Inflammation Not Behind Depression/CHD Link

Major Finding: Each standard deviation rise in level of depressive symptoms at baseline, as assessed from CES-D score, was associated with a 26% increase in the risk of a first CHD event after inflammatory markers were taken into account.

Data Source: A population-based study of 1,794 randomly selected Nova Scotians with prospective 10-year follow-up.

Disclosures: Dr. Davidson reported that she had no relevant conflicts of interest.

VANCOUVER, B.C. — Depression increases the risk of coronary heart disease, but it does not do so through proinflammatory mechanisms, a study has shown.

In 1,794 healthy Nova Scotians randomly selected from the general population, those with higher levels of depressive symptoms did indeed have higher levels of inflammatory biomarkers.

But after these markers and traditional risk factors were taken into account, depressive symptoms still predicted first coronary heart disease (CHD) events over the next decade, with the risk rising by 26% with each standard deviation increase in Center for Epidemiologic Studies–Depression (CES-D) score.

“Inflammatory biomarkers neither fully nor partially explained the association between depression and CHD,” lead investigator Karina W. Davidson, Ph.D., said at the congress.

“We have also looked into recurrent CHD, and we did not find it,” she added. “So we are concluding that we need to explore other biological mechanisms, such as platelet aggregation or endothelial dysfunction.”

Several scenarios have been proposed to explain associations among depressive symptoms, inflammation, and CHD (Am. J. Cardiol. 2005;96:1016–21), according to Dr. Davidson of the department of medicine at Columbia University Medical Center in New York. In some of these scenarios, depression has effects on physiology or behavior that promote the development of CHD.

These effects could be indirect (for example, nonadherence to cardiac prevention regimens, increased unfavorable lifestyle behaviors, or cardiotoxicity of antidepressants) or direct (for example, increased inflammation, endothelial dysfunction, enhanced platelet aggregation, or autonomic and neuroendocrine perturbations).

“Depressive symptoms and inflammatory markers have been highly comorbid in a number of studies, so we felt this was a promising pattern to look at, whether inflammatory markers serve perhaps as the mechanism,” she explained.

Dr. Davidson and her colleagues studied apparently healthy adults recruited to the population-based Canadian Nova Scotia Health Survey in 1995.

At baseline, study participants underwent assessment of traditional risk factors such as lipids and smoking, completed the CES-D, and gave a blood sample for measurement of three inflammatory markers: high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule (sICAM), and interleukin-6.

The study population was 46 years old on average and equally divided by sex. Participants' mean body mass index was about 27 kg/m

Participants had a mean score on the CES-D scale of 7.2 points out of a possible 60, with a standard deviation of 7.7 points. Only 3% of participants were taking antidepressants.

During a prospective 10-year follow-up, 8.5% of participants had a first CHD event, as ascertained from diagnostic codes on hospital admissions or death certificates, Dr. Davidson reported.

Each standard deviation increase in depressive symptoms was associated with an 8.3% higher hs-CRP level and a 4.7% higher interleukin-6 level.

In analyses adjusted for traditional risk factors, the higher participants' level of depressive symptoms, the greater their risk of CHD events, with a significant 28% greater risk for each standard deviation increase in CES-D score, she said.

The risk of events also rose with hs-CRP level and sICAM level (but not interleukin-6 level) at baseline, independent of traditional risk factors.

When all of the variables were included in a model, a higher level of depressive symptoms still significantly predicted a greater likelihood of CHD events, with a significant 26% greater risk for each standard deviation increase in CES-D score.

Furthermore, this association was consistent across a variety of subgroups: men, current smokers, participants aged 65 years or older, obese participants, those not prescribed any cardiac medications (although statins were not assessed), and those not prescribed antidepressants.

“Depression and inflammation are moderately correlated,” commented Dr. Davidson, but “depressive symptoms were independent for CHD, and inflammation was independent for CHD — there did not seem to be any kind of mechanistic association amongst them,” she added.

“We still believe in our hearts that there are some patients who have cytokine-induced depression,” Dr. Davidson concluded. “We are now trying the hypothesis that there may be a small, intermediary phenotype of depressed persons who actually have very high cytokines, and they may go on to have a higher rate of incident CHD, and we are testing them.”

