A Brief Journey into the History of the Arterial Pulse

Objective. This paper illustrates the evolution of our knowledge of the arterial pulse from ancient times to the present. Several techniques for arterial pulse evaluation throughout history are discussed. Methods. Using databases including Worldcat, Pubmed, and Emory University Libraries' Catalogue, the significance of the arterial pulse is discussed in three historical eras of medicine: ancient, medieval, and modern. Summary. Techniques used over time to analyze arterial pulse and its characteristics have advanced from simple evaluation by touch to complex methodologies such as ultrasonography and plethysmography. Today's understanding of the various characteristics of the arterial pulse relies on our ancestors' observations and experiments. The pursuit of science continues to lead to major advancements in our knowledge of the arterial pulse and its application in diagnosis of atherosclerotic disease

Action Mechanisms of Antirheumatic Herbal Medicines

Rheumatoid arthritis (RA) is a chronic inflammatory and debilitating joint disorder that causes severe impairment and reduces the quality of life. The available synthetic medicines used as standard therapy for RA have numerous side effects that can compromise their therapeutic outcomes. Thus, the demand for alternative and complementary medicines is increasing. A search of English articles in PubMed, Scopus, Google Scholar, and Web of Science databases was carried out on probable mechanisms of action of herbs with the antirheumatic property. Herbal medicines stated in folk medicine face acceptance concerns by the medical community because of the lack of scientific documents regarding their physio-pharmacological mechanisms. This chapter aims to review the possible antirheumatic effects of various herbs, including Rosmarinus officinalis L., Curcuma longa, and Crocus sativus, their related mechanisms, and preclinical applications, in order to recall the therapeutic properties of herbal medicine. However, more clinical trials are required to confirm the safety and efficacy of these antirheumatic herbal medicines

Oxidative Stress is Associated with Increased Pulmonary Artery Systolic Pressure in Humans

Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine; glutathione, and its oxidized disulphide (GSSG) were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/GSSG couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (p\u3c0.001), gender (p=0.002), mitral regurgitation (p\u3c0.001), left ventricular ejection fraction (p\u3c0.001), left atrial size (p\u3c 0.001), diabetes (p=0.03), Plasma Ln cystine (β=9.53, p\u3c0.001), Ln glutathione (β =-5.4, p=0.002), and Eh glutathione (β =0.21, p=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (β=6.56, p=0.007), mitral regurgitation (β= 4.52, P\u3c0.001), statin use (β =-3.39, p=0.03), left ventricular ejection fraction (β=-0.26, p=0.003), and age (β=0.17, p=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study

Bioactive Lipids and Circulating Progenitor Cells in Patients with Cardiovascular Disease

Bone marrow-derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P) were quantified using mass spectrometry. CPCs were assessed using flow cytometry. S1P levels correlated with the numbers of CD34+, CD34+/CD133+, and CD34+/CXCR4+ CPCs even after adjustment for potential confounding factors. However, no significant correlation was observed between C1P levels and CPC count. Plasma levels of S1P correlated with the number of CPCs in patients with coronary artery disease, suggesting an important mechanistic role for S1P in stem cell mobilization. The therapeutic effects of adjunctive S1P therapy to mobilize endogenous stem cells need to be investigated

Response to letter regarding article by Patel et al: A Novel Biomarker of Oxidative Stress is Associated with Risk of Death in Patients with Coronary Artery Disease

We thank Drs Giral and colleagues for their interest in our work.1 They raise the important query of whether our findings would still persist after adjustment for γ-glutamyltransferase (GGT), given that GGT activity hydrolyzes glutathione (GSH) to produce glutamate+cysteinylglycine. This point, however, is not relevant to our description of GSH/cystine as a useful biomarker of cardiovascular disease, because our samples were all collected with a preservation solution containing a GGT

A Novel Biomarker of Oxidative Stress is Associated with Risk of Death in Patients with Coronary Artery Disease

Background—Free radical scavengers have failed to improve patient outcomes promoting the concept that clinically important oxidative stress (OS) may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of non-free radical mediated oxidative stress with clinical outcomes. Methods and Results—Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7±2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (p\u3c0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (\u3e+1 SD & \u3c-1 SD respectively) were associated with higher mortality (adjusted HR 1.63 (95% CI 1.19-2.21; HR 2.19 (95% CI 1.50-3.19), respectively) compared to those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR 1.92 (95% CI 1.39-2.64) and was independent of and additive to hs-CRP level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. Conclusions—A high burden of OS, quantified by the plasma aminothiols, cystine, glutathione and their ratio is associated with mortality in patients with CAD, a finding that is independent of and additive to the inflammatory burden. Importantly, this data supports the emerging role of non-free radical biology in driving clinically important oxidative stress

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Introduction Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. Methods and Results We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox\u27s proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P\u3c0.0001) and its severity (P\u3c0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden\u27s index) predicted future risk of MI (hazard ratio [HR]=3.2; P\u3c0.0001), cardiac death (HR=2.62; P\u3c0.0001), and the combined endpoint of death and MI (HR=1.9; P\u3c0.0001), even after adjustment of covariates. The C-statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. Conclusion Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD

Circulating CD34+ Progenitor Cells and Risk of Mortality in a Population with Coronary Artery Disease

RATIONALE: Low circulating progenitor cell (PC) numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. OBJECTIVES: To investigate whether low numbers of PCs associate with a greater risk of mortality in a population at high cardiovascular risk. METHODS & RESULTS: Patients undergoing coronary angiography were recruited into two cohorts (1, n=502 and 2, n=403) over separate time periods. PCs were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets co-expressing CD133, VEGFR2 and CXCR4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary endpoint of all-cause death. There was an inverse association between CD34+ and CD34+/CD133+ cell counts and risk of death in Cohort 1 (β=−0.92, p=0.043 and β=−1.64, p=0.019, respectively) that was confirmed in Cohort 2 (β=−1.25, p=0.020 and β=−1.81, p=0.015, respectively). Covariate adjusted HRs in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34+/CD133+ cell counts improved risk prediction metrics beyond standard risk factors. CONCLUSION: Reduced circulating PC counts, identified primarily as CD34+ mononuclear cells or its subset expressing CD133 are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction and cell selection for cell based therapies

Primary Prevention of Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of death worldwide. This article focuses on current guidelines for the primary prevention of CVD and addresses management of key risk factors. Dietary modification, weight loss, exercise, and tobacco use cessation are specific areas where focused efforts can successfully reduce CVD risk on both an individual and a societal level. Specific areas requiring management include dyslipidemia, hypertension, physical activity, diabetes, aspirin use, and alcohol intake. These preventive efforts have major public health implications. As the global population continues to grow, health care expenditures will also rise, with the potential to eventually overwhelm the health care system. Therefore it is imperative to apply our collective efforts on CVD prevention to improve the cardiovascular health of individuals, communities, and nations