• Users Online: 21
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
VIEW POINT
Year : 2017  |  Volume : 6  |  Issue : 2  |  Page : 73-77

Risk assessment, risk management, and prevention of acute vascular events


Department of Laboratory Medicine and Pathology, Thrombosis Research, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA

Date of Web Publication31-Mar-2017

Correspondence Address:
Gundu H R Rao
Thrombosis Research, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2250-3528.203529

Rights and Permissions
  Abstract 

South Asians have a very high incidence of cardiometabolic diseases such as hypertension, central abdominal obesity, metabolic syndrome, type 2 diabetes, heart disease, and stroke. In spite of the fact that common risk factors associated with these clinical conditions are known, we do not have point-of-care assays, to monitor the disease of the vessels, and the efficacy of antiplatelet therapy. We have a window of opportunity to develop three-dimensional ultrasound methodologies, to monitor the subclinical atherosclerosis, altered flow velocities of regional vascular beds, as well as plaque progression and regression in the major vessels. We also have opportunities to develop state-of-the-art methodologies for monitoring the efficacy or otherwise of antiplatelet therapies. In this overview, we share our views and strategies for the development of affordable medical technologies in India, for monitoring vessel wall pathology as well as for better management of antiplatelet therapies.

Keywords: Cardiovascular diseases, primary prevention, risk assessment, risk management


How to cite this article:
Rao GH. Risk assessment, risk management, and prevention of acute vascular events. J Clin Prev Cardiol 2017;6:73-7

How to cite this URL:
Rao GH. Risk assessment, risk management, and prevention of acute vascular events. J Clin Prev Cardiol [serial online] 2017 [cited 2020 Nov 26];6:73-7. Available from: https://www.jcpconline.org/text.asp?2017/6/2/73/203529




  Introduction Top


Since the time Framingham studies developed the risk assessment and risk management strategies, there is a great emphasis on the management of observed risks for prevention of acute cardio- and cerebrovascular events.[1],[2],[3],[4] In view of these observations, Pharma companies are developing various drugs, to manage the well-characterized risk factors such as inflammation, vascular dysfunction, hypertension, obesity, lipid abnormalities, and platelet and coagulation hyperfunctions.[5],[6],[7] A few years ago, there was a debate about the possibilities for better management of these chronic diseases. Cohn et al. at the University of Minnesota advocated the management of disease of the vessels, rather than the management of risk factors that promote these diseases. They developed a 10-point diagnostic screening algorithm, to monitor the progress and regression of the disease.[8],[9],[10] Whereas the researchers at the Robarts Laboratory, Ontario, Canada, developed a three-dimensional (3D) ultrasound methodology, to follow the progression and regression of carotid artery plaques and showed the efficacy of this methodology for monitoring statin therapy as well as beneficial effects of lifestyle changes.[11],[12],[13] On the other hand, Belcaro et al. in England developed proprietary software and algorithms, to assess the altered morphology of carotid and femoral bifurcations, to predict the progress of subclinical atherosclerosis.[14],[15],[16] Of the various risk factors associated with the pathogenesis of acute vascular events, in our opinion, the progression of vessel wall disease, narrowing of the vessels, stiffening of the vessel walls, and the thrombotic state of the blood plays a critical role in developing acute vascular events. In view of these observations, we at the University of Minnesota developed and validated a point-of-care device, to monitor platelet-activation-dependent facilitation of clot formation.[17] This device used a stainless steel coil placed in the midsection of a capillary, to induce shear-mediated activation of platelets, which resulted in the promotion of clot formation in circulating blood. Just like the 3D ultrasound technology of Robarts laboratory, and the proprietary software and analytics of Professor Andrew Nicolaides, platelet reaction time monitor is also not available worldwide for clinical applications. In this overview, we will share with you our collective ideas as to how we can develop indigenous affordable medical technologies, to monitor the progression of vessel wall disease as well as antiplatelet therapies.