Major Finding: Each standard deviation rise in level of depressive symptoms at baseline, as assessed from CES-D score, was associated with a 26% increase in the risk of a first CHD event after inflammatory markers were taken into account.

Data Source: A population-based study of 1,794 randomly selected Nova Scotians with prospective 10-year follow-up.

Disclosures: Dr. Davidson reported that she had no relevant conflicts of interest.

VANCOUVER, B.C. — Depression increases the risk of coronary heart disease, but it does not do so through proinflammatory mechanisms, a study has shown.

In 1,794 healthy Nova Scotians randomly selected from the general population, those with higher levels of depressive symptoms did indeed have higher levels of inflammatory biomarkers.

But after these markers and traditional risk factors were taken into account, depressive symptoms still predicted first coronary heart disease (CHD) events over the next decade, with the risk rising by 26% with each standard deviation increase in Center for Epidemiologic Studies–Depression (CES-D) score.

“Inflammatory biomarkers neither fully nor partially explained the association between depression and CHD,” lead investigator Karina W. Davidson, Ph.D., said at the congress.

“We have also looked into recurrent CHD, and we did not find it,” she added. “So we are concluding that we need to explore other biological mechanisms, such as platelet aggregation or endothelial dysfunction.”

Several scenarios have been proposed to explain associations among depressive symptoms, inflammation, and CHD (Am. J. Cardiol. 2005;96:1016–21), according to Dr. Davidson of the department of medicine at Columbia University Medical Center in New York. In some of these scenarios, depression has effects on physiology or behavior that promote the development of CHD.

These effects could be indirect (for example, nonadherence to cardiac prevention regimens, increased unfavorable lifestyle behaviors, or cardiotoxicity of antidepressants) or direct (for example, increased inflammation, endothelial dysfunction, enhanced platelet aggregation, or autonomic and neuroendocrine perturbations).

“Depressive symptoms and inflammatory markers have been highly comorbid in a number of studies, so we felt this was a promising pattern to look at, whether inflammatory markers serve perhaps as the mechanism,” she explained.

Dr. Davidson and her colleagues studied apparently healthy adults recruited to the population-based Canadian Nova Scotia Health Survey in 1995.

At baseline, study participants underwent assessment of traditional risk factors such as lipids and smoking, completed the CES-D, and gave a blood sample for measurement of three inflammatory markers: high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule (sICAM), and interleukin-6.

The study population was 46 years old on average and equally divided by sex. Participants' mean body mass index was about 27 kg/m

Participants had a mean score on the CES-D scale of 7.2 points out of a possible 60, with a standard deviation of 7.7 points. Only 3% of participants were taking antidepressants.

During a prospective 10-year follow-up, 8.5% of participants had a first CHD event, as ascertained from diagnostic codes on hospital admissions or death certificates, Dr. Davidson reported.

Each standard deviation increase in depressive symptoms was associated with an 8.3% higher hs-CRP level and a 4.7% higher interleukin-6 level.

In analyses adjusted for traditional risk factors, the higher participants' level of depressive symptoms, the greater their risk of CHD events, with a significant 28% greater risk for each standard deviation increase in CES-D score, she said.

The risk of events also rose with hs-CRP level and sICAM level (but not interleukin-6 level) at baseline, independent of traditional risk factors.

When all of the variables were included in a model, a higher level of depressive symptoms still significantly predicted a greater likelihood of CHD events, with a significant 26% greater risk for each standard deviation increase in CES-D score.

Furthermore, this association was consistent across a variety of subgroups: men, current smokers, participants aged 65 years or older, obese participants, those not prescribed any cardiac medications (although statins were not assessed), and those not prescribed antidepressants.

“Depression and inflammation are moderately correlated,” commented Dr. Davidson, but “depressive symptoms were independent for CHD, and inflammation was independent for CHD — there did not seem to be any kind of mechanistic association amongst them,” she added.

“We still believe in our hearts that there are some patients who have cytokine-induced depression,” Dr. Davidson concluded. “We are now trying the hypothesis that there may be a small, intermediary phenotype of depressed persons who actually have very high cytokines, and they may go on to have a higher rate of incident CHD, and we are testing them.”

