Lewis A. Lipsitz, M.D.

617-971-5318
lipsitz@hsl.harvard.edu

Education

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Research Interests and Teaching Activities

Dr. Lipsitz's research has focused on abnormal blood pressure regulation and its relationship to the development of falls and syncope in the elderly.  His initial prospective clinical investigations led to the recognition that nearly one third of syncopal episodes in frail elderly patients are related to hypotensive responses to common daily stresses such as posture change, meals, and preload reducing medications.  He was the first to identify postprandial hypotension in the elderly, probe its underlying mechanisms, and demonstrate its relationship to syncope. In randomized, double blind, placebo controlled trials he found that 3,4 DL threo dihydroxy phenylserine was an effective treatment, but caffeine was not.

In several elderly populations, Dr. Lipsitz observed a relationship between systolic hypertension and the susceptibility to hypotension. He found that both orthostatic and postprandial hypotension are related to supine BP elevation, independent of medication use. This may be due to the additive adverse effects of age and systolic hypertension on baroreflex function and diastolic ventricular filling. In a randomized, double blind, cross over trial he showed that treatment of BP elevation with a calcium channel blocker, ameliorated postprandial hypotension.  More recently he has shown that the treatment of hypertension increases cerebral blood flow in elderly hypertensive patients. His current work examines the relation between hypertension or other cardiovascular risk factors and frontal subcortical symptoms such as executive dysfunction, slow gait, depression, and urinary incontinence, and whether this relationship is due to cerebral hypoperfusion and resultant microvascular disease.

Building upon his observations that physiological measures such as blood pressure and heart rate are highly variable with beat to beat fluctuations that resemble nonlinear dynamical processes, Dr. Lipsitz applied the principles of nonlinear dynamics to his work.  He proposed that healthy physiologic function is characterized by the nonlinear interaction of multiple control processes and feedback loops that produce highly complex outputs  such as the beat to beat irregularity of the normal sinus cardiac rhythm, or the moment to moment adjustments in center of pressure during quiet standing.  Using a variety of mathematical techniques derived from Fourier analysis and chaos theory, he found that heart rate irregularity increases as neonatal swine develop innervation from the right stellate ganglion to the heart, and that the development of complex heart rate dynamics is prevented by right stellate ganglionectomy.  In healthy humans he reported degradation in the fractal structure of the sinus rhythm heart rate with advancing age. He also showed that women have greater and more irregular heart rate variability than men, possibly due to an effect of estrogen on beat to beat cardiovascular dynamics. These studies suggest that loss of integrated physiologic control associated with immaturity, male gender, or senescence may impair adaptive responses, and predispose individuals with these characteristics to injury or disease.

Using similar approaches, Dr. Lipsitz has shown specific alterations in heart rate, blood pressure, and respiratory dynamics preceding the onset of vasovagal syncope.   Furthermore, he has characterized abnormalities in the dynamics of postural sway in elders at risk of falls. These studies not only provide new insights into potential neural mechanisms of falls and syncope in the elderly, but also new diagnostic tools and therapeutic strategies to help identify and treat individuals at risk. One promising therapeutic intervention to prevent falls in the elderly is based on the physical principal of stochastic resonance, in which noise is used to enhance the detection of a weak signal. He has shown that mechanical noise delivered to the feet using vibratory insoles, can improve postural control and gait in groups of elderly people and patients with strokes, diabetic neuropathy, or falls.

Keywords

Falls, syncope, blood pressure, hypertension, nonlinear dynamics, cerebral blood flow, autoregulation

