Person:

Wu, Juan

Importance Research has indicated some shared pathogenic mechanisms between age-related macular degeneration (AMD) and cardiovascular disease (CVD). However, results from prior epidemiologic studies have been inconsistent as to whether AMD is predictive of future CVD risk. Objective: To systematically review population-based cohort studies of the association between AMD and risk of total CVD and CVD subtypes, coronary heart disease (CHD) and stroke. Data Sources A systematic search of the PubMed and EMBASE databases and reference lists of key retrieved articles up to December 20, 2012 without language restriction. Data Extraction Two reviewers independently extracted data on baseline AMD status, risk estimates of CVD and methods used to assess AMD and CVD. We pooled relative risks using random or fixed effects models as appropriate. Results: Thirteen cohort studies (8 prospective and 5 retrospective studies) with a total of 1,593,390 participants with 155,500 CVD events (92,039 stroke and 62,737 CHD) were included in this meta-analysis. Among all studies, early AMD was associated with a 15% (95% CI, 1.08–1.22) increased risk of total CVD. The relative risk was similar but not significant for late AMD (RR, 1.17; 95% CI, 0.98–1.40). In analyses restricted to the subset of prospective studies, the risk associated with early AMD did not appreciably change; however, there was a marked 66% (95% CI, 1.31–2.10) increased risk of CVD among those with late AMD. Conclusion: Whereas the results from all cohort studies suggest that both early and late AMD are predictive of a small increase in risk of future CVD, subgroup analyses limited to prospective studies demonstrate a markedly increased risk of CVD among people with late AMD. Retrospective studies using healthcare databases may have inherent methodological limitations that obscure such association. Additional prospective studies are needed to further elucidate the associations between AMD and specific CVD outcomes.

Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in older Americans. There has been a long standing interest in the role of diet in the development of AMD. As early as the first National Health and Nutrition Examination Survey in the 1970s, higher intakes of fruits and vegetables were inversely correlated with the prevalence of AMD. Carotenoids and omega3 fatty acids are the most studied dietary factors due to strong biological plausibility. However, evidence from epidemiologic studies and clinical trials on the relations has been inconsistent. Chapter I prospectively examined the intakes of lutein/zeaxanthin and other common carotenoids in relation to the risk of AMD over more than two decades of follow-up among two large US cohorts, the Nurses’ Health Study and Health Professionals Follow-Up Study. We assessed nutrient intakes by repeated food frequency questionnaires. We also computed bioavailable plasma carotenoid scores directly from food intake using validated regression models. Cox proportional hazards models were used to compute the associations. Higher intakes of bioavailable carotenoids (except lycopene) were inversely associated with advanced AMD but not intermediate AMD. Analyses based on bioavailable intakes resulted in stronger associations than conventional nutrient intakes. Chapter II prospectively evaluated the marine long-chain omega3 fatty acids. We found that long-chain omega3 fatty acids were inversely associated with visually significant intermediate AMD. There was no association with advanced AMD; however, the totality of current evidence for advanced AMD is also discordant. Chapter III further investigated the plant-derived omega3 fatty acids, α-linolenic acid (ALA). We found that higher intake of ALA was associated with intermediate AMD before 2002 but not after. This coincides with the same time period when trans ALA was found in our participants’ blood and in mayonnaise, a primary food source of ALA. Whether trans ALA mediates this positive association warrants further studies. Although randomized trials are usually believed as the “gold standard”, dietary factors are hard to be adequately studied by randomized trials due to the complexities of diet and disease relations. Thus, findings in this thesis from large long-term prospective cohort studies provide the next best form of evidence.