  Monitoring Vascular Physiology and Pathology Top


Alterations in the vessel wall physiology and compliance of the vessels and the changes if any, in the blood flow velocity, are the earliest stages of vascular dysfunction that could be detected.[18],[19],[20],[21],[22] There are several devices available in the market that can monitor changes in the flow velocity and provide information on endothelial dysfunction. Some of the devices in use include CVProfilor (Hypertension Diagnostics, USA: Hypertensiondiagnostics.com), Periscope (Genesis Medical System, Hyderabad, India: Genesismedicals.com), and TM-Oxi (LD Technologies, Florida: www.ldteck.com). Majority of the people who suffer heart attacks have no symptoms, making prevention very difficult. However, now with the availability of these devices, we will be able to identify heart disease (vessel wall disease or dysfunction) at its earliest stage in people with no symptoms. In spite of the advances made in the diagnostic medical device development, we still do not have a simple hand-held, point-of-care monitor for diagnosis and management of vascular dysfunction.

Hypertension diagnostics (www.hypertensiondiagnostics.com) of Minneapolis, Minnesota, has developed a method for noninvasively measuring the elasticity of large and small arteries, of which small artery elasticity is the earliest and most sensitive marker for cardiovascular (CV) disease. One of the tests that the University of Minnesota uses in their 10-point risk assessment is CVProfilor. The device collects 30 s of blood pressure waveform data from a small artery and a large one, performs analysis of the digitized blood pressure waveforms and generates a report that contains information on the blood pressure, body surface area, body mass index, and both C-1 large and C-2 small artery elasticity indices. According to the researchers who have used this device, changes in the small artery elasticity have been highly predictive of CV disease.[23] Its main product CV Profilor, Hypertension Diagnostics, Minneapolis, MN has been approved by the US Food and Drug Administration.

Genesis Medical Systems of Hyderabad (www.genesismedicals.com), India, have developed a simple noninvasive oscillometric device (Periscope), to monitor pulse wave velocity (PWV) in small arteries. The report generated by this system provides 8-second tracings of electrocardiography, all pressure pulse waveforms, and calculated results. PWV is the speed at which the blood pressure pulses travel from the heart to the peripheral artery after the blood rushes out during contraction. This measurement is used for evaluating arterial stiffness. PWV increases with stiffness of the arteries. The PWV is considered one of the most important clinical parameters for evaluating CV risk, and therapeutic efficacy.[24] The commercial devices dedicated to PWV measurements estimate a regional assessment, measured between two vessels. However, we feel that a local measurement or regional measurement is more precise for evaluation of the health of the vessels. Peripheral arteries are stiffer than the deeper arteries. The heterogeneity of the structure of arterials wall and its components pose challenge for PWV measurements and computations.

Ultrasonography has been used extensively as a diagnostic imaging modality. Dr. Aaron Fenster et al. at Robarts Research Institute, London, Canada, have developed 3D ultrasound imaging for improving the visualization and quantification of atherosclerotic plaque in the carotid artery [Figure 1].[11],[12],[13]
Figure 1: Three-dimensional view of carotid artery (Courtesy: Dr. Aaron Fenster)

Click here to view


This technology if available worldwide will be of great help in monitoring the morphology, volume of the plaque, and for the assessment of therapeutic efficacy. There are several types of ultrasound systems for obtaining 3D images. The commonly used options are the mechanical linear 3D ultrasound scanning and the sensed free-hand techniques. A 10-year follow-up study by Nicolides et al. on carotid and femoral bifurcation ultrasound screening demonstrated the usefulness of this simple technique in identifying populations with varying degree of risks for CV events, depending on the progression of arteriosclerotic vascular disease. They were able to classify those with low risk, limited risk, moderate risk and high risk, based on carotid and femoral bifurcation morphology.[16]

