The natural history of coronary heart disease: prognostic factors after recovery from myocardial infarction in 2789 men. The 5-year findings of the coronary drug project.

Pinzon R.T., Veronica V.

Background: It has long been recognized that inflammation plays a critical role in the pathogenesis of ischemic stroke. However, whether leukocyte count and neutrophil-to-lymphocyte ratio are related to stroke severity and functional outcome is uncertain. Objective: This clinical study aimed to evaluate the association of leukocyte count and neutrophil-to-lymphocyte ratio with stroke severity and functional outcome in acute ischemic stroke patients. Methods: This hospital-based, retrospective observational study included 112 subjects with acute ischemic stroke. All subjects had their demographic, clinical, and laboratory data obtained. The leukocyte count and neutrophil-to-lymphocyte ratio were evaluated by stroke severity on admission and 3-month functional outcome. The severity of stroke at admission was measured using the National Institutes of Health Stroke Scale (NIHSS), whereas the Barthel Index was used to measure 3-month functional outcome (BI). We conducted a regression analysis, adjusting for any confounding variables. Results: Higher leukocyte count was significantly associated with increased risk of stroke severity (odds ratio [OR] 1.391, 95% confidence intervals [CI], 1.121-1.725, p: 0.003) and unfavorable functional outcome (OR 1.434, 95% CI, 1.068-1.925, p: 0.017). Higher neutrophil-to-lymphocyte ratio was not significantly associated with increased risk of stroke severity (OR 1.181, 95% CI, 0.947-1.474, p: 0.140) and unfavorable functional outcome (OR 1.246, 95% CI, 0.905-1.716, p: 0.177). Conclusion: Our study indicates that leukocyte count is an independent predictor of stroke severity on admission and unfavorable functional outcome.

Meinert C.L.

Publication is the sine qua non of trials. In the societal sense, there is no lasting information generated from trials, absent publication. Investigators are not finished until they have published their results and have done so regardless of the nature or direction of the results. One might think that paper writing starts when the trial ends and is finished when the results are published but the reality is that it should start early in the course of the trial and continue long after the trial is finished. This chapter is about the paper writing process.

Meinert C.L.

Publication is the sine qua non of trials. In the societal sense, there is no lasting information generated from trials, absent publication. Investigators are not finished until they have published their results and have done so regardless of the nature or direction of the results. One might think that paper writing starts when the trial ends and is finished when the results are published but the reality is that it should start early in the course of the trial and continue long after the trial is finished. This chapter is about the paper writing process.

Pan Y., Zhang J., Wu T., Hou X., Yang Y., Ma X., Ma Y., Zheng Y., XIE X.

Previous studies suggested that baseline white blood cell count and apolipoprotein A1 levels were associated with clinical outcomes in patients with coronary heart disease (CAD) who underwent percutaneous coronary intervention (PCI). However, the ratio of baseline white blood cell count-to-apolipoprotein A1 level (WAR) and CAD after PCI have not been investigated. The present study investigated the effects of baseline WAR on long-term outcomes after PCI in patients with CAD. A total of 6050 patients with CAD who underwent PCI were included in the study. Of these, 372 patients were excluded because no baseline white blood cell counts or apolipoprotein A1 (ApoA1) data was available or because of malignancies or other diseases. Finally, 5678 patients were enrolled in the present study and were divided into 3 groups according to WAR value: lower group - WAR< 5.25 (n = 1889); median group - 5.25 ≤ WAR≤7.15 (n = 1892); and higher group - WAR≥7.15 (n = 1897). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM), after PCI. The average follow-up time was 35.9 ± 22.6 months. A total of 293 patients developed ACM, including 85 (4.5%) patients in the lower group, 90 (4.8%) patients in the median group, and 118 (6.2%) patients in the higher group. The risk of ACM, cardiac mortality (CM), major adverse cardiovascular and cerebrovascular events (MACCEs), and major adverse cardiovascular events (MACEs) increased 62.6% (hazard risk [HR] =1.626, 95%CI: 1.214–2.179, P = 0.001), 45.5% (HR = 1.455, 95%CI: 1.051–2.014, P = 0.024), 21.2% (HR = 1.212, 95%CI: 1.011–1.454, P = 0.038), and 23.8% (HR = 1.238, 95%CI: 1.025–1.495, P = 0.027), respectively, as determined by multivariate Cox regression analyses comparing the patients in the higher group to patients in the lower group. Patients with a WAR≥4.635 had 92.3, 81.3, 58.1 and 58.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, compared to the patients with WAR< 4.635. Every 1 unit increase in WAR was associated with 3.4, 3.2, 2.0 and 2.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, at the 10-year follow-up. The present study indicated that baseline WAR is a novel and an independent predictor of adverse long-term outcomes in CAD patients who underwent PCI.

Avci B.Ş., Avci A., Dönmez Y., Kaya A., Gülen M., Özer A.İ., Bulut A., Koç M., Nazik H., Satar S.

