adjusted life years (DALY) lost for HS (including intracerebral hemorrhage and subarachnoid hemorrhage) by age, sex, and income level (high-income countries [HIC]; low- and middle-income countries [LMIC]) for 21 GBD 2010 regions in 1990, 2005, and 2010. In 2010, there were 5.3 million cases of HS and over 3.0 million deaths due to HS. There was a 47% increase worldwide in the absolute number of HS cases. The largest proportion of HS incident cases (80%) and deaths (63%) occurred in LMIC countries. There were 62.8 million DALY lost (86% in LMIC) due to HS. The overall age-standardized incidence rate of HS per 100,000 person-years in 2010 was 48.41 (95% confidence interval [CI]: 45.44 to 52.13) in HIC and 99.43 (95% CI: 85.37 to 116.28) in LMIC, and 81.52 (95% CI: 72.27 to 92.82) globally. The age-standardized incidence of HS increased by 18.5% worldwide between 1990 and 2010. In HIC, there was a reduction in incidence of HS by 8% (95% CI: 1% to 15%), mortality by 38% (95% CI: 32% to 43%), DALY by 39% (95% CI: 32% to 44%), and MIR by 27% (95% CI: 19% to 35%) in the last 2 decades. In LMIC countries, there was a significant increase in the incidence of HS by 22% (95% CI: 5% to 30%), whereas there was a significant reduction in mortality rates of 23% (95% CI: -3% to 36%), DALY lost of 25% (95% CI: 7% to 38%), and MIR by 36% (95% CI: 16% to 49%). There were significant regional differences in incidence rates of HS, with the highest rates in LMIC regions such as sub-Saharan Africa and East Asia, and lowest rates in High Income North America and Western Europe. The worldwide burden of HS has increased over the last 2 decades in terms of absolute numbers of HS incident events. The majority of the burden of HS is borne by LMIC. Rates for HS incidence, mortality, and DALY lost, as well as MIR decreased in the past 2 decades in HIC, but increased significantly in LMIC countries, particularly in those patients ≤75 years. HS affected people at a younger age in LMIC than in HIC. The lowest incidence and mortality rates in 2010 were in High Income North America, Australasia, and Western Europe, whereas the highest rates were in Central Asia, Southeast Asia, and sub-Saharan Africa. These results suggest that reducing the burden of HS is a priority particularly in LMIC. The GBD 2010 findings may be a useful resource for planning strategies to reduce the global burden of HS.

The global burden of ischemic stroke: findings of the GBD 2010 study.

This study sought to summarize the findings of the GBD 2010 (Global Burden of Diseases, Injuries, and Risk Factors) study for ischemic stroke (IS) and to report the impact of tobacco smoking on IS burden in specific countries. The GBD 2010 searched multiple databases to identify relevant studies published between 1990 and 2010. The GBD 2010 analytical tools were used to calculate region-specific IS incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life years (DALY) lost, including 95% uncertainty intervals (UI). In 2010, there were approximately 11,569,000 incident IS events (63% in low- and middle-income countries [LMIC]), approximately 2,835,000 deaths from IS (57% in LMIC), and approximately 39,389,000 DALY lost due to IS (64% in LMIC). From 1990 to 2010, there was a significant increase in global IS burden in terms of absolute number of people with incident IS (37% increase), deaths from IS (21% increase), and DALY lost due to IS (18% increase). Age-standardized IS incidence, DALY lost, mortality, and mortality-to-incidence ratios in high-income countries declined by about 13% (95% UI: 6% to 18%), 34% (95% UI: 16% to 36%), and 37% (95% UI: 19% to 39%), 21% (95% UI: 10% to 27%), respectively. However, in LMIC there was a modest 6% increase in the age-standardized incidence of IS (95% UI: -7% to 18%) despite modest reductions in mortality rates, DALY lost, and mortality-to-incidence ratios. There was considerable variability among country-specific estimates within broad GBD regions. China, Russia, and India were ranked highest in both 1990 and 2010 for IS deaths attributable to tobacco consumption. Although age-standardized IS mortality rates have declined over the last 2 decades, the absolute global burden of IS is increasing, with the bulk of DALY lost in LMIC. Tobacco consumption is an important modifiable risk factor for IS, and in both 1990 and 2010, the top ranked countries for IS deaths that could be attributed to tobacco consumption were China, Russia, and India. Tobacco control policies that target both smoking initiation and smoking cessation can play an important role in the prevention of IS. In China, Russia, and India, even modest reductions in the number of current smokers could see millions of lives saved due to prevention of IS alone.

Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010.

