Showing papers by "Paolo Raggi published in 2018"

Association Between Baseline LDL-C Level and Total and Cardiovascular Mortality After LDL-C Lowering: A Systematic Review and Meta-analysis.

Abstract: Importance Effects on specific fatal and nonfatal end points appear to vary for low-density lipoprotein cholesterol (LDL-C)–lowering drug trials. Objective To evaluate whether baseline LDL-C level is associated with total and cardiovascular mortality risk reductions. Data Sourcesand Study Selection Electronic databases (Cochrane, MEDLINE, EMBASE, TCTMD, ClinicalTrials.gov, major congress proceedings) were searched through February 2, 2018, to identify randomized clinical trials of statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies. Data Extraction and Synthesis Two investigators abstracted data and appraised risks of bias. Intervention groups were categorized as “more intensive” (more potent pharmacologic intervention) or “less intensive” (less potent, placebo, or control group). Main Outcomes and Measures The coprimary end points were total mortality and cardiovascular mortality. Random-effects meta-regression and meta-analyses evaluated associations between baseline LDL-C level and reductions in mortality end points and secondary end points including major adverse cardiac events (MACE). Results In 34 trials, 136 299 patients received more intensive and 133 989 received less intensive LDL-C lowering. All-cause mortality was lower for more vs less intensive therapy (7.08% vs 7.70%; rate ratio [RR], 0.92 [95% CI, 0.88 to 0.96]), but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with greater reductions in all-cause mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.91 [95% CI, 0.86 to 0.96];P = .001; absolute risk difference [ARD], −1.05 incident cases per 1000 person-years [95% CI, −1.59 to −0.51]), but only when baseline LDL-C levels were 100 mg/dL or greater (P Conclusions and Relevance In these meta-analyses and meta-regressions, more intensive compared with less intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels. This association was not present when baseline LDL-C level was less than 100 mg/dL, suggesting that the greatest benefit from LDL-C–lowering therapy may occur for patients with higher baseline LDL-C levels.

Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction Sex Differences and Mechanisms

Abstract: Background:Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infa...

Brain Correlates of Mental Stress-Induced Myocardial Ischemia.

Abstract: OBJECTIVE Coronary artery disease (CAD) is a major cause of morbidity and mortality, and despite important advances in our understanding of this disorder, the underlying mechanisms remain under investigation. Recently, increased attention has been placed on the role of behavioral factors such as emotional stress on CAD risk. Brain areas involved in memory and the stress response, including medial prefrontal cortex, insula, and parietal cortex, also have outputs to the peripheral cardiovascular system. The purpose of this study was to assess the effects of mental stress on brain and cardiac function in patients with CAD. METHODS CAD patients (N = 170) underwent cardiac imaging with [Tc-99m] sestamibi single-photon emission tomography at rest and during a public speaking mental stress task. On another day, they underwent imaging of the brain with [O-15] water positron emission tomography (PET) during mental stress (arithmetic and public speaking) and control conditions. RESULTS Patients with mental stress-induced myocardial ischemia showed increased activation with stress in anterior cingulate, inferior frontal gyrus, and parietal cortex (p < .005). This was seen with both arithmetic stress and public speaking stress. Arithmetic stress was additionally associated with left insula activation, and public speaking with right pre/postcentral gyrus and middle temporal gyrus activation (p < .005). CONCLUSIONS These findings suggest that mental stress-induced myocardial ischemia is associated with activation in brain areas involved in the stress response and autonomic regulation of the cardiovascular system. Altered brain reactivity to stress could possibly represent a mechanism through which stress leads to increased risk of CAD-related morbidity and mortality.

Inflammatory response to mental stress and mental stress induced myocardial ischemia.

Abstract: Background Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. Methods Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. Results Of 607 patients analyzed in this study, (mean age 63 ± 9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p Conclusion Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI.

Coronary and Peripheral Vasomotor Responses to Mental Stress.