Major Finding: Each standard deviation rise in level of depressive symptoms at baseline, as assessed from CES-D score, was associated with a 26% increase in the risk of a first CHD event after inflammatory markers were taken into account.

Data Source: A population-based study of 1,794 randomly selected Nova Scotians with prospective 10-year follow-up.

Disclosures: Dr. Davidson reported that she had no relevant conflicts of interest.

VANCOUVER, B.C. — Depression increases the risk of coronary heart disease, but it does not do so through proinflammatory mechanisms, a study has shown.

In 1,794 healthy Nova Scotians randomly selected from the general population, those with higher levels of depressive symptoms did indeed have higher levels of inflammatory biomarkers.

But after these markers and traditional risk factors were taken into account, depressive symptoms still predicted first coronary heart disease (CHD) events over the next decade, with the risk rising by 26% with each standard deviation increase in Center for Epidemiologic Studies–Depression (CES-D) score.

“Inflammatory biomarkers neither fully nor partially explained the association between depression and CHD,” lead investigator Karina W. Davidson, Ph.D., said at the congress.

“We have also looked into recurrent CHD, and we did not find it,” she added. “So we are concluding that we need to explore other biological mechanisms, such as platelet aggregation or endothelial dysfunction.”

Several scenarios have been proposed to explain associations among depressive symptoms, inflammation, and CHD (Am. J. Cardiol. 2005;96:1016–21), according to Dr. Davidson of the department of medicine at Columbia University Medical Center in New York. In some of these scenarios, depression has effects on physiology or behavior that promote the development of CHD.

These effects could be indirect (for example, nonadherence to cardiac prevention regimens, increased unfavorable lifestyle behaviors, or cardiotoxicity of antidepressants) or direct (for example, increased inflammation, endothelial dysfunction, enhanced platelet aggregation, or autonomic and neuroendocrine perturbations).

“Depressive symptoms and inflammatory markers have been highly comorbid in a number of studies, so we felt this was a promising pattern to look at, whether inflammatory markers serve perhaps as the mechanism,” she explained.

Dr. Davidson and her colleagues studied apparently healthy adults recruited to the population-based Canadian Nova Scotia Health Survey in 1995.

At baseline, study participants underwent assessment of traditional risk factors such as lipids and smoking, completed the CES-D, and gave a blood sample for measurement of three inflammatory markers: high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule (sICAM), and interleukin-6.

The study population was 46 years old on average and equally divided by sex. Participants' mean body mass index was about 27 kg/m

Participants had a mean score on the CES-D scale of 7.2 points out of a possible 60, with a standard deviation of 7.7 points. Only 3% of participants were taking antidepressants.

During a prospective 10-year follow-up, 8.5% of participants had a first CHD event, as ascertained from diagnostic codes on hospital admissions or death certificates, Dr. Davidson reported.

Each standard deviation increase in depressive symptoms was associated with an 8.3% higher hs-CRP level and a 4.7% higher interleukin-6 level.

In analyses adjusted for traditional risk factors, the higher participants' level of depressive symptoms, the greater their risk of CHD events, with a significant 28% greater risk for each standard deviation increase in CES-D score, she said.

The risk of events also rose with hs-CRP level and sICAM level (but not interleukin-6 level) at baseline, independent of traditional risk factors.

When all of the variables were included in a model, a higher level of depressive symptoms still significantly predicted a greater likelihood of CHD events, with a significant 26% greater risk for each standard deviation increase in CES-D score.

Furthermore, this association was consistent across a variety of subgroups: men, current smokers, participants aged 65 years or older, obese participants, those not prescribed any cardiac medications (although statins were not assessed), and those not prescribed antidepressants.

“Depression and inflammation are moderately correlated,” commented Dr. Davidson, but “depressive symptoms were independent for CHD, and inflammation was independent for CHD — there did not seem to be any kind of mechanistic association amongst them,” she added.

“We still believe in our hearts that there are some patients who have cytokine-induced depression,” Dr. Davidson concluded. “We are now trying the hypothesis that there may be a small, intermediary phenotype of depressed persons who actually have very high cytokines, and they may go on to have a higher rate of incident CHD, and we are testing them.”