BACKGROUND: Although stroke is the second leading cause of death worldwide, no comprehensive and comparable assessment of incidence, prevalence, mortality, disability, and epidemiological trends has been estimated for most regions. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990-2010. METHODS: We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and WHO regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010.We applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific, pre-specified associations between incidence, prevalence, and mortality, to calculate regional and country-specific estimates of stroke incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age group (<75 years, ≥ 75 years, and in total)and country income level (high-income, and low-income and middle-income) for 1990, 2005, and 2010. FINDINGS: We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). From 1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12% (95% CI 6-17)in high-income countries, and increased by 12% (-3 to 22) in low-income and middle-income countries, albeit nonsignificantly. Mortality rates decreased significantly in both high income (37%, 31-41) and low-income and middle income countries (20%, 15-30). In 2010, the absolute numbers of people with fi rst stroke (16・9 million), stroke survivors (33 million), stroke-related deaths (5・9 million), and DALYs lost (102 million) were high and had significantly increased since 1990 (68%, 84%, 26%, and 12% increase, respectively), with most of the burden (68・6% incident strokes, 52・2% prevalent strokes, 70・9% stroke deaths, and 77・7% DALYs lost) in low-income and middle-income countries. In 2010, 5・2 million (31%) strokes were in children (aged <20 years old) and young and middle-aged adults(20-64 years), to which children and young and middle-aged adults from low-income and middle-income countries contributed almost 74 000 (89%) and 4・0 million (78%), respectively, of the burden. Additionally, we noted significant geographical differences of between three and ten times in stroke burden between GBD regions and countries. More than 62% of new strokes, 69・8% of prevalent strokes, 45・5% of deaths from stroke, and 71・7% of DALYs lost because of stroke were in people younger than 75 years. INTERPRETATION: Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades,the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels. FUNDING: Bill & Melinda Gates Foundation.

Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010.

BACKGROUND: The burden of ischaemic and haemorrhagic stroke varies between regions and over time. With differences in prognosis, prevalence of risk factors, and treatment strategies, knowledge of stroke pathological type is important for targeted region-specific health-care planning for stroke and could inform priorities for type-specific prevention strategies. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010. METHODS: We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR) to calculate regional and country-specific estimates for ischaemic and haemorrhagic stroke incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life-years (DALYs) lost, by age group (aged <75 years, ≥ 75 years, and in total) and country income level (high-income and low-income and middle-income) for 1990, 2005, and 2010. FINDINGS: We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemic and haemorrhagic stroke (37% and 47% increase, respectively), number of deaths (21% and 20% increase), and DALYs lost (18% and 14% increase). In the past two decades in high-income countries, incidence of ischaemic stroke reduced significantly by 13% (95% CI 6-18), mortality by 37% (19-39), DALYs lost by 34% (16-36), and mortality-to-incidence ratios by 21% (10-27). For haemorrhagic stroke, incidence reduced significantly by 19% (1-15), mortality by 38% (32-43), DALYs lost by 39% (32-44), and mortality-to-incidence ratios by 27% (19-35). By contrast, in low-income and middle-income countries, we noted a significant increase of 22% (5-30) in incidence of haemorrhagic stroke and a 6% (-7 to 18) non-significant increase in the incidence of ischaemic stroke. Mortality rates for ischaemic stroke fell by 14% (9-19), DALYs lost by 17% (-11 to 21%), and mortality-to-incidence ratios by 16% (-12 to 22). For haemorrhagic stroke in low-income and middle-income countries, mortality rates reduced by 23% (-18 to 25%), DALYs lost by 25% (-21 to 28), and mortality-to-incidence ratios by 36% (-34 to 28). INTERPRETATION: Although age-standardised mortality rates for ischaemic and haemorrhagic stroke have decreased in the past two decades, the absolute number of people who have these stroke types annually, and the number with related deaths and DALYs lost, is increasing, with most of the burden in low-income and middle-income countries. Further study is needed in these countries to identify which subgroups of the population are at greatest risk and who could be targeted for preventive efforts.

Estimating energy expenditure with the RT3 triaxial accelerometer.

The RT3 is a relatively new triaxial accelerometer that has replaced the TniTrac. The aim of this study was to validate the RT3 against doubly labeled water (DLW) in a free-living, mixed weight sample of adults. Total energy expenditure (TEE) was measured over a 15-day period using DLW Activity-related energy expenditure (AEE) was estimated by subtracting resting energy expenditure and thermic effect of feeding from TEE. The RT3 triaxial accelerometer was worn over 14 consecutive days. TEE and AEE were estimated using the RT3 proprietary equation. Thirty-six adults ages 18-56 years (56% women) with an average weight of 75.9 kg (SD = 14.8) completed all measurements. Compared to DLW the RT3 underestimated TEE by 539 kJ (4%) and AEE by 485 kJ (15%) on average. The RT3 provided a relatively accurate assessment of free-living activity-related energy expenditure at the group level and generally underestimated total and activity-related energy expenditure compared to DLW

Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review.