Background. Myocardial infarction is the most common cause of death all over the world. There are many studies in predicting mortality. The aim of this study was to determine the effectiveness of hematologic parameters measured at the moment of admission to the emergency room in predicting in-hospital mortality and to determine cutoff values of strongly predictive values. Methods. A total of 681 patients over 18 years of age, whose date could be obtained, were included in the study. From the hemogram parameters, white blood cells (WBC), red cell distribution width (RDW), mean platelet volume (MPV), and neutrophils-to-lymphocytes ratio (NLR) values were determined and recorded. CK-MB and high-sensitive troponin T values were recorded as cardiac markers. For statistical analysis, “SPSS for Windows version 21” package program was used. Results. 62.6% (n = 426) of the patients were male, and 37.4% (n = 255) of the patients were female. The NLR was found to be the strongest predictor (area under the curve (AUC), 0.783, SD = 0.052, 95% confidence interval (CI)). It was found that the WBC value came in the second place after NLR as a strong predictor of mortality (AUC, 0.702, SD = 0.075, 95% CI). Conclusion. According to the hemogram results which were acquired with a simple and cheap method, we found that WBC and especially NLR values obtained with a simple method can be used as powerful predictors.

Zhou W., Wang T., Zhu L., Wen M., Hu L., Huang X., You C., Li J., Wu Y., Wu Q., Bao H., Cheng X.

Pokharel Y., Tang Y., Bhardwaj B., Patel K.K., Qintar M., O'Keefe J.H., Kulkarni K.R., Jones P.H., Martin S.S., Virani S.S., Spertus J.A.

Studies of incident coronary heart disease risk within low-density lipoprotein (LDL) subclass (small, dense vs large, buoyant) have shown mixed results. No prospective cohort study has examined the association of small, dense, or large, buoyant LDL with mortality after myocardial infarction (MI).The objective of the study was to examine association of LDL pattern after MI and death.In 2476 patients hospitalized for MI, LDL pattern (A [large, buoyant], A/B [mixed], and B [small, dense]) was established by ultracentrifugation using Vertical Auto Profile. Using time-to-event analysis, we examined the association with 5-year mortality within LDL patterns, after adjusting for important patient and treatment characteristics. We additionally adjusted for LDL cholesterol (LDL-C) and triglyceride levels and used directly measured LDL-C and non-high-density lipoprotein cholesterol as exposures.Patterns A, A/B, and B were present in 39%, 28%, and 33% of patients, respectively, with incident rates (per 1000 patient-years) of 50, 34, and 24 for all-cause and 24, 19, and 10 for CV mortality. The hazard ratios (95% confidence interval) with LDL patterns A/B and B compared with pattern A were 0.77 (0.61, 0.99) and 0.67 (0.51, 0.88) for all-cause, 0.94 (0.67, 1.33) and 0.69 (0.46, 1.03) for cardiovascular, and 0.64 (0.45, 0.91) and 0.65 (0.45, 0.93) for noncardiovascular mortalities, respectively. Results were similar when further adjusted for LDL-C and triglycerides, or with LDL-C and non-high-density lipoprotein cholesterol as exposures.Compared with LDL pattern A, pattern B was significantly associated with reduced all-cause and non-CV mortalities with a trend for lower CV mortality after MI, independent of LDL-C and triglycerides.

ISHIMARU T., ARPHORN S., JIRAPONGSUWAN A.

In Thailand, taxi drivers employed in the informal sector often experience hazardous working conditions. Previous studies revealed that elevated Hematocrit (HCT) is a predictor of cardiovascular disease (CVD) risk. This study assessed factors associated with HCT in taxi drivers to predict their occupational CVD risk factors. A cross-sectional study was conducted on 298 male taxi drivers who joined a health check-up campaign in Bangkok, Thailand. HCT and body mass index were retrieved from participant health check-up files. Self-administered questionnaires assessed demographics, driving mileage, working hours, and lifestyle. Statistical associations were analyzed using stepwise linear regression. Our results showed that obesity (p=0.007), daily alcohol drinking (p=0.003), and current or past smoking (p=0.016) were associated with higher HCT levels. While working hours were not directly associated with HCT levels in the current study, the effect on overworking is statistically arguable because most participants worked substantially longer hours. Our findings suggest that taxi drivers' CVD risk may be increased by their unhealthy work styles. Initiatives to improve general working conditions for taxi drivers should take into account health promotion and CVD prevention. The policy of providing periodic health check-ups is important to make workers in the informal sector aware of their health status.

Stein E.A., Raal F.

In both epidemiologic and genetic studies, increased levels of Lp(a) have been associated with increased risk for cardiovascular diseases as well as aortic stenosis. However, until recently, it has been difficult to lower levels of Lp(a). Diet and lifestyle have little effect on plasma levels of Lp(a) which are mainly genetically determined. Emerging therapeutic agents which have recently become available, or which are undergoing clinical trials, can significantly lower Lp(a) levels. Studies with these agents will hopefully be able to provide more direct information whether reductions in Lp(a) will reduce CVD events independently of reduction in LDL-cholesterol levels.

Schwartz G.G., Do R.Q.

Canner P.L.

