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High resting heart rate portends cognitive decline

AMSTERDAM – A high resting heart rate proved to be a strong and independent predictor of cognitive decline within the next 4 years in a study of nearly 28,000 patients at high cardiovascular risk.

The clinical implications of this finding, however, remain unclear, according to Dr. Darryl P. Leong.

"What this study cannot answer, and which must be answered, is whether resting heart rate is just a marker of the risk of cognitive decline or whether it exists in the causal pathway. Further research is needed to determine if resting heart rate represents a therapeutic target to prevent cognitive decline. I think the only way to test this is with some intervention to reduce heart rate – whether using a beta-blocker or a medication such as ivabradine – to see whether or not it influences the incidence of cognitive decline," he said in presenting the study findings at the annual congress of the European Society of Cardiology.

"Cognitive dysfunction and decline, I think, are going to be a major scourge over the next decades," he added in explaining the study rationale. "We have an increasingly aged population, we have increasingly better treatment and survival of cardiovascular disease, and as a result more and more people are going to be living long enough to experience the misfortune of having cognitive impairment," said Dr. Leong, a postdoctoral fellow at the population health research institute at McMaster University, Hamilton, Ont.

He presented a post hoc analysis of two major randomized clinical trials – ONTARGET (the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in Angiotension-Converting Enzyme Inhibitor–Intolerant Subjects With Cardiovascular Disease). In these two trials, patients with diabetes or vascular disease were assigned to ramipril, telmisartan, both, or placebo. The primary outcomes have already been published. Dr. Leong and his coinvestigators at McMaster used the database for the two trials, which contains information on baseline resting heart rate and subsequent cognitive decline in 27,660 participants.

The quartiles of baseline resting heart rate were less than 60 bpm, 60-66, 67-74, and 75 or more bpm. Cognitive decline was defined as at least a 3-point drop from baseline on the Mini-Mental State Exam at a median 4 years of follow-up.

During the follow-up period, 17% of the 27,660 patients exhibited cognitive decline. The investigators noted a stepwise relationship between baseline resting heart rate and cognitive deterioration: Those in the top two quartiles – that is, patients with a resting heart rate of 67 bpm or more – had a 16% greater risk than did those in the lower two quartiles. This was the case even after extensive adjustment in a multivariate regression analysis controlled for baseline demographic variables, cardiovascular comorbidities, depressive symptoms, blood pressure, dietary habits, renal function, medications, lipid levels, left ventricular hypertrophy, alcohol consumption, and physical activity level.

Even after investigators controlled for baseline use of beta-blockers, calcium channel blockers, and digoxin, resting heart rate remained predictive of subsequent cognitive decline, according to Dr. Leong.

He reported having no relevant financial conflicts.

[email protected]

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AMSTERDAM – A high resting heart rate proved to be a strong and independent predictor of cognitive decline within the next 4 years in a study of nearly 28,000 patients at high cardiovascular risk.

The clinical implications of this finding, however, remain unclear, according to Dr. Darryl P. Leong.

"What this study cannot answer, and which must be answered, is whether resting heart rate is just a marker of the risk of cognitive decline or whether it exists in the causal pathway. Further research is needed to determine if resting heart rate represents a therapeutic target to prevent cognitive decline. I think the only way to test this is with some intervention to reduce heart rate – whether using a beta-blocker or a medication such as ivabradine – to see whether or not it influences the incidence of cognitive decline," he said in presenting the study findings at the annual congress of the European Society of Cardiology.

"Cognitive dysfunction and decline, I think, are going to be a major scourge over the next decades," he added in explaining the study rationale. "We have an increasingly aged population, we have increasingly better treatment and survival of cardiovascular disease, and as a result more and more people are going to be living long enough to experience the misfortune of having cognitive impairment," said Dr. Leong, a postdoctoral fellow at the population health research institute at McMaster University, Hamilton, Ont.

He presented a post hoc analysis of two major randomized clinical trials – ONTARGET (the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in Angiotension-Converting Enzyme Inhibitor–Intolerant Subjects With Cardiovascular Disease). In these two trials, patients with diabetes or vascular disease were assigned to ramipril, telmisartan, both, or placebo. The primary outcomes have already been published. Dr. Leong and his coinvestigators at McMaster used the database for the two trials, which contains information on baseline resting heart rate and subsequent cognitive decline in 27,660 participants.

