Related Articles

Objective

To examine the interaction between cigarette smoking and clinical efficacy of clopidogrel in STEMI.

Background

Cigarette smoking induces CYP1A2, which converts clopidogrel into its active metabolite, and prior studies suggest greater inhibition of platelet aggregation by clopidogrel in smokers of ≥10 cigarettes/day.

Methods

The effect of clopidogrel compared with placebo on angiographic and clinical outcomes was examined in CLARITY-TIMI 28, a randomized trial of 3429 STEMI patients, stratified by smoking intensity as follows: not current smokers (N=1732), smokers of 1-9 (N=206), 10-19 (N=354), 20-29 (N=715), and ≥30 cigarettes/day (N=422). Logistic regression was used to adjust for other baseline characteristics and interaction terms to test for effect modification.

Results

Although clopidogrel reduced the rate of the primary endpoint of a closed infarctrelated artery or death/MI before angiography in CLARITY-TIMI 28, the benefit was especially marked among those who smoked ≥10 cigarettes/day (adjusted OR 0.49, 95% CI 0.37-0.66; P<0.0001) as compared to those who did not (adjusted OR 0.72, 95% CI 0.57-0.91; P=0.006; Pinteraction=0.04). Similarly, clopidogrel was significantly more effective at reducing the rate of cardiovascular death, MI, or urgent revascularization through 30 days among those who smoked ≥10 cigarettes/day (adjusted OR 0.54, 95% CI 0.38-0.76; P=0.0004) compared with those who did not (adjusted OR 0.98; 95% CI 0.75-1.28; P=0.87; Pinteraction=0.006).

Conclusions

Cigarette smoking appears to positively modify the beneficial effect of clopidogrel on angiographic and clinical outcomes. This study demonstrates that common clinical factors that influence the metabolism of clopidogrel may impact its clinical effectiveness.

Objectives

We sought to determine smoking-related hazard ratios (HRs) and population-attributable risk percentage (PAR%) for serious clinical events and death among HIV-positive persons, whose smoking prevalence is higher than in the general population.

Methods

For 5472 HIV-infected persons enrolled from 33 countries in the Strategies for Management of Antiretroviral Therapy clinical trial, we evaluated the relationship between baseline smoking status and development of AIDS-related or serious non-AIDS events and overall mortality.

Results

Among all participants, 40.5% were current smokers and 24.8% were former smokers. Adjusted HRs were higher for current than for never smokers for overall mortality (2.4; P<.001), major cardiovascular disease (2.0; P=.002), non-AIDS cancer (1.8; P=.008), and bacterial pneumonia (2.3; P<.001). Adjusted HRs also were significantly higher for these outcomes among current than among former smokers. The PAR% for current versus former and never smokers combined was 24.3% for overall mortality, 25.3% for major cardiovascular disease, 30.6% for non-AIDS cancer, and 25.4% for bacterial pneumonia.

Conclusions

Smoking contributes to substantial morbidity and mortality in this HIV-infected population. Providers should routinely integrate smoking cessation programs into HIV health care.

Background

Postulating that serotonin (5-HT), released from smoking-activated platelets could be involved in smoking-induced vascular modifications, we studied its catabolism in a series of 115 men distributed as current smokers (S), never smokers (NS) and former smokers (FS) who had stopped smoking for a mean of 13 years.

Methodology/Principal Findings

5-HT, monoamine oxidase (MAO-B) activities and amounts were measured in platelets, and 5-hydroxyindolacetic acid (5-HIAA)—the 5-HT/MAO catabolite—in plasma samples. Both platelet 5-HT and plasma 5-HIAA levels were correlated with the 10-year cardiovascular Framingham relative risk (P<0.01), but these correlations became non-significant after adjustment for smoking status, underlining that the determining risk factor among those taken into account in the Framingham risk calculation was smoking. Surprisingly, the platelet 5-HT content was similar in S and NS but lower in FS with a parallel higher plasma level of 5-HIAA in FS. This was unforeseen since MAO-B activity was inhibited during smoking (P<0.00001). It was, however, consistent with a higher enzyme protein concentration found in S and FS than in NS (P<0.001). It thus appears that MAO inhibition during smoking was compensated by a higher synthesis. To investigate the persistent increase in MAO-B protein concentration, a study of the methylation of its gene promoter was undertaken in a small supplementary cohort of similar subjects. We found that the methylation frequency of the MAOB gene promoter was markedly lower (P<0.0001) for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity.

