Blood pressure monitoring

The publication of the CAFE study, which showed that significant drug effects, detected through noninvasive central blood pressure assessment, were not detected by brachial blood pressure measurements, signaled a new era in scientific research, pharmaceutical trials, and patient management.

With noninvasive central blood pressure monitoring, we can now determine the central blood pressure routinely in the clinical setting, offering a new level of understanding of how disease processes and drug therapies affect the blood pressure actually experienced by the heart, brain and kidneys.

Elevated central blood pressure – the pressure at the ascending aorta – can be caused by arterial stiffening or by reductions in heart rate. In both cases reflected blood pressure waves, which would otherwise return to the aorta during diastole, return early, during systole, increasing the pressure the heart pumps against. The recently published Strong Heart Study, a longitudinal study of native Americans sponsored by the NIH, identified elevated central pressure as a superior predictor of cardiovascular events, using noninvasive central blood pressure monitoring.

For pharmaceutical companies, the ability to non-invasively assess the effects of central blood pressure in clinical trial subjects is critically important:

• It may help identify and explain beneficial effects of cardiovascular drugs, which are not evident by measuring brachial blood pressure alone
• It may allow identification – and mitigation – of a drug’s central pressure, elevating effects in certain patients
• It may help to differentiate competing drug compounds in development
• It may help identify study volunteers who are at higher risk for cardiovascular events

In our practice and research, we see many elderly patients with isolated systolic hypertension, where elevated central pressure is normally the result of arterial stiffening due to age or arterial disease. We also see a number of young people who have elevated brachial pressure, once thought to be a largely benign condition because of their young age. However, it was not until we assessed central pressures in these individuals and found them to be elevated, that we realized that increased blood pressure in youth is also a potentially serious condition, requiring detailed follow-up and probably therapeutic intervention. In both cases, noninvasive central pressure monitoring is an valuable tool in assessing the patient’s hemodynamics and in making the right treatment decisions.

For pharmaceutical companies, an in-depth understanding of the effect of their products on arterial hemodynamics is critically important. Compounds that slow heart rate, or have a vasoconstricting effect, or even those that may provoke an inflammatory response in some patients may produce an increase central blood pressure, which would be of particular concern in medications used to treat chronic conditions in patient populations at high cardiovascular risk.

Many studies have demonstrated that elevated central blood pressure, which we now recognize as a vitally important physiological parameter, cannot be reliably estimated by measuring brachial blood pressure in individual patients. In research, drug development, and in patient care, routinely assessing central pressure is becoming a necessity.

BIOS

Dr Ian Wilkinson is a British Heart Foundation Senior Clinical Fellow in the Clinical Pharmacology Unit, Addenbrooke’s Hospital, Cambridge UK. He is also a Consultant Physician within Addenbrooke’s Hospital, specializing in the treatment of hypertension. His academic interests centre on the mechanisms underlying arterial stiffening and how a better understanding of these processes might lead to the development of novel therapies. Dr Wilkinson has also spoken widely on arterial stiffness and has led a number of phase I and II studies focusing on the therapeutic modulation of arterial stiffness.

Dr Carmel McEniery is a British Heart Foundation Intermediate Research Fellow, also based in the Clinical Pharmacology Unit in Cambridge. Her research interests focus on the role of the vascular endothelium in regulating arterial stiffness and on discovering more about the mechanisms leading to the development of hypertension in young individuals. She has also directed courses for academics and the pharmaceutical industry concerning the use of surrogate markers of cardiovascular disease, such as arterial stiffness and endothelial function, in the development of new cardiovascular drugs.

Contact: Doug Kurschinski, VP Market Development, AtCor Medical, Inc.
d.kurschinski@atcormedical.com Tel 001 630 799 8215