The quartiles of baseline resting heart rate were less than 60 bpm, 60-66, 67-74, and 75 or more bpm. Cognitive decline was defined as at least a 3-point drop from baseline on the Mini-Mental State Exam at a median 4 years of follow-up.

During the follow-up period, 17% of the 27,660 patients exhibited cognitive decline. The investigators noted a stepwise relationship between baseline resting heart rate and cognitive deterioration: Those in the top two quartiles – that is, patients with a resting heart rate of 67 bpm or more – had a 16% greater risk than did those in the lower two quartiles. This was the case even after extensive adjustment in a multivariate regression analysis controlled for baseline demographic variables, cardiovascular comorbidities, depressive symptoms, blood pressure, dietary habits, renal function, medications, lipid levels, left ventricular hypertrophy, alcohol consumption, and physical activity level.

Even after investigators controlled for baseline use of beta-blockers, calcium channel blockers, and digoxin, resting heart rate remained predictive of subsequent cognitive decline, according to Dr. Leong.

He reported having no relevant financial conflicts.

[email protected]

AMSTERDAM – A high resting heart rate proved to be a strong and independent predictor of cognitive decline within the next 4 years in a study of nearly 28,000 patients at high cardiovascular risk.

The clinical implications of this finding, however, remain unclear, according to Dr. Darryl P. Leong.

"What this study cannot answer, and which must be answered, is whether resting heart rate is just a marker of the risk of cognitive decline or whether it exists in the causal pathway. Further research is needed to determine if resting heart rate represents a therapeutic target to prevent cognitive decline. I think the only way to test this is with some intervention to reduce heart rate – whether using a beta-blocker or a medication such as ivabradine – to see whether or not it influences the incidence of cognitive decline," he said in presenting the study findings at the annual congress of the European Society of Cardiology.

"Cognitive dysfunction and decline, I think, are going to be a major scourge over the next decades," he added in explaining the study rationale. "We have an increasingly aged population, we have increasingly better treatment and survival of cardiovascular disease, and as a result more and more people are going to be living long enough to experience the misfortune of having cognitive impairment," said Dr. Leong, a postdoctoral fellow at the population health research institute at McMaster University, Hamilton, Ont.

He presented a post hoc analysis of two major randomized clinical trials – ONTARGET (the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in Angiotension-Converting Enzyme Inhibitor–Intolerant Subjects With Cardiovascular Disease). In these two trials, patients with diabetes or vascular disease were assigned to ramipril, telmisartan, both, or placebo. The primary outcomes have already been published. Dr. Leong and his coinvestigators at McMaster used the database for the two trials, which contains information on baseline resting heart rate and subsequent cognitive decline in 27,660 participants.

The quartiles of baseline resting heart rate were less than 60 bpm, 60-66, 67-74, and 75 or more bpm. Cognitive decline was defined as at least a 3-point drop from baseline on the Mini-Mental State Exam at a median 4 years of follow-up.

During the follow-up period, 17% of the 27,660 patients exhibited cognitive decline. The investigators noted a stepwise relationship between baseline resting heart rate and cognitive deterioration: Those in the top two quartiles – that is, patients with a resting heart rate of 67 bpm or more – had a 16% greater risk than did those in the lower two quartiles. This was the case even after extensive adjustment in a multivariate regression analysis controlled for baseline demographic variables, cardiovascular comorbidities, depressive symptoms, blood pressure, dietary habits, renal function, medications, lipid levels, left ventricular hypertrophy, alcohol consumption, and physical activity level.

Even after investigators controlled for baseline use of beta-blockers, calcium channel blockers, and digoxin, resting heart rate remained predictive of subsequent cognitive decline, according to Dr. Leong.

He reported having no relevant financial conflicts.

[email protected]

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AT THE ESC CONGRESS 2013

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Major finding: Individuals at high cardiovascular risk who had a baseline resting heart rate of 67 bpm or more had a 16% greater risk of clinically meaningful cognitive decline during the next 4 years than did those with a resting heart rate below that threshold.

Data source: A post hoc secondary analysis of data on the nearly 28,000 participants in the randomized, double-blind ONTARGET and TRANSCEND clinical trials.

Disclosures: The post hoc analysis was funded by the population health research institute at McMaster University. The presenter reported having no relevant financial conflicts.