Conclusions/Significance

This is one of the first reports that smoking induces an epigenetic modification. A better understanding of the epigenome may help to further elucidate the physiopathology and the development of new therapeutic approaches to tobacco addiction. The results could have a larger impact than cardiovascular damage, considering that MAO-dependent 5-HT catabolism is also involved in addiction, predisposition to cancer, behaviour and mental health.

The relationship of smoking to total mortality and to the prevalence of cardiorespiratory symptoms has been studied in three prospective surveys in west central Scotland in which 18 786 people attended a multiphasic screening examination. The prevalence of respiratory symptoms, and to a lesser extent cardiovascular symptoms, increased with the number of cigarettes smoked, with inhalation, and with a younger age of starting to smoke. A lower prevalence of respiratory symptoms in both sexes was observed in smokers of filter cigarettes than in smokers of plain cigarettes, and in those who smoked cigarettes with lower tar levels, irrespective of whether these were filtered or plain. In general, the relationships found between smoking and mortality were similar to those reported by other workers. Current cigarette smokers had a death rate from all causes which was twice that of those who had never smoked. No difference was found between the mortality rates of smokers of plain and filter cigarettes.

Objective

To estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV-infection.

Design

Patients who reported smoking status, and no previous CVD prior to enrolment into D:A:D were included. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Duration since stopping smoking was calculated for persons who had reported current smoking during follow-up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD – MI plus invasive coronary artery procedure or death from other CHD); CVD (CVD – CHD plus carotid artery endarterectomy or stroke); and all-cause mortality.

Methods

Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow-up. Incidence rate ratios (IRR) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral treatment.

Results

27,136 patients had smoking status reported, with a total of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events respectively. The adjusted IRR of CVD in patients who stopped smoking during follow-up decreased from 2.32 within the first year of stopping to 1.49 after 3+ years compared to those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all cause mortality.

Conclusion

The risk of CVD events in HIV-positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV positive patients.

Objective

To evaluate the joint effect of cigarette smoking and alcohol consumption on mortality.

Methods

A population-based cohort of 66,743 Chinese men aged 30–89 in Shanghai, China recruited from 1996 to 2000. Lifestyle data were collected using structured questionnaires. As of November 2004, follow-up for the vital status of 64,515 men was completed and death information was further confirmed through record linkage with the Shanghai Vital Statistics Registry. Associations were evaluated by Cox regression analyses.

Results

2,514 deaths (982 from cancers, 776 from cardiovascular diseases (CVD)) were identified during 297,396 person-years of follow-up. Compared to never-smokers, both former and current smokers had significantly elevated mortality from any cause, CVD, and cancer; risk increased with amount of smoking. Intake of 1–7 drinks/week was associated with reduced risk of death, particularly CVD death (hazard ratio (HR): 0.7, 95% confidence interval (CI): 0.5, 1.0), whereas intake of >42 drinks/week was related to increased mortality, particularly cancer-related death (HR: 1.7, 95% CI: 1.1, 2.5). The HR for total mortality associated with moderate alcohol consumption increased from 0.8 (95% CI: 0.6, 1.0) for non-smokers to 1.0 (0.9, 1.2) for moderate smokers and 1.4 (95% CI: 1.2, 1.7) for heavy smokers. Heavy drinkers and heavy smokers had the highest mortality (HR: 1.9, 95% CI: 1.6, 2.4).

Conclusions

Light and moderate alcohol consumption reduced mortality from CVD. This beneficial effect, however, was offset by cigarette smoking.

Background

Smoking remains the most common preventable cause of death. Very little tobacco exposure can increase cardiovascular disease risk. The relationship between smoking, sex, and weight remains unclear.

