Evidence supports link between AMD, cardiovascular disease
Results of four studies suggest that ophthalmologists and cardiologists should consider the common risk factors.
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Cross-disciplinary awareness of the shared risk factors between cardiovascular disease and age-related macular degeneration is important in treating patients with either disease. Researchers, however, appear to differ on the degree of association.
“More data supporting the association between cardiovascular disease (CVD) and late stages of AMD are continuing to emerge,” Usha Chakravarthy, MD, FRCS, PhD, told Ocular Surgery News in an e-mail interview.
“Better vascular compliance and regulation of the ocular circulation through improved and early management of the systemic manifestations of cardiovascular disease could in the long term prove beneficial in reducing the risk of development of the late stages of AMD,” she said.
Evidence for a link between CVD and AMD has been building over the past 10 years as researchers have added to the list of possible common risk factors. Recent studies have shown a link between CVD and AMD, and blood pressure, body mass index and cholesterol.
“One of the likely common pathways would be [the] inflammatory process,” Jie Jin Wang, MMed, PhD, told OSN.
“Other possible pathways could involve antioxidants and omega-3 fatty acids, but the exact mechanisms are less clear,” she said.
Research remains largely inconclusive, as some investigators find connections between risk factors, while others do not. Most experts agree that a link likely exists, and so neither ophthalmologists nor cardiologists can ignore the common factors across their specialties.
Evidence for a link
In a study published in the British Journal of Ophthalmology, Dr. Wang and colleagues showed that AMD patients aged 49 to 75 years were at a higher risk of having a stroke or other cardiovascular event.
Specifically, the investigators followed 1,952 older Australians recruited in the longitudinal Blue Mountains Eye Study, led by Paul Mitchell, MBBS, MD, PhD, FRANZCO, FRACS, FRCOphth, FAFPHM, for 10 years. They found that early AMD predicted a twofold higher risk of cardiovascular mortality, controlling for cardiovascular risk factors, whereas late AMD predicted a fivefold higher risk of cardiovascular mortality, controlling for age and sex.
In a study published in Ophthalmology, the same investigators found that a self-reported history of stroke and any CVD at baseline (1992 to 1994) in the same study population predicted early AMD development over the next 10 years.
Similarly, in a case-control study involving more than 400 participants, Dr. Chakravarthy and colleagues found that the odds of having a history of existing CVD were far higher in cases of neovascular AMD than in controls. Their results were published in Ophthalmology.
“Our study cannot confirm causality, but it is strongly suggestive,” she said.
Common risk factors
Recent studies have found cholesterol, body mass and hypertension to be associated with AMD development.
In the Blue Mountains Eye Study article, Drs. Mitchell and Wang and colleagues said elevated total/high-density lipoprotein cholesterol ratio predicted late AMD, controlling for diabetes, heavy alcohol consumption and total cholesterol. They also said patients in the top four quintiles of high-density lipoprotein cholesterol were significantly less likely to develop late AMD than those in the lowest quintiles, controlling for age, gender and smoking.
In their study, Dr. Chakravarthy and colleagues found cholesterol to be linked to neovascular AMD as well, but they also found associations with body mass and hypertension.
Specifically, patients in the highest quartile of body mass index and those with stage 2 hypertension were more likely to have wet AMD. Dr. Chakravarthy pointed to hypertension as the most significant common risk factor.
Latino population study
In a separate study, Rohit Varma, MD, MPH, and colleagues evaluated the link between CVD and AMD in a Latino population. Their results were published in the American Journal of Ophthalmology.
Rohit Varma |
Dr. Varma told OSN that the authors were interested in the connection because their population demonstrated a high prevalence of obesity, diabetes and high blood pressure, all factors previously linked to AMD.
In a population-based sample of 5,875 Latino patients, rates of high diastolic blood pressure and uncontrolled diastolic hypertension were higher among patients with exudative AMD, they reported.
Additionally, the researchers found a higher rate of obesity among patients who showed increased retinal pigment.
“One essential piece of evidence that is needed before one can begin to plan clinical trials and intervention programs is that you want to have some common factors that you can address across the board, not just in one ethnic group but in different ethnic groups,” Dr. Varma said.
“What we have provided is additional evidence from a completely different ethnic group that supports some of the findings that were seen in non-Hispanic whites, and thus it strengthens the case that can be made for smoking and blood pressure and perhaps indirectly inflammation and its role in the development of advanced AMD,” he said.
