Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87–0.94), with an additional relative risk for CVD of 0.92 (0.87–0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75–0.93), 0.76 (0.67–0.85), 0.69 (0.59–0.79), or 0.63 (0.52–0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Congenital heart disease (CHD) is the leading cause of morbidity and mortality from birth defects worldwide. We report an overview of trends in CHD mortality in 204 countries and territories over the past 30 years and associations with age, period, and birth cohort. Cause-specific CHD mortality estimates were derived from the Global Burden of Disease 2019 study. We utilised an age-period-cohort model to estimate overall annual percentage changes in mortality (net drifts), annual percentage changes from 0 to 4 to 65–69 years (local drifts), period and cohort relative risks (period/cohort effects) between 1990 and 2019. This approach allows for the examination and differentiation of age, period, and cohort effects in the mortality trends, with the potential to identify disparities and treatment gaps in cardiac care. CHD is the leading cause of deaths from non-communicable diseases (NCDs) in those under 20 years. Global CHD deaths in 2019 were 217,000 (95% uncertainty interval 177,000–262,000). There were 129 countries with at least 50 deaths. India, China, Pakistan, and Nigeria had the highest mortality, accounting for 39.7% of deaths globally. Between 1990 and 2019, the net drift of CHD mortality ranged from –2.41% per year (95% confidence interval [CI] –2.55, –2.67) in high Socio-demographic Index (SDI) countries to –0.62% per year (95% CI: –0.82, –0.42) in low-SDI countries. Globally, there was an emerging transition in the age distribution of deaths from paediatric to adult populations, except for an increasing trend of mortality in those aged 10–34 years in Mexico and Pakistan. During the past 30 years, favourable mortality reductions were generally found in most high-SDI countries like South Korea (net drift = –4.0% [95% CI –4.8 to –3.1] per year) and the United States (–2.3% [–2.5 to –2.0]), and also in many middle-SDI countries like Brazil (–2.7% [–3.1 to 2.4]) and South Africa (–2.5% [–3.2 to –1.8]). However, 52 of 129 countries had either increasing trends (net drifts ≥0.0%) or stagnated reductions (≥–0.5%) in mortality. The relative risk of mortality generally showed improving trends over time and in successively younger birth cohorts amongst high- and high-middle-SDI countries, with the exceptions of Saudi Arabia and Kazakhstan. 14 middle-SDI countries such as Ecuador and Mexico, and 16 low-middle-SDI countries including India and 20 low-SDI countries including Pakistan, had unfavourable or worsening risks for recent periods and birth cohorts. CHD mortality is a useful and accessible indicator of trends in the provision of congenital cardiac care both in early childhood and across later life. Improvements in the treatment of CHD should reduce the risk for successively younger cohorts and shift the risk for all age groups over time. Although there were gains in CHD mortality globally over the past three decades, unfavourable period and cohort effects were found in many countries, raising questions about adequacy of their health care for CHD patients across all age groups. These failings carry significant implications for the likelihood of achieving the Sustainable Development Goal targets for under-5 years and NCD mortality. Supported by the 10.13039/501100001809 National Natural Science Foundation of China (81525002, 31971048, 82073573 to ZZ and HZ), Shanghai Outstanding Medical Academic Leader program (2019LJ22 to HZ), and Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01 to HZ), the Bill & Melinda Gates Foundation for the Global Burden of Disease Project (to NJK) and NHMRC fellowship administered through the University of Melbourne (to GCP).

Background: Brazil, Russia, India, China, and South Africa (BRICS) are emerging economies making up almost half the global population. We analyzed trends in cardiovascular disease (CVD) mortality across the BRICS and associations with age, period, and birth cohort. Methods: Mortality estimates were derived from the Global Burden of Disease Study 2017. We used age-period-cohort modeling to estimate cohort and period effects in CVD between 1992 and 2016. Period was defined as survey year, and period effects reflect population-wide exposure at a circumscribed point in time. Cohort effects are defined as differences in risks across birth cohort. Net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks were calculated. Results: In 2016, there were 8.4 million CVD deaths across the BRICS. Between 1992 and 2016, the reduction in CVD age-standardized mortality rate in BRICS (−17%) was less than in North America (−39%). Eighty-eight percent of the increased number of all-cause deaths resulted from the increase in CVD deaths. The age-standardized mortality rate from stroke and hypertensive heart disease declined by approximately one-third across the BRICS, whereas ischemic heart disease increased slightly (2%). Brazil had the largest age-standardized mortality rate reductions across all CVD categories, with improvement both over time and in recent birth cohorts. South Africa was the only country where the CVD age-standardized mortality rate increased. Different age-related CVD mortality was seen in those ≥50 years of age in China, ≤40 years of age in Russia, 35 to 60 years of age in India, and ≥55 years of age in South Africa. Improving period and cohort risks for CVD mortality were generally found across countries, except for worsening period effects in India and greater risks for ischemic heart disease in Chinese cohorts born in the 1950s and 1960s. Conclusions: Except for Brazil, reductions of CVD mortality across the BRICS have been less than that in North America, such that China, India, and South Africa contribute an increasing proportion of global CVD deaths. Brazil’s example suggests that prevention policies can both reduce the risks for younger birth cohorts and shift the risks for all age groups over time.

Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.