As we mentioned earlier, B-mode ultrasound is in use for several years as a convenient, safe diagnostic tool. This method has been extensively used for monitoring carotid and femoral bifurcation morphology, to detect subclinical atherosclerosis, plaque volume, plaque morphology, plaque texture, obstruction of the arteries (arterial sonography), venous thrombosis (thrombosonography), venous insufficiency (venosonography), progression of the plaque volume, and response to therapies.[13],[16] We have discussed with major manufacturers of ultrasound equipment (Fujifilm Holdings, GE Healthcare, Siemens Healthcare, Phillips Healthcare, Shimadzu Corporation, Toshiba Medical Systems, Carestream Health and Hitachi Medical) the need for a hand-held device. Some of these manufactures already have high-end equipment capable of imaging peripheral arteries and veins. We the members of a Consortium for the development of affordable medical technologies, National Design Research Foundation (NDRF), Bangalore, India, are interested in developing a simple hand-held ultrasound imaging device, which can be interfaced with existing noninvasive diagnostic platforms such as RISC and TM-Oxi, with proprietary software and analytics, so that the imaging of the peripheral arteries and veins could be done at the clinics, to follow flow velocity alterations due to subclinical atherosclerosis or blocks.


  Aspirin Resistance Top


The role of platelets in the promotion of thrombus formation and growth leading to acute vascular events is well established. When it comes to antiplatelet therapies, aspirin and clopidogrel have been the drugs of choice. According to the National Commission on Macroeconomics and Health, 62 million people in India have coronary artery disease.[25] Even if half of these populations are on antiplatelet therapies, we will have close to 30 million people who are on aspirin or clopidogrel prophylaxis. Aspirin has been is use for several decades for prophylaxis. However, in recent years, there is considerable concern about subjects developing resistance for this drug. In our opinion, there is no such thing as aspirin resistance.[26],[27],[28],[29],[30] In our experience of four decades, we have never come across a patient whose platelet cyclooxygenase (COX) was not inhibited by oral aspirin. However, there seems to be some clinical evidence to suggest that those on aspirin therapy found to have increased urinary metabolites of thromboxane will be at higher risk for acute vascular events. Therefore, optimization of therapies would yield better results and greater protection, if we develop point-of-care assays to monitor the efficacy of these therapies. What are some of the options? Simplest would be to monitor platelet activation by the substrate arachidonic acid (AA) using a conventional aggregometry. One can also use flow cytometer and monitor activation of GP11b/111a receptor on platelets post, AA-mediated stimulation.[31]

Since aspirin is a specific inhibitor of COX enzymes, one can monitor the ability of platelets from patients undergoing aspirin prophylaxis to generate COX metabolites. One can assay for the final stable metabolite of thromboxane B2 in the plasma or the urinary metabolite of thromboxane (11-dehydro TXB2). Commercial Elisa kits are available for monitoring these metabolites in plasma and urine.[32],[33],[34] Since these kits have to be imported, the cost per assay is going to be quite high. One can develop these assay kits provided we develop the capability to produce TXB specific antibodies in India. Another alterative methodology will be to develop assay for urinary metabolites using gas chromatography/liquid chromatography-mass spectrometry. It is possible to develop all these methodologies. However, the limitations are the cost associated with the development of these technologies, creation of awareness among the clinicians, and effective marketing.


  Clopidogrel Resistance Top


Clopidogrel is a pro-drug and needs to be metabolized by the liver (P450) enzymes to generate active metabolites. There is considerable concern about the possible existence of clopidogrel resistance in the patient population. Similar to aspirin resistance, there is no real clopidogrel resistance. Having said that, we need to explain why certain people do not get the maximum protection from this kind of therapy. Not everyone has the same level of P450 activity. In addition, there seems to be some genetic heterogeneity in population as far as the function of this enzyme at the gene level. What are our options? We can monitor platelet response to adenosine diphosphate using conventional aggregometry. We can also monitor platelet function using flow cytometry and enzyme immunoassay that measure phosphorylation status of vasodilator phosphoprotein by aggregometry as well as by flow cytometry of P-selectin expression.[35],[36],[37]

Genetic polymorphisms of CYP2C19 modulate clopidogrel pharmacokinetics and pharmacodynamics in healthy volunteers, as well as in patients. As compared with subjects with no CYP2C19 variant allele, subjects carrying one or two CYP2C19 loss-of-function alleles have been shown to have lower plasma concentrations of the active metabolite of clopidogrel and a decrease in the antiplatelet effect of clopidogrel in ex vivo aggregation tests.[38] Results of several recent studies support and extend these findings from previous studies by showing a worse clinical outcome in patients carrying two CYP2C19 loss-of-function alleles who were treated with clopidogrel after acute myocardial infarction.[38],[39],[40],[41],[42],[43],[44]


