A large case-control study suggests that calcium channel blockers are the only antihypertensives that reduce the risk for Parkinson disease.
For the past decade, the potential of antihypertensive agents to affect the incidence of Parkinson disease (PD) has been evaluated by various methodologies, yielding a confusing array of conclusions. Now, researchers have conducted a careful case-control study of incident PD diagnosis and its association with various antihypertensives. They identified 3637 patients with incident PD and 3637 well-matched controls from the U.K.-based General Practice Research Database, which contained at least 3 years of data before the index (diagnosis) date for each participant. The authors separately analyzed four major classes of antihypertensive drugs: angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II antagonists, and beta-blockers.
Use of calcium channel blockers — but not of the other antihypertensive classes — was associated with a significantly reduced risk for PD (odds ratio, 0.77). Risk reductions with this drug class were even greater with prolonged use and in people aged 80 or older. Use of beta-blockers for reasons other than cardiovascular disease or hypertension was associated with increased PD incidence. The authors attribute this association to the presence of symptoms such as tremor that often prompted the beta-blocker use and may have been parkinsonian manifestations.
Although the authors do not discuss in any detail the mechanisms by which calcium channel blockers might be beneficial in Parkinson disease, the importance of calcium ions in various major neuronal functions supports a role in altering the natural history of this disorder. Aging and disease-related stressors (e.g., accumulation of reactive oxygen species or of disease-related proteins such as alpha-synuclein) can impair calcium homeostasis, thereby disrupting neuronal functions and accelerating the appearance of parkinsonian symptoms. A recent animal study demonstrated that increased reliance on calcium and increased susceptibility to stressors in aged dopaminergic neurons could be reversed by calcium channel blockers, allowing cells to use a healthier form of cellular homeostasis more typical of juvenile cells. Do these data suggest that calcium channel blockers could emerge as a neuroprotective therapy for PD? Relevant clinical research is being planned, so the answer to this important question may be only a few years away.
People taking calcium channel blockers to control their high blood pressure may find the regimen has a double benefit: Researchers say long-term use of the drugs also might cut the risk of developing Parkinson's disease.
But the findings are far from definitive and not yet ready for prime-time medical practice.
"There are not necessarily direct clinical implications, but the data support previous hypotheses that calcium channel blockers may have neuro-protective effects," said study senior author Christoph R. Meier, a clinical pharmacologist with the University Hospital Basel, in Switzerland. "This may stimulate additional clinical and mainly basic research in this area."
The findings were published in the Feb. 6 online issue of Neurology, the medical journey of the American Academy of Neurology.
Parkinson's disease is a chronic, degenerative neurological disorder affecting at least one million people in the United States and 6 million people worldwide, according to the Michael J. Fox Foundation for Parkinson's Research. The condition involves the loss of brain cells that produce the chemical dopamine, resulting in movement problems including tremors.
Previous studies with rodents and primates had uncovered a possible "neuroprotective effect" from calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors, another class of blood pressure medications, the researchers said.
The new study looked at the effect of calcium channel blockers, Ace inhibitors, ATII antagonists and beta blockers on the development of Parkinson's disease.
The study involved more than 7,000 men and women in the United Kingdom over the age of 40, half of whom had been diagnosed with Parkinson's than half of whom had not. Almost half the people in each group used blood pressure medications.
Participants currently taking calcium channel blockers lowered their risk of developing Parkinson's by 23 percent. There was no real effect for the other type of medications.
The strongest reduction in risk was seen in patients who had had 30 or more prescriptions filled and were still receiving prescriptions within 90 days prior to the diagnosis of Parkinson's, the researchers said.
Women tended to have more of a risk reduction than men but not if they had less than 30 prescriptions filled.
Individuals over the age of 80 had the most pronounced lowering of risk.
But even the study authors acknowledged that it's not clear where to go next with the findings.
"It may be desirable that basic research activities explore the effect of calcium channel blockers on the central nervous system which may lead (in theory to new therapeutic stragies or even new drugs to prevent or treat Parkinson's," Meier said." Regarding clinical or epidemiological/observational research, it would be nice if other research groups analyzed their databases and came up with their findings. They may either confirm our observations or come to the conclusion that our finding is isolated and that there is no need to further pursue this issue."
Dr. Ralph Sacco, professor and chair of neurology at the University of Miami Miller school of medicine, agreed. "This is a tricky one. You don't know if there is a true association are not. There are potential problems with this type of analysis," he said.
But Sacco pointed out, there is evidence accumulating on the relationship between Alzheimer's, another neurodegenerative disease, and circulatory system problems.