Abstract: Background Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvascular endothelial function and will be reflected in the peripheral microvascular circulation. Methods and Results In 38 patients aged 59±8 years undergoing coronary angiography, endothelium‐dependent and endothelium‐independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS induced by mental arithmetic testing. Peripheral microvascular tone during MS was measured using peripheral arterial tonometry (Itamar Inc, Caesarea, Israel) as the ratio of digital pulse wave amplitude compared to rest (peripheral arterial tonometry ratio). MS increased the rate‐pressure product by 22% (±23%) and constricted epicardial coronary arteries by −5.9% (−10.5%, −2.6%) (median [interquartile range]), P =0.001, without changing CBF. Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P =0.001, without epicardial coronary diameter change (0.1% [−10.9%, 8.2%], P =not significant). The MS‐induced CBF response correlated with endothelium‐dependent CBF changes with acetylcholine ( r =0.38, P =0.03) but not with the response to nitroprusside. The peripheral arterial tonometry ratio also correlated with the demand‐adjusted change in CBF during MS ( r =−0.60, P =0.004), indicating similarity between the microcirculatory responses to MS in the coronary and peripheral microcirculation. Conclusions The coronary microvascular response to MS is determined by endothelium‐dependent, but not endothelium‐independent, coronary microvascular function. Moreover, the coronary microvascular responses to MS are reflected in the peripheral microvascular circulation.

Young Women With Coronary Artery Disease Exhibit Higher Concentrations of Interleukin-6 at Baseline and in Response to Mental Stress

Abstract: Background Young women with coronary artery disease (CAD), a group with high psychosocial burden, were previously shown to have higher levels of interleukin‐6 (IL‐6) compared with men of similar ag...

Use of High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia: A Cohort Study.

Abstract: Background Many patients with coronary artery disease (CAD) are routinely referred for surveillance stress testing despite recommendations against it. Objective To determine whether low levels of resting high-sensitivity cardiac troponin I (hs-cTnI) can identify persons without inducible myocardial ischemia. Design Observational study. Setting A university-affiliated hospital network. Patients Persons with stable CAD: 589 in the derivation group and 118 in the validation cohort. Measurements Presence of inducible myocardial ischemia was determined by myocardial perfusion imaging with technetium-99m single-photon emission computed tomography during either treadmill or pharmacologic stress testing. Resting plasma hs-cTnI was measured within 1 week of the stress test, and the negative predictive value (NPV) for inducible ischemia was calculated. The derivation cohort was followed for 3 years for incident cardiovascular death and myocardial infarction. Results In the derivation cohort, 10 of 101 patients with an hs-cTnI level below 2.5 pg/mL had inducible myocardial ischemia (NPV, 90% [95% CI, 83% to 95%]) and 3 of 101 had inducible ischemia involving at least 10% of the myocardium (NPV, 97% [CI, 92% to 99%]). In the validation cohort, 4 of 32 patients with an hs-cTnI level below 2.5 pg/mL had inducible ischemia (NPV, 88% [CI, 71% to 96%]) and 2 of 32 had ischemia of 10% or greater (NPV, 94% [CI, 79% to 99%]). After a median follow-up of 3 years in the derivation cohort, no adverse events occurred in patients with an hs-cTnI level below 2.5 pg/mL, compared with 33 (7%) cardiovascular deaths or incident myocardial infarctions among those with an hs-cTnI level of 2.5 pg/mL or greater. Limitation The data may not be applicable to a population without known CAD or to persons with unstable angina, and the modest sample sizes warrant further validation in a larger cohort. Conclusion Very low hs-cTnI levels may be useful in excluding inducible myocardial ischemia in patients with stable CAD. Primary funding source National Institutes of Health.

Myocardial Ischemia and Mobilization of Circulating Progenitor Cells.