Methods

Between September 1992 and June 2007, 2582 consenting patients starting the Ottawa Hospital Weight Management program were grouped by sex and smoking status. “Former smokers” (771 females, 312 males) had quit for at least 1 year. “Smokers” (135 females, 54 males) smoked > 9 cigarettes daily. There were 979 females and 331 males who never smoked. Using SAS 9.2 statistical software, the prevalence of coronary artery disease (CAD), type 2 diabetes (T2DM), major depressive disorder (MDD), and medication use among the groups was compared (Chi-square [χ2]). Anthropometric measurements, lipid, glucose and thyroid levels were compared using analysis of variance (ANOVA). Interactions were assessed using 2-way ANOVA analysis for continuous data, and logistic regression for discrete data.

Results

Smokers were more likely to have MDD (χ2), lower high-density lipoprotein levels and higher triglyceride levels than other groups. Former smokers had a greater prevalence of CAD, T2DM on pharmacotherapy, and impaired fasting glucose than other groups. They were also more likely to be taking lipid-lowering agents and antihypertensives (χ2). Never smokers had less MDD, CAD, and were less likely to be on antidepressants than the other groups. Males were more likely to have CAD and T2DM than females. Females were more likely to have MDD than males. Interactions between smoking status and sex were found for age, weight, fasting glucose and thyroid-stimulating hormone levels.

Conclusion

Obese never smokers suffer from the fewest chronic diseases. Obese former smokers have a greater prevalence of CAD, T2DM on pharmacotherapy, and impaired fasting glucose than other groups. Thus, clinicians and researchers should avoid combining former smokers with never smokers as “nonsmokers” in research and treatment decisions. The results of this study call for a longitudinal study comparing these groups over the weight management program.

Objective To investigate the impact of smoking on overall mortality and life expectancy in a large Japanese population, including some who smoked throughout adult life.

Design The Life Span Study, a population-based prospective study, initiated in 1950.

Setting Hiroshima and Nagasaki, Japan.

Participants Smoking status for 27 311 men and 40 662 women was obtained during 1963-92. Mortality from one year after first ascertainment of smoking status until 1 January 2008 has been analysed.

Main outcome measures Mortality from all causes in current, former, and never smokers.

Results Smokers born in later decades tended to smoke more cigarettes per day than those born earlier, and to have started smoking at a younger age. Among those born during 1920-45 (median 1933) and who started smoking before age 20 years, men smoked on average 23 cigarettes/day, while women smoked 17 cigarettes/day, and, for those who continued smoking, overall mortality was more than doubled in both sexes (rate ratios versus never smokers: men 2.21 (95% confidence interval 1.97 to 2.48), women 2.61 (1.98 to 3.44)) and life expectancy was reduced by almost a decade (8 years for men, 10 years for women). Those who stopped smoking before age 35 avoided almost all of the excess risk among continuing smokers, while those who stopped smoking before age 45 avoided most of it.

Conclusions The lower smoking related hazards reported previously in Japan may have been due to earlier birth cohorts starting to smoke when older and smoking fewer cigarettes per day. In Japan, as elsewhere, those who start smoking in early adult life and continue smoking lose on average about a decade of life. Much of the risk can, however, be avoided by giving up smoking before age 35, and preferably well before age 35.

Toward the establishment of evidence-based recommendations for the prevention of prostate cancer recurrence after treatment, we examined the association between smoking and prostate cancer recurrence in a retrospective cohort study of 1416 men who underwent radical prostatectomy. Surgeries were performed by a single surgeon at Johns Hopkins Hospital between January 1, 1993, and March 31, 2006. Smoking status at 5 years before and 1 year after surgery was assessed by survey. Prostate cancer recurrence was defined as confirmed re-elevation of prostate-specific antigen levels, local recurrence, metastasis, or prostate cancer death. The cumulative incidence of recurrence was 34.3% among current smokers, 14.8% among former smokers, and 12.1% among never smokers, with a mean follow-up time of 7.3 years. Men who were current smokers at 1 year after surgery were more likely than never smokers to have disease recurrence after adjusting for pathological characteristics, including stage and grade (hazard ratio for recurrence = 2.31, 95% confidence interval = 1.05 to 5.10). This result suggests an association between cigarette smoking and risk of prostate cancer recurrence.

