More Medical Comorbidities Among Bipolar Population
Goldstein and colleagues interpreted data from the National Epidemiological Survey in 2001-2002 that included 41,682 representative adults in the U.S. population sampled compared with 1,411 found in the community with a diagnosis of bipolar disorder.
Those with bipolar disorder had a 3.86 times higher odds of having coronary heart disease compared with those in the general population. They were also 2.15 times more likely to have hypertension. Most disturbingly, the mean age of those with coronary heart disease in the general population was 62.1 years of age, but in those with bipolar illness, it was 50.4 years of age. This indicates that the markedly increased risk and incidence of coronary artery disease occurred approximately 11 years earlier in those with bipolar illness compared with those without. Most interestingly, the number of prior depressive episodes correlated with the presence of either coronary heart disease or hypertension.
These data are also compatible with those reported in a poster by Ice et al., which showed a high incidence of metabolic abnormalities in patients with bipolar disorder: 64% of this same group were overweight or obese, 31% had elevated triglycerides, 14% had increased glucose levels, 28% had hypertension, and 42% had abnormally low levels of high-density lipoproteins (i.e. good cholesterol). They found that adjunctive ziprasidone treatment was associated with positive effects on weight and metabolic profiles during long-term maintenance treatment. Another poster by Jerrell et al. indicated that many of these adverse medical changes begin in those with bipolar disorder in adolescence.
There appear to be multiple interacting factors elevating the risk of cardiovascular disorders in patients with bipolar illness, including all of the elements of the metabolic syndrome, which is characterized by any three of the five following factors: increased waist circumference, glucose elevation or insulin intolerance, elevated triglycerides, increased cholesterol, and elevated blood pressure.
Some 60-80% of patients with bipolar illness are current or former smokers, and this is a far higher percentage than the rest of the general population. Therefore, all the increased cardiovascular risk that comes with smoking may be additive to a panoply of other factors noted above.
In addition, there appear to be many other mechanisms of increased risk including that derived from depression-related increases in inflammatory cytokines, increases in glucocorticoids, and decreases in neuroprotective factors such as interleukin 10 and BDNF. Increased stiffness of the inner wall (intima) of arteries has also been reported in association with the affective disorders, as well as increased stickiness of platelets.
Clinical Implications
Taken together, the above data suggest that there must be increased vigilance to the presence of the metabolic syndrome and other risk factors for cardiovascular disease in patients with bipolar illness; active treatment and prevention of these conditions should be routine. Moreover, in those at high risk, very active and aggressive treatment of these medical risk factors should be pursued, including attempts at encouraging smoking cessation. One of the more disturbing factors is a lack of adequate health care access in many patients with bipolar disorder and, in these instances, it would appear appropriate and necessary for the treating psychiatrist to provide some of the medical evaluation and treatment including lipid and blood pressure-lowering drugs where indicated.
Another major clinical implication of these data is the need for careful choice of medications in patients who are already at increased risk for medical comorbidities in order not to further increase these factors as a result of pharmacological treatment wherever possible. Thus, long-term tolerability and lack of effects on metabolic indices needs to be factored into efficacy considerations in arriving at the most appropriate risk/benefit evaluation for each individual patient.
There appears to be a substantial gradation in difference among the atypical antipsychotics in their potential for increasing metabolic and cardiovascular risks. Disappointingly, one of the most effective treatment agents, clozapine (Clozaril), is a major offender for weight gain, and the same is the case for olanzapine (Zyprexa), which can cause substantial increases in weight as well as increases in cholesterol and triglycerides.
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