  Detection of the Cyp Genotyping by Taqman Polymerase Chain Reaction Assay Top


SNPs of each gene can be genotyped by TaqMan assay on ABI 7300 Real-Time PCR System (Applied Bio systems, Foster City, CA) as described by Ota et al.: (Int. J Med. Sci. 12 (1) 2015 PMC 4278879. The TaqMan assays could be performed with a 20 μL reaction volume with 10 μL of thunderbird probe quantitative polymerase chain reaction (PCR) Mix (TOYOBO), 0.4 μL of 50 × ROX reference dye (TOYOBO), 1 μL of 20 × each TaqMan probe and each Primer Mix, 2 μL of 2 × PCR Buffer for KOD FX Neo (TOYOBO), and 6.6 μL of distilled water. The dried saliva on a sampler could be used for these assays for DNA extraction. The thermal cycling process could be performed according to the Applied Biosystems PCR conditions: 2 min at 50°C, 10 min at 95°C, forty cycles of denaturation at 95°C for 15s, and annealing and extension at 60°C for 1 min. The results could be analyzed by ABI Prism 7300 SDS software. Alternately, Clopidogrel and its active metabolite, clopidogrel carboxylic acid could be monitored in plasma using high-performance liquid chromatography/mass spectroscopy.[41] Determining the concentration of the active metabolite in the plasma will serve as a useful tool for monitoring the compliance as well as for determining the variability in the metabolism between the various subjects.

South Asians have very high incidence of cardiometabolic diseases, such as inflammation, vascular dysfunction, abdominal obesity, metabolic syndrome, Type-2 diabetes, heart disease and stroke.[45],[46],[47],[48] These chronic metabolic diseases by and large are due to alteration in vascular physiology and function. Therefore, development of cost-effective, noninvasive devices to monitor flow velocity and fluid dynamics of regional vascular beds will help us in early detection of vascular disease. We at the NDRF, Institution of Engineers, Bengaluru, are putting together a consortium of experts, to facilitate the development of affordable medical technologies. Once we have identified the experts and their field of expertise, we would encourage them to build prototypes of devices that can monitor flow velocity and morphology or peripheral arterial and venous circulation. Availability of such device and clinical data will be useful for developing proprietary software and analytical tools for risk assessment and monitoring of therapy.[49],[50] We at the University of Minnesota have been working on morphology, biochemistry, physiology and pharmacology of platelets for over four decades. We have developed extensive contacts in India with cardiac caregivers. We are in a very good position to develop specific point-of-care assays to monitor antiplatelet therapies.[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.  Back to cited text no. 1
    
2.
D'Agostino RB Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: The Framingham heart study. Circulation 2008;117:743-53.  Back to cited text no. 2
    
3.
D'Agostino RB Sr., Grundy S, Sullivan LM, Wilson P; CHD Risk Prediction Group. Validation of the Framingham coronary heart disease prediction scores: Results of a multiple ethnic groups investigation. JAMA 2001;286:180-7.  Back to cited text no. 3
    
4.
Conroy RM, Pyörälä K, Fitzgerald AP, Sans S, Menotti A, De Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: The SCORE project. Eur Heart J 2003;24:987-1003.  Back to cited text no. 4
    
5.
Rao GH. Handbook of Platelet Physiology and Pharmacology. Boston: Kluwer Academic Publishers; 1999.  Back to cited text no. 5
    
6.
Rao GH. Physiology and pharmacology of platelets. Int J Prog Cardiovasc Sci 1995;2:108-10.  Back to cited text no. 6
    
7.
Rao GH, Rao AT. Pharmacology of platelet activation-inhibitory drugs. Indian J Physiol Pharmacol 1994;38:69-84.  Back to cited text no. 7
    
8.
Cohn JN, Hoke L, Whitwam W, Sommers PA, Taylor AL, Duprez D, et al. Screening for early detection of cardiovascular disease in asymptomatic individuals. Am Heart J 2003;146:679-85.  Back to cited text no. 8
    