This systematic review of population-based studies of the incidence and early (21 days to 1 month) case fatality of stroke is based on studies published from 1970 to 2008. Stroke incidence (incident strokes only) and case fatality from 21 days to 1 month post-stroke were analysed by four decades of study, two country income groups (high-income countries and low to middle income countries, in accordance with the World Bank's country classification) and, when possible, by stroke pathological type: ischaemic stroke, primary intracerebral haemorrhage, and subarachnoid haemorrhage. This Review shows a divergent, statistically significant trend in stroke incidence rates over the past four decades, with a 42% decrease in stroke incidence in high-income countries and a greater than 100% increase in stroke incidence in low to middle income countries. In 2000-08, the overall stroke incidence rates in low to middle income countries have, for the first time, exceeded the level of stroke incidence seen in high-income countries, by 20%. The time to decide whether or not stroke is an issue that should be on the governmental agenda in low to middle income countries has now passed. Now is the time for action.

Global burden of blood-pressure-related disease, 2001.

BACKGROUND: Few studies have assessed the extent and distribution of the blood-pressure burden worldwide. The aim of this study was to quantify the global burden of disease related to high blood pressure. METHODS: Worldwide burden of disease attributable to high blood pressure (> or =115 mm Hg systolic) was estimated for groups according to age (> or =30 years), sex, and World Bank region in the year 2001. Population impact fractions were calculated with data for mean systolic blood pressure, burden of deaths and disability-adjusted life years (DALYs), and relative risk corrected for regression dilution bias. FINDINGS: Worldwide, 7.6 million premature deaths (about 13.5% of the global total) and 92 million DALYs (6.0% of the global total) were attributed to high blood pressure. About 54% of stroke and 47% of ischaemic heart disease worldwide were attributable to high blood pressure. About half this burden was in people with hypertension; the remainder was in those with lesser degrees of high blood pressure. Overall, about 80% of the attributable burden occurred in low-income and middle-income economies, and over half occurred in people aged 45-69 years. INTERPRETATION: Most of the disease burden caused by high blood pressure is borne by low-income and middle-income countries, by people in middle age, and by people with prehypertension. Prevention and treatment strategies restricted to individuals with hypertension will miss much blood-pressure-related disease.

Global and regional mortality from ischaemic heart disease and stroke attributable to higher-than-optimum blood glucose concentration: comparative risk assessment.

BACKGROUND: Cardiovascular mortality risk increases continuously with blood glucose, from concentrations well below conventional thresholds used to define diabetes. We aimed to quantify population-level effects of all higher-than-optimum concentrations of blood glucose on mortality from ischaemic heart disease and stroke worldwide. METHODS: We used population distribution of fasting plasma glucose to measure exposure to higher-than-optimum blood glucose. We collated exposure data in 52 countries from individual-level records in population health surveys, systematic reviews, and data provided by investigators. Relative risks for ischaemic heart disease and stroke mortality were from a meta-analysis of more than 200,000 participants in the Asia-Pacific region, with adjustment for other cardiovascular risk factors. RESULTS: In addition to 959,000 deaths directly assigned to diabetes, 1 490,000 deaths from ischaemic heart disease and 709,000 from stroke were attributable to high blood glucose, accounting for 21% and 13% of all deaths from these conditions. 1.8 million of these 2.2 million cardiovascular deaths (84%) were in low-and-middle-income countries (1,224,000 for ischaemic heart disease, 623,000 for stroke). 792,000 (53%) of deaths from ischaemic heart disease and 345,000 (49%) from stroke that were attributable to high blood glucose were in men. Largest numbers of deaths attributable to this risk factor from ischaemic heart disease were in low-and-middle-income countries of South Asia (548,000) and Europe and Central Asia (313,000), and from stroke in South Asia (215,000) and East Asia and Pacific (190,000). INTERPRETATION: Higher-than-optimum blood glucose is a leading cause of cardiovascular mortality in most world regions. Programmes for cardiovascular risk and diabetes management and control at the population level need to be more closely integrated.

Cardiovascular mortality attributable to high blood cholesterol in New Zealand.

OBJECTIVE: To estimate mortality attributable to higher-than-optimal blood cholesterol in New Zealand in 1997, and the mortality burden that could be potentially avoided in 2011 if modest reductions in mean population blood cholesterol concentrations were achieved. DESIGN: Comparative risk assessment methodology was used to estimate the attributable and avoidable mortality due to higher-than-optimal total blood cholesterol (> 3.8 mmol/L). Disease outcomes assessed were deaths from ischaemic heart disease (IHD) and ischaemic stroke. RESULTS: Overall, higher-than-optimal blood cholesterol contributed to 4,721 deaths in New Zealand in 1997 (17% of all deaths). This included 4,096 IHD deaths (64%) and 625 ischaemic stroke deaths (38%). Modest reductions in mean population blood cholesterol concentrations (e.g. 0.1 mmol/L) could potentially prevent 300 deaths (261 IHD and 39 ischaemic stroke) each year from 2011. CONCLUSIONS: Higher-than-optimal blood cholesterol concentrations are a leading cause of mortality in New Zealand. Modest reductions in blood cholesterol levels could have a major impact on population health within a decade.

