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Persistent depression doubled coronary heart disease risk

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Depression may be a marker of occult vascular disease

This is an interesting study in a large number of patients that suggests – to my knowledge, for the first time – that the association of depression with stroke may be "reverse causation," meaning that some vascular abnormality contributes to the depression and not necessarily that the depression is directly related to the stroke.

In contrast, depression does seem to be related to developing coronary heart disease. The findings are interesting. They support what many have thought for years, that depression is a risk factor for heart disease.

On the other hand, the idea that depression may be a marker of occult vascular disease that can lead to a stroke is novel, but needs careful confirmation because it has not been shown previously. Previous studies suggest that depression is a risk factor for stroke more directly, like the coronary heart disease relationship.

Dr. Paul Thompson is medical director of cardiology and the Athletes’ Heart Program at Hartford Hospital and professor of medicine at the University of Connecticut. Dr. Thompson said he had no relevant conflicts of interest to disclose.


 

FROM THE EUROPEAN JOURNAL OF PREVENTATIVE CARDIOLOGY

Depressive symptoms significantly increased the risk of coronary heart disease in a long-term study of more than 10,000 patients, suggesting that depression may be a modifiable cardiovascular risk factor.

Data from the prospective cohort Whitehall II study showed a dose-dependent increase in CHD risk with repeated observation of depressive symptoms. The presence of depressive symptoms identified on one or two occasions using the 30-item General Health Questionnaire (GHQ-30) was associated with a significant 12% increase in CHD risk (hazard ratio, 1.12). However, if depressive symptoms were recorded at three or four assessment points, the risk of CHD risk doubled significantly (HR, 2.06).

Depression was also measured using the more specific Center for Epidemiologic Studies Depression Scale (CES-D), with a significant 81% increase in CHD risk if depressive symptoms were evident (HR, 1.81).

In contrast, significant positive associations between depression and the development of stroke seen in the first 5 years of follow-up in the study (HR, 1.6) were not sustained in the long term (HR, 0.94 at 5-10 years’ follow-up).

The Whitehall II study began in 1985 to look at the long-term importance of social class on health. A baseline survey and subsequent clinical examination resulted in 10,308 men and women aged 35-55 years being recruited from 1985 to 1988. Clinical examinations were undertaken every 5 years, with postal surveys undertaken in between, and included the completion of the GHQ-30. The 20-item CES-D was also completed during one assessment period, between 2003 and 2009.

The results from the GHQ-30 were validated against clinical interviews, with a score of 0 representing no change and higher scores reflecting an increase in depressive symptoms. GHQ-30 "caseness" was defined as a score of 5 or more. CES-D caseness was defined as a score of 16 or more out of a maximum of 60.

National databases and records were used to identify cases of fatal and nonfatal cardiovascular events, stroke, and associated mortality. The MONICA-Augsburg Stroke Symptom Questionnaire was used to capture clinical symptoms of stroke, in addition to self-reported events collected throughout the study.

The mean age of participants at the first GHQ-30 measurement was 44 years, and was 61 years by the fourth assessment in 2003-2004. The majority (90%) of participants described themselves as white, and 67% of the cohort was male.

"We investigated the possibility of reverse causation by examining the association between prevalent major CHD or prevalent stroke with subsequent incidence of GHQ-30 caseness," the Whitehall II investigators noted in the study, which was published online in the European Journal of Preventative Cardiology (doi:10.1177/2047487314520785).

Although they found weak evidence that CHD was significantly associated with subsequent GHQ-30 caseness (odds ratio, 1.32), they did find a significant association between prevalent stroke and depressive symptoms (OR, 2.01).

It is not clear why depressive symptoms might be causally linked to CHD but not stroke. One plausible explanation is that it could be linked to blood pressure – a particularly important risk factor for stroke, but only one of many for CHD. Depressive symptoms have been linked to low blood pressure, "and this inverse association would tend to confound the association with stroke to a greater extent than with CHD," the authors noted. Antihypertensive medications might also be causing depression or psychological distress, the authors suggested.

"European prevention guidelines refer to depression as a coronary risk factor," noted lead author Dr. Eric Brunner of University College London in a press release issued by the European Society of Cardiology. "In our study, repeated episodes of depressive symptoms accounted for 10% of all CHD events in the study population." That figure suggests the existence of a causal relationship between depression and heart disease.

"Whether or not the association is causal, supporting individuals to recover from chronic or repeated episodes of depression has merit, particularly if the individual is then better able to reduce any vascular risk – for example, by quitting smoking."

More research is needed to examine the uncertainties regarding depression as a causal factor in CHD and stroke, Dr. Brunner and his associates concluded.

The research was funded by grants from the British Medical Research Council, the British Heart Foundation, the British Health and Safety Executive, the British Department of Health, the British Stroke Association, the U.S. National Heart, Lung, and Blood Institute, and the U.S. National Institute on Aging. The investigators had no conflicts of interest to disclose.

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