Abstract: Background The response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and Results A total of 356 patients with stable coronary artery disease underwent 99mTc‐sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD34 + and CD34 + /chemokine (C‐X‐C motif) receptor 4 PCs were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal‐derived factor‐1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34 + /chemokine (C‐X‐C motif) receptor 4 (−18%, P =0.01) after stress that was inversely correlated with the magnitude of ischemia ( r =−0.19, P =0.003). In contrast, patients without ExMI had an increase in CD34 + /chemokine (C‐X‐C motif) receptor 4 (14.7%, P =0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P P =0.03), suggesting a greater decrease in PCs in those with a greater change in stromal‐derived factor‐1α level with exercise. Conclusions ExMI is associated with a significant decrease in circulating levels of CD34 + /chemokine (C‐X‐C motif) receptor 4 PCs, likely attributable, at least in part, to stromal‐derived factor‐1α–mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.

Effects of vitamin D supplementation on carotid intima-media thickness in HIV-infected youth.

Abstract: Allison Ross Eckard, Paolo Raggi, Mary Ann O’Riordan, Julia C. Rosebush, Danielle Labbato, Ann Chahroudi, Joshua H. Ruff, Christopher T. Longenecker, Vin Tangpricha, and Grace A. McComsey Medical University of South Carolina, Charleston, SC, USA; Emory University School of Medicine, Atlanta, GA, USA; Mazankowski Alberta Heart Institute and University of Alberta, Edmonton, Alberta, Canada; Case Western Reserve University and Rainbow Babies & Children’s Hospital, Cleveland, OH, USA

Prices For Common Cardiovascular Drugs In The US Are Not Consistently Aligned With Value

Abstract: Health care reimbursement agencies in countries other than the US often rely on cost-effectiveness evidence for drug coverage decisions, signaling to drug manufacturers their expectations for value...

Response by Vaccarino et al to Letter Regarding Article, “Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction: Sex Differences and Mechanisms”

Abstract: Circulation. 2018;138:548–549. DOI: 10.1161/CIRCULATIONAHA.118.035546 548 Viola Vaccarino, MD, PhD J. Douglas Bremner, MD Paolo Raggi, MD In Response: We thank Drs Singh and Mian for their interest in our recently published paper.1 We are aware that reproductive hormone status could be an important correlate of vascular response to stress in women. However, menopausal status had little influence on such responses in our study. As mentioned in a footnote to Table 5 in our published paper, adding menopausal status to the model for women did not materially change the results. In our data, although the prevalence of ever smoking was slightly lower in female controls compared with male controls (25% versus 30%), it was slightly higher among women who had survived a myocardial infarction (MI) than among their male counterparts (61% versus 56%). Drs Singh and Mian are correct in pointing out that the prevalence of ever smoking in our post-MI female sample was quite high, and much higher than in the general population of women. However, this is not surprising given that our study is based on a young post-MI sample, and smoking is a stronger risk factor for MI at younger age2 and a stronger risk factor among women than men.3 We chose to use ever smoking as our main smoking exposure variable in consideration of the fact that patients may change their smoking habits after an acute MI. In addition, in our sample there was no difference in current smoking status between post-MI women (23%) and post-MI men (24%), and current smoking among controls was quite rare in both sexes (5% in women and 4% in men). Although we agree with Drs Singh and Mian that depression has been previously associated with endothelial dysfunction and mental stress–induced myocardial ischemia, depression was not associated with vascular function changes with mental stress in our sample of post-MI patients, and, as shown in Table 5 of our published paper, neither psychosocial factors (including depression) nor use of antidepressants meaningfully explained the sex difference in myocardial ischemia with mental stress. We did not perform myocardial perfusion imaging among controls because this test would not be informative in a low-risk, asymptomatic population. We respectfully disagree with Drs Singh and Mian that such testing could be of value in patients with risk factors but without a history of coronary artery disease, if they are asymptomatic and have no indications for this test, as shown, for example, in patients with diabetes mellitus.4 Furthermore, it would expose such individuals to unnecessary radiation.