Blood pressure and the global burden of disease 2000. Part II: estimates of attributable burden.

OBJECTIVES: To provide estimates of the global burden of disease attributable to non-optimal blood pressure by age and sex for adults aged > or = 30 years, by WHO subregion. METHODS: Estimates of attributable burden were made using population impact fractions, which used data on mean systolic blood pressure levels, disease burden [in deaths and/or disability-adjusted life years (DALYs)] and relative risk corrected for regression dilution bias. Estimates were made of burden attributable to a population distribution of blood pressure with a mean systolic blood pressure of greater than 115 mmHg. RESULTS: Globally, approximately two-thirds of stroke and one-half of ischaemic heart disease were attributable to non-optimal blood pressure. These proportions were highest in the more developed parts of the world. Worldwide, 7.1 million deaths (approximately 12.8% of the global total) and 64.3 million DALYs (4.4% of the global total) were estimated to be due to non-optimal blood pressure. Overall approximately, two-thirds of the attributable burden of disease occurred in the developing world, approximately two-thirds in the middle age groups (45-69 years) and approximately one-half occurred in those with systolic blood pressure levels between 130 and 150 mmHg. CONCLUSIONS: The burden of non-optimal blood pressure is almost double that of the only previous global estimates, which is largely explained by the correction for regression dilution adopted in these analyses. High blood pressure is a leading cause of global burden of disease, and most of it occurs in the developing world.

Rethinking the "diseases of affluence" paradigm: global patterns of nutritional risks in relation to economic development.

BACKGROUND: Cardiovascular diseases and their nutritional risk factors--including overweight and obesity, elevated blood pressure, and cholesterol--are among the leading causes of global mortality and morbidity, and have been predicted to rise with economic development. METHODS AND FINDINGS: We examined age-standardized mean population levels of body mass index (BMI), systolic blood pressure, and total cholesterol in relation to national income, food share of household expenditure, and urbanization in a cross-country analysis. Data were from a total of over 100 countries and were obtained from systematic reviews of published literature, and from national and international health agencies. BMI and cholesterol increased rapidly in relation to national income, then flattened, and eventually declined. BMI increased most rapidly until an income of about ID 5,000 (international dollars) and peaked at about ID 12,500 for females and ID 17,000 for males. Cholesterol's point of inflection and peak were at higher income levels than those of BMI (about ID 8,000 and ID 18,000, respectively). There was an inverse relationship between BMI/cholesterol and the food share of household expenditure, and a positive relationship with proportion of population in urban areas. Mean population blood pressure was not correlated or only weakly correlated with the economic factors considered, or with cholesterol and BMI. CONCLUSIONS: When considered together with evidence on shifts in income-risk relationships within developed countries, the results indicate that cardiovascular disease risks are expected to systematically shift to low-income and middle-income countries and, together with the persistent burden of infectious diseases, further increase global health inequalities. Preventing obesity should be a priority from early stages of economic development, accompanied by population-level and personal interventions for blood pressure and cholesterol.

Effectiveness and costs of interventions to lower systolic blood pressure and cholesterol: a global and regional analysis on reduction of cardiovascular-disease risk.

BACKGROUND: Cardiovascular disease accounts for much morbidity and mortality in developed countries and is becoming increasingly important in less developed regions. Systolic blood pressure above 115 mm Hg accounts for two-thirds of strokes and almost half of ischaemic heart disease cases, and cholesterol concentrations exceeding 3.8 mmol/L for 18% and 55%, respectively. We report estimates of the population health effects, and costs of selected interventions to reduce the risks associated with high cholesterol concentrations and blood pressure in areas of the world with differing epidemiological profiles. METHODS: Effect sizes were derived from systematic reviews or meta-analyses, and the effect on health outcomes projected over time for populations with differing age, sex, and epidemiological profiles. Incidence data from estimates of burden of disease were used in a four-state longitudinal population model to calculate disability-adjusted life years (DALYs) averted and patients treated. Costs were taken from previous publications, or estimated by local experts, in 14 regions. FINDINGS: Non-personal health interventions, including government action to stimulate a reduction in the salt content of processed foods, are cost-effective ways to limit cardiovascular disease and could avert over 21 million DALYs per year worldwide. Combination treatment for people whose risk of a cardiovascular event over the next 10 years is above 35% is also cost effective leading to substantial additional health benefits by averting an additional 63 million DALYs per year worldwide. INTERPRETATION: The combination of personal and non-personal health interventions evaluated here could lower the global incidence of cardiovascular events by as much as 50%.