9.
Cohn JN, Duprez DA, Grandits GA. Arterial elasticity as part of a comprehensive assessment of cardiovascular risk and drug treatment. Hypertension 2005;46:217-20.  Back to cited text no. 9
    
10.
Duprez DA, Cohn JN. Identifying early cardiovascular disease to target candidates for treatment. J Clin Hypertens (Greenwich) 2008;10:226-31.  Back to cited text no. 10
    
11.
Fenster A, Lee D, Sherebrin S, Rankin R, Downey D. Three-dimensional ultrasound imaging of the vasculature. Ultrasonics 1998;36:629-33.  Back to cited text no. 11
    
12.
Landry A, Spence JD, Fenster A. Measurement of carotid plaque volume by 3-dimensional ultrasound. Stroke 2004;35:864-9.  Back to cited text no. 12
    
13.
Spence JD. Ultrasound measurement of atherosclerosis. Stroke 2004;35:e87-8.  Back to cited text no. 13
    
14.
Belcaro G, Nicolaides AN, Laurora G, Cesarone MR, De Sanctis M, Incandela L, et al. Ultrasound morphology classification of the arterial wall and cardiovascular events in a 6-year follow-up study. Arterioscler Thromb Vasc Biol 1996;16:851-6.  Back to cited text no. 14
    
15.
Griffin M, Nicolaides A, Tyllis T, Georgiou N, Martin RM, Bond D, et al. Carotid and femoral arterial wall changes and the prevalence of clinical cardiovascular disease. Vasc Med 2009;14:227-32.  Back to cited text no. 15
    
16.
Nicolides AN. Screening for cardiovascular risk. Br J Cardiol 2010;17:105-7.  Back to cited text no. 16
    
17.
Johnson GJ, Sharda AV, Rao GHR, Ereth MH, Laxson DD, Owen WG. Measurement of shear-activated platelet aggregate formation: Utility in evaluation of clopidogrel-and aspirin-induced platelet function inhibition. J Appl Clin Thromb Hemost 2012;18:140-9.  Back to cited text no. 17
    
18.
Maarek A, Gandhi PG, Rao GH. Identifying autonomic neuropathy and endothelial dysfunction in type-2 diabetic patients. EC Neurol 2015;2.2:63-78.  Back to cited text no. 18
    
19.
Hadi HA, Carr CS, Al Suwaidi J. Endothelial dysfunction: Cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag 2005;1:183-98.  Back to cited text no. 19
    
20.
Järvisalo MJ, Raitakari OT. Ultrasound assessment of endothelial function in children. Vasc Health Risk Manag 2005;1:227-33.  Back to cited text no. 20
    
21.
Frick M, Weidinger F. Endothelial function: A surrogate endpoint in cardiovascular studies? Curr Pharm Des 2007;13:1741-50.  Back to cited text no. 21
    
22.
Fichtlscherer S, Breuer S, Zeiher AM. Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes: Further evidence for the existence of the vulnerable patient. Circulation 2004;110:1926-32.  Back to cited text no. 22
    
23.
Cohn JN, Duprez DA. Time to foster a rational approach to preventing cardiovascular morbid events. J Am Coll Cardiol 2008;52:327-9.  Back to cited text no. 23
    
24.
Pereira T, Correia C, Cardoso J. Novel methods for pulse wave velocity measurement. J Med Biol Eng 2015;35:555-65.  Back to cited text no. 24
    
25.
Sekhri T, Kanwar RS, Wilfred R, Chugh P, Chhillar M, Aggarwal R, et al. Prevalence of risk factors for coronary artery disease in an urban Indian population. BMJ Open 2014;4:e005346.  Back to cited text no. 25
    
26.
Rao GH. Aspirin resistance: A fact or a myth? Exp Clin Cardiol 2005;10:17-20.  Back to cited text no. 26
    
27.
Rao GH. Need for a specific rapid point-of-care assay. World Heart J 2006;1:63-78.  Back to cited text no. 27
    
28.
Rao GH, Michiels JJ. Aspirin resistance: Does it exist? Semin Thromb Hemost 2007;33:210-4.  Back to cited text no. 28
    