Selected Publications

1. Barnett SR, Morin RJ, Kiely DK, Gagnon M, Azhar G, Knight EL, Nelson JC, Lipsitz LA. Effects of age and gender on autonomic control of blood pressure dynamics. Hypertension 1999;33:1195-1200.
2. Ooi WL, Hossain M, Lipsitz LA. The association between orthostatic hypotension and recurrent falls in nursing home residents. Am J Med 2000;108:106-111.
3. Lipsitz LA, Mukai S, Hamner J, Gagnon M, Babikian V. Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke 2000;31:1897-1903.
4. Oberman AS, Gagnon MM, Kiely DK, Nelson JC, Lipsitz LA. Autonomic and neurohumoral control of postprandial blood pressure in healthy aging. J Gerontology 2000; 55(8): M477-M483.
5. Gambassi G, Lapane K, Sgaari A, Carbonon P, Gastsonis C, Lipsitz LA, Mor V, Bernabei R. Effects of angiotensin-converting enzyme inhibitors and digoxin on health outcomes of very old patients with heart failure. Arch Int Med 2000;160:53-60.
6. Narayanan K, Collins JJ, Hamner J, Mukai S, Lipsitz LA. Predicting the cerebral blood flow response to orthostatic stress: effects of age on the pressure-flow impulse response function. Am J Physiol 2001; 281:R716-R722.
7. Hunt BE, Taylor A, Hamner JW, Gagnon M, Lipsitz LA. Estrogen replacement therapy improves baroreflex regulation of vascular sympathetic outflow in postmenopausal women. Circulation 2001; 103(24): 2904-2914.
8. Hossain M, Ooi WL, Lipsitz LA. Intra-individual postural blood pressure variability and stroke in elderly nursing home residents. J Clin Epi 2001; 54:488-494.
9. Liu W, Collins JJ, Montero-Odasso M, Bean J, Kerrigan C, Lipsitz LA. Noise-enhanced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy. Arch Phys Med Rehab 2001 83:171-176.
10. Pugh KG, Lipsitz LA. The microvascular frontal-subcortical syndrome of aging. Neurobiology of Aging, 2002; 23:421-431.
11. Olufsen MS, Nadim A, Lipsitz LA. Dynamics of cerebral blood flow regulation explained using a lumped parameter model. Am J Physiol Integr Comp Physiol 2002; 282(2): R611-622.
12. Lipsitz LA. The dynamics of stability: the physiologic basis of functional health and frailty. J Gerontol Biol Sci 2002; 282:R6ll-R622.
13. Dhruv NT, Miemi JB, Harry JD, Lipsitz LA,Collins JJ. Ehancing tactile sensation in older adults with electrical noise stimulation. NeuroReport 2002; 13(5): 597-600.
14. Gravelle DC, Laughton CA, Dhruv NT, Katdare KD, Niemi JF, Lipsitz LA, Collins JJ. Noise-enhanced balance control in older adults. NeuroReport 2002;13(15):1853-1856.
15. Priplata AA, Niemi JB, Harry JD, Lipsitz LA, Collins JJ. Enhancing elderly balance control with vibrating insoles. Lancet 2003; 362:1123-1124.
16. Priplata A, Niemi J, Salen M, Harry J, Lipsitz LA, Collins JJ. Noise-enhanced human balance control. Phys Rev Letters 2003; 89(23): 238101.
17. Mukai S, Gagnon M, Iliputaife I, Hamner JW, Lipsitz LA. Effect of systolic blood pressure and carotid stiffness on baroreflex gain in elderly subjects. J Gerontol 2003; 58A(7): 626-630.
18. Kuo H-K, Sorond F, Milberg W, Lipsitz LA. Effect of blood pressure on cognitive functions in the elderly. J. Gerontol: Medical Sciences 2004; 11:1191-94.
19. Hamner JW, Cohen MA, Mukai S, Lipsitz LA, Taylor JA. Spectral indices of cerebral blood flow control: responses to augmented blood pressure oscillations. J Physiol 2004; 559(3): 965-973.
20. Serrador JM, Sorond FA, Vyas M, Gagnon M, Iloputaife ID, Lipsitz LA. Cerebral pressure-flow relations in hypertensive elderly humans: transfer gain in different frequency domains. J Appl Physiol 2005; 98:151-9.
21. Amaral L, Diaz-Guilera A, Moreira A, Goldberger A, Lipsitz L. Emergence of complex dynamics in a simple model of signaling networks. Proc Natl Acad Sci 2004; 101(44): 15551-15555.
22. Lipsitz LA, Gagnon M, Vyas M, Iloputaife I, Kiely DK, Sorond F, Serrador J, Cheng DM, Babikian V, Cupples LA. Antihypertensive therapy increases cerebral blood flow and carotid distensibility in hypertensive elderly subjects. Hypertension 2005; 45:216-221.
23. Novak V, Yang ACC, Lepicovsky L, Goldberger AL, Lipsitz LA, Peng C-K. Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension. BioMedical Engineering On-Line 2004; 3(1):39.
24. Sorond FA, Serrador J, Khavari R, Lipsitz LA. Regional cerebral autoregulation during orthostatic stress: age-related differences. J Gerontol Med Sci 2005; 60A: 1484-87.
25. Olufsen MS, Ottesen JT, Tran HT, Ellwein LM, Lipsitz LA, Novak V. Blood pressure and blood flow variation during postural change from sitting to standing: Model development and validation. J Applied Physiol 2005; 99:1523-37.
26. Sorond FA, Schnyer DM, Serrador JM, Milberg WP, Lipsitz LA. Cerebral Blood Flow Regulation During Cognitive Tasks: Effects of Healthy Aging. Cortex 44. 2008; 179-184.
27. Lipsitz LA, Iloputaife I, Gagnon M, Kiely DK, Serrador JM.Enhanced Vasoreactivity and Its Response to Antihypertensive Therapy in Hypertensive Elderly Women. Hypertension 2006; 47:377-383.
28. Novak V, Hu K, Vyas M, Lipsitz LA. Cardiolocomotor Coupling in Young and Elderly People. J. of Gerontol Med Sci 2007, Vol. 62A, No. 1, 86-92.
29. Costa M, Priplata A, Lipsitz LA, Wu Z, Huang NE, Goldberger AL, Peng CK. Noise and poise: enhancement of postural complexity in the elderly with a stochastic resonance- based therapy. Eur Phys Letters 2007; 77: 68008.1-68008.5.
30. Hajjar I., Lackland DT, Cupples A, Lipsitz LA. Association Between Concurrent and Remote Blood Pressure and Disability in Older Adults. Hypertension. 2007;50: 1026-1032.
31. Leveille SG, Kiel DP, Jones RN, Roman A, Hannon MT, Dorond FA, Kang HG, Samelson EJ, Gagnon M, Freeman M, Lipsitz L. The MOBILIZE Boston Study: Design and methods of a prospective cohort study of novel risk factors for falls in an older population. BMC Geriatrics 2008; 8: 16.
32. Lipsitz LA. Dynamic models for the study of frailty. Mech Ageing Dev 2008, 129: 675-676.
33. Galica, AM, Kang HG, Priplata AA, D'Andrea SE, Starobinets OV, Sorond FA, Cupples LA, Lipsitz LA, Subsensory Vibrations to the Feet Reduce Gait Variability in Elderly Fallers. Gait & Posture, 2009, 30: 383-387.