Investigation into the connection between CVD and AMD is just like any other line of research, Dr. Varma said: “You build the evidence one step at a time until you reach a critical mass when you say, ‘OK, now let’s find a way to intervene and see if it really has an impact.’”
Patient, physician action
In the meantime, researchers have begun to consider the existence of CVD-related therapeutic tactics for AMD patients.
“A preliminary impression at this stage is that what is good for the heart appears also to be good for the eye,” Dr. Wang said. “These would include antioxidants, omega-3 fatty acids and reduced glycemic index diet.
“Advising patients to lead a healthier lifestyle, including diet, exercise and approaches to minimize CVD risk factors, will be good for the heart as well as for the eye,” she said.
Dr. Varma agreed on the use of antioxidants and also mentioned zinc as a possible useful dietary supplement for patients at high risk for AMD. Additionally, he said patients may reduce their risk of developing AMD by quitting smoking and controlling their blood pressure. He noted that more evidence is needed to definitively link smoking and blood pressure to AMD, but “those two areas have been the most consistent ones in most studies.”
“The other thing, which is still very much in an early stage, is that in the last few years, researchers have identified a group of genes — the CFH gene complex (complement factor H) — which is related to an inflammatory pathway,” Dr. Varma said.
“If inflammation is related to AMD, and it appears to be, then would it be valuable to use anti-inflammatory medications directed specifically at this pathway to lower the risk of developing advanced AMD?” he said, adding that this cutting-edge research is an area that deserves attention in the future.
Future studies
“In general, many different study designs are needed to examine the consistency and coherence of the evidence, including animal models and basic science research,” Dr. Wang said.
However, researchers identified a number of roadblocks in the way of research that can produce fruitful conclusions while avoiding the bias that is inherent when using data from cases seen in hospital clinics.
“Unfortunately, the numbers with late AMD in population-based prevalence studies are low,” Dr. Chakravarthy said. “This is even more of a problem for studies involving incident cases, as these are fewer still.
“The other major problem is that the relationship between drusen and pigmentary irregularities (considered to be the precursor for late AMD) show inconsistent relationships with the risk factors,” she said. “Therefore, even though these early features of AMD are very common, the longitudinal studies have not been able to demonstrate consistent relationships between CVD and early AMD.”
Dr. Varma said studies are sometimes limited in terms of population, as some groups are at a higher risk of developing AMD than others.
He said a study involving older patients of European ancestry who are at high risk of developing AMD would be useful in evaluating the effects of smoking and blood pressure. Such a study could introduce both smoking cessation and blood pressure control to half the population, while leaving the other half as is. Investigators could then determine the rate of advanced AMD development and evaluate the efficacy of this approach.
“The other possibility is to obtain a measure of vascular compliance that is more robust (such as pulse wave amplitude) and measure this in a high-risk group and follow them up to the point where they develop late AMD,” Dr. Chakravarthy said.
For more information:
- Usha Chakravarthy, MD, FRCS, PhD, can be reached at the Centre for Vision Science, Queens University Belfast, ICS Block A RVH, Grosvenor Road, Belfast BT12 6BA, United Kingdom; 44-28-90633954; fax: 44-28-90632699; u.chakravarthy@qub.ac.uk.
- Rohit Varma, MD, MPH, can be reached at Doheny Eye Institute, 1450 San Pablo St., Suite 4900, Los Angeles, CA 90033; 323-442-6411; fax: 323-442-6412; rvarma@usc.edu.
- Jie Jin Wang, MMed, PhD, can be reached at Westmead Hospital, Hawkesbury Road, Westmead, New South Wales 2145, Australia; e-mail: jiejin_wang@wmi.usyd.edu.au.
References:
- Fraser-Bell S, Wu J, et al. Cardiovascular risk factors and age-related macular degeneration: The Los Angeles Latino Eye Study. Am J Ophthalmol. 2008; 145: 308-316.
- Hogg RE, Woodside JV, et al. Cardiovascular disease and hypertension are strong risk factors for choroidal neovascularization. Ophthalmology. 2008;115:1046-1052.
- Tan JS, Mitchell P, Smith W, Wang JJ. Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: The Blue Mountains Eye Study. Ophthalmology. 2007;114:1143-1150.
- Tan JS, Wang JJ, et al. Age-related macular degeneration and mortality from cardiovascular disease or stroke. Br J Ophthalmol. 2008; 92:509-512.
- Jessica Loughery is an OSN Correspondent who is based in Philadelphia.