29.
Rao GH, Fareed J. Aspirin prophylaxis for the prevention of thrombosis: Expectations and limitations. Thrombosis 2012;2012:104707.  Back to cited text no. 29
    
30.
Rao GH. Aspirin resistance: Clinical Significance. J Clin Prev Cardiovasc 2012;1:118-29.  Back to cited text no. 30
    
31.
Michelson AD. Flow cytometry: A clinical test for platelet function. J Am Soc Hematol 1996;87:4025-36.  Back to cited text no. 31
    
32.
Reinke M, Piller M, Brune K. Development of an enzyme-linked immunosorbent assay of thromboxane B2 using a monoclonal antibody. Prostaglandins 1989;37:577-86.  Back to cited text no. 32
    
33.
Montine TJ, Sonnen JA, Milne G, Baker LD, Breitner JC. Elevated ratio of urinary metabolites of thromboxane and prostacyclin is associated with adverse cardiovascular events in ADAPT. PLoS One 2010;5:e9340.  Back to cited text no. 33
    
34.
Olson MT, Kickler TS, Lawson JA, McLean RC, Jani J, FitzGerald GA, et al. Effect of assay specificity on the association of urine 11-dehydro thromboxane B2 determination with cardiovascular risk. J Thromb Haemost 2012;10:2462-9.  Back to cited text no. 34
    
35.
Schwarz UR, Geiger J, Walter U, Eigenthaler M. Flow cytometry analysis of intracellular VASP phosphorylation for the assessment of activating and inhibitory signal transduction pathways in human platelets – Definition and detection of ticlopidine/clopidogrel effects. Thromb Haemost 1999;82:1145-52.  Back to cited text no. 35
    
36.
Aleil B, Ravanat C, Cazenave JP, Rochoux G, Heitz A, Gachet C. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases. J Thromb Haemost 2005;3:85-92.  Back to cited text no. 36
    
37.
Aradi D, Magyarlaki T, Tokés-Füzesi M, Rideg O, Vorobcsuk A, Komócsi A. Comparison of conventional aggregometry with VASP for monitoring P2Y12-specific platelet inhibition. Platelets 2010;21:563-70.  Back to cited text no. 37
    
38.
Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle, et al. Cytochrome P450 2C19 loss-of-function. Blood 2006;108:2244-7.  Back to cited text no. 38
    
39.
Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: Response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003;107:2908-13.  Back to cited text no. 39
    
40.
Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: A review of the evidence. J Am Coll Cardiol 2005;45:1157-64.  Back to cited text no. 40
    
41.
Mullangi R, Srinivas NR. Clopidogrel: Review of bio analytical methods, pharmacokinetics/pharmacodynamics, and update on recent trends in drug-drug interaction studies. Biomed Chromatogr 2009;23:26-41.  Back to cited text no. 41
    
42.
Park KJ, Chung HS, Kim SR, Kim HJ, Han JY, Lee SY. Clinical, pharmacokinetic, and pharmacogenetic determinants of clopidogrel resistance in Korean patients with acute coronary syndrome. Korean J Lab Med 2011;31:91-4.  Back to cited text no. 42
    
43.
Perry CG, Shuldiner AR. Pharmacogenomics of anti-platelet therapy: How much evidence is enough for clinical implementation? J Hum Genet 2013;58:339-45.  Back to cited text no. 43
    
44.
Gladding P, White H, Voss J, Ormiston J, Stewart J, Ruygrok P, et al. Pharmacogenetic testing for clopidogrel using the rapid INFINITI analyzer: A dose-escalation study. JACC Cardiovasc Interv 2009;2:1095-101.  Back to cited text no. 44
    
45.
Gladding P, Panattoni L, Webster M, Cho L, Ellis S. Clopidogrel pharmacogenomics: Next steps: A clinical algorithm, gene-gene interactions, and an elusive outcomes trial. JACC Cardiovasc Interv 2010;3:995-1000.  Back to cited text no. 45
    