AbstractThe Coronary Drug Project, which was conducted during 1966 to 1974, was a randomized, double‐blind, placebo‐controlled trial of five lipid‐modifying agents—estrogens at two dosage levels, dextrothyroxine, clofibrate, and niacin—in 8341 men with previous myocardial infarction. The primary efficacy outcome was all‐cause mortality for the entire follow‐up period. The first three named regimens were terminated early because of adverse effects. Only niacin significantly reduced the risk of (1) cardiovascular events during a mean follow‐up of 6.2 years and (2) all‐cause mortality during 6.2 years with study treatment plus an additional 9 years of post‐trial follow‐up. Analyses of treatment–placebo differences with respect to all‐cause mortality, subdivided by level of adherence to the study prescription and by amount of change in serum cholesterol level, could not be properly interpreted because reasons for good/poor adherence and for cholesterol changes in the placebo group were not well defined.

Canner P.L.

The Coronary Drug Project (CDP) was a randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of five lipid-modifying agents in men with previous myocardial infarction (MI). The patients were followed for a minimum of 5 years to determine whether pharmaceutical modification of blood lipids would lead to improved survival and a reduction in cardiovascular (CV) mortality and morbidity. A secondary objective was to identify baseline prognostic factors for CV mortality and morbidity in the placebo group of patients. This chapter describes the study design and methods used in the CDP. It then presents results of the project. Finally, the chapter presents conclusions and lessons learned form the project.

Told R., Fuchsjäger-Mayrl G., Wolzt M., Popa-Cherecheanu A., Schmetterer L., Garhofer G.

Pentoxifylline, a nonselective phosphodiesterase inhibitor, shows vasodilator effects in certain vascular beds and reduces blood viscosity. We have previously shown that under states of vasoconstriction an interaction between circulating erythrocytes and leukocytes may play a role in the control of blood flow. The reason for this observation is not entirely clear but may be related to a mechanical interaction between red and white blood cells. In the present study we hypothesized that pentoxifylline may alter this interaction during oxygen-induced vasoconstriction. 24 healthy male subjects participated in this double masked, randomized, placebo-controlled 2 way cross over trail. In order to increase white blood cell count (WBC) count, 300 μg of G-CSF was administered intravenously. Vasoconstriction of retinal vessels was induced by oxygen inhalation. 400 mg of pentoxifylline or placebo was infused at two different study days. White blood cell flux was assessed with the blue-field entoptic technique. Vessel calibers were measured with a dynamic vessel analyzer (DVA) and red blood cell velocity (RBCV) was determined with laser Doppler velocimetry (LDV). Retinal blood flow was calculated based on retinal vessel diameters and RBCV. Administration of G-CSF induced a significant increase in WBC, both in the placebo and the pentoxifylline group ( p < 0.01 for both groups). Retinal vessel diameter, RBCV, calculated retinal blood flow and white blood cell flow were not altered by administration of pentoxifylline. Hyperoxia induced a pronounced decrease in retinal blood flow parameters. No difference was observed between groups during oxygen breathing in vessel diameters ( p = 0.54), RBCV ( p = 0.34), calculated retinal blood flow ( p = 0.3) and white blood cell flow ( p = 0.26). Our data indicate that short time administration of pentoxifylline does not alter the oxygen-induced effect on ocular blood flow parameters during leukocytosis. Whether long-term treatment could improve retinal blood flow under states of vasoconstriction remains to be investigated. • PTX does not reverse effects of increased WBC on retinal blood flow regulation • PTX not altering retinal O 2 -reactivity during vasoconstriction and leukocytosis • PTX: blood flow not affected by leukocytosis or leukocytosis and vasoconstriction

Little P.J., Chait A., Januszewski A.S., Bobik A., O’Neal D., Jenkins A.J.

Dyslipidemia is a major risk factor for atherosclerosis in both diabetic and nondiabetic subjects, which is a common cause of morbidity and premature mortality. Based on and supported by favorable outcomes of clinical trials, drugs targeting lipoprotein metabolism are widely used, particularly in developed countries. Drugs to improve lipid levels, in particular to lower low-density lipoprotein (LDL) cholesterol (LDL-C), are commonly used for the primary and secondary prevention of cardiovascular disease. Of the LDL-C-lowering drugs, HMG-CoA reductase inhibitors (“statins”) are particularly effective at reducing cardiovascular disease, both in people with and without diabetes mellitus [1, 2], with more intensive LDL-C lowering being more effective than less intensive LDL-C lowering [3–12]. Statins are effective cardioprotective agents in both type 1 and type 2 diabetes patients [2].

Aje T.O., Miller M.

The Framingham Risk Score has been endorsed by the National Cholesterol Education Program (NCEP) to assess the 10-year risk of coronary heart disease (CHD). Updated evidence-based guidelines may also include lifetime CHD risk and/or the integration of other factors associated with increased risk (i.e., chronic renal insufficiency). The field of preventive cardiology continues to evolve as the prevalence of CHD risk factors in the population change. In this day and age when obesity and type 2 diabetes mellitus have become epidemic, never has the need for identifying areas for CHD prevention been greater. This chapter will highlight results of recently completed clinical trials and the associated advances made toward reducing primary and secondary CHD risk.