46.
Rao GH, Kakkar VJ. Coronary Artery Disease in South Asians: Epidemiology, Risk Factors, Prevention. New Delhi, India: Jaypee Medical Publishers; 2001.  Back to cited text no. 46
    
47.
Rao GH, Thanikachalam S. Coronary Artery Disease: Risk Factors Pathophysiology and Prevention. New Delhi, India: Jaypee Medical Publishers; 2005.  Back to cited text no. 47
    
48.
Mohan V, Rao GH. Diabetes Mellitus: Epidemiology, Risk Management and Prevention. New Delhi, India; Jaypee Medical Publishers; 2007.  Back to cited text no. 48
    
49.
Rao GH. Handbook of Coronary Artery Disease. New Delhi, India: Macmillan Medical Communications; 2016.  Back to cited text no. 49
    
50.
Rao GH, Reddy M. Handbook of Biotechnology, Bioengineering, and Biomedical Applications. Bangalore, India: National Design Research Foundation, Institution of Engineers; 2016.  Back to cited text no. 50
    
51.
Rao GH, Gandhi PG. Need for a non-invasive diagnostic platform for early detection and management of cardiometabolic disorders. J Clin Prev Cardiol 2014;3:93-8.  Back to cited text no. 51
    
52.
Gandhi PG, Rao GH. The spectral analysis of photoplethysmography to evaluate an independent cardiovascular risk factor. Int J Gen Med 2014;7:539-47.  Back to cited text no. 52
    
53.
Gandhi PG, Rao GH. Detection of neuropathy using a sudomotor test in type 2 diabetes. Degener Neurol Neuromuscul Dis 2015;5:1-7.  Back to cited text no. 53
    
54.
Rao GH, Gandhi PG, Sharma V. Clinical complications of type-2 diabetes mellitus in South Asians and Chinese populations: An overview. J Diabetes Metabol 2014;5:420. doi: 10.4172/2155-6156.1000420.  Back to cited text no. 54
    
55.
Rao GH. Risk assessment, risk prediction, and effective management of risk factors for cardiovascular diseases. J Clin Prev Cardiol Editor 2012;1:9-10.  Back to cited text no. 55
    
56.
Rao GH. Antiplatelet therapies: An overview. J Clin Prev Cardiol 2016. [In press].  Back to cited text no. 56
    
57.
Rao GH. Prevention of vascular disease and development of affordable healthcare for all: Thinking out of box (view point). J Clin Prev Cardiol 2012;1:31-4.  Back to cited text no. 57
    
58.
Rao GH, Thethi I, Fareed J. Vascular disease: Obesity and excess weight as modulators of risk. Expert Rev Cardiovasc Ther 2011;9:525-34.  Back to cited text no. 58
    
59.
Divani AA, Luft AR, Flaherty JD, Rao GH. Direct diagnosis is superior to risk factor prediction tools for management of vessel wall disease. Front Neurol 2012;3:36.  Back to cited text no. 59
    
60.
Rao GH, Bharathi M. Mother and child nutrition:First major step for prevention of cardio metabolic disorders. J Cardiol Photon 2016;109:179-86.  Back to cited text no. 60
    
61.
Rao GH. Management of type-2 diabetes with anti-platelet therapies: Special reference to aspirin. Front Biosci (Schol Ed) 2011;3:1-15.  Back to cited text no. 61
    
62.
Rao GH. Non-traditional approaches to diagnosis and management of type-2 diabetes mellitus: Point of view. J Diabetes Metab 2014;6:489. doi: 10.4172/2155-6156.1000489.  Back to cited text no. 62
    
63.
Sharma NR, Rao GH. Diabetes management: Expectations and limitations. J Diabet Metab 2014;7:4. doi: 10.4172/2155-6156.1000662.  Back to cited text no. 63
    


    Figures

  [Figure 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Monitoring Vascu...
Aspirin Resistance
Clopidogrel Resi...
Detection of the...
References
Article Figures

 Article Access Statistics
    Viewed2024    
    Printed126    
    Emailed0    
    PDF Downloaded164    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]