Clopidogrel is approved for reduction of atherothrombotic events in patients with cardiovascular (CV) and cerebrovascular disease. Dual antiplatelet therapy with aspirin and clopidogrel decreases the risk of major adverse cardiac events after acute coronary syndrome or percutaneous coronary intervention, compared with aspirin alone. Due to concern about gastrointestinal bleeding in patients who are receiving clopidogrel and aspirin therapy, current guidelines recommend combined use of a proton pump inhibitor (PPI) to decrease the risk of bleeding. Data from previous pharmacological studies have shown that PPIs, which are extensively metabolized by the cytochrome system, may decrease the ADP-induced platelet aggregation of clopidogrel. Results from retrospective cohort studies have shown a higher incidence of major CV events in patients receiving both clopidogrel and PPIs than in those without PPIs. However, other retrospective analyses of randomized clinical trials have not shown that the concomitant PPI administration is associated with increased CV events among clopidogrel users. These controversial results suggest that large specific studies are needed. This article reviews the metabolism of clopidogrel and PPIs, existing clinical data regarding the interaction between clopidogrel and PPIs, and tries to provide recommendations for health care professionals.

Introduction

Smoking is among the leading causes of premature mortality and preventable death in the United States. Although smoking contributes to the probability of developing chronic illness, little is known about the relationship between quitting smoking and the presence of chronic illness. The present study investigated the association between diagnoses of one or more chronic diseases (diabetes, hypertension, or high cholesterol) and smoking status (former or current smoker).

Methods

The data analyzed were a subset of questions from a 155-item telephone-administered community survey that assessed smoking status, demographic characteristics, and presence of chronic disease. The study sample consisted of 3,802 randomly selected participants.

Results

Participants with diabetes were more likely to report being former smokers, after adjusting for sociodemographic characteristics, whereas having hypertension or high cholesterol was not associated significantly with smoking status. The likelihood of being a former smoker did not increase as number of diagnosed chronic diseases increased. Participants who were women, older (aged 65+), or single were significantly less likely to be former smokers. Participants with at least a college degree, those with incomes of US$50,000+, and those who were underweight or obese were more likely to be former smokers.

Discussion

These findings were inconsistent with research that has suggested that having a chronic illness or experiencing a serious medical event increases the odds of smoking cessation. Supporting prior research, we found that being male, having a higher income, and being obese were associated with greater likelihood of being a former smoker.

In patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS), both periprocedural acute myocardial infarction and bleeding complications have been shown to be associated with early and late mortality. Current standard antithrombotic therapy after coronary stent implantation consists of lifelong aspirin and clopidogrel for a variable period depending in part on the stent type. Despite its well-established efficacy in reducing cardiac-related death, myocardial infarction, and stroke, dual antiplatelet therapy with aspirin and clopidogrel is not without shortcomings. While clopidogrel may be of little beneficial effect if administered immediately prior to PCI and may even increase major bleeding risk if coronary artery bypass grafting is anticipated, early discontinuation of the drug may result in insufficient antiplatelet coverage with thrombotic complications. Optimal and rapid inhibition of platelet activity to suppress ischemic and thrombotic events while minimizing bleeding complications is an important therapeutic goal in the management of patients undergoing percutaneous coronary intervention. In this article we present an overview of the literature on clinical trials evaluating the different aspects of antithrombotic therapy in patients undergoing PCI and discuss the emerging role of these agents in the contemporary era of early invasive coronary intervention. Clinical trial acronyms and their full names are provided in Table 1.

Background

Although the harms of smoking are well established, it is unclear how they extend into old age in the Chinese.

Aim

To examine the relationship of smoking with all‐cause and major cause‐specific mortality in elderly Chinese men and women, respectively, in Hong Kong.

Methods

Mortality by smoking status was examined in a prospective cohort study of 56 167 (18 749 men, 37 416 women) Chinese aged ⩾65 years enrolled from 1998 to 2000 at all the 18 elderly health centres of the Hong Kong Government Department of Health.

Results

After a mean follow‐up of 4.1 years, 1848 male and 2035 female deaths occured among 54 214 subjects (96.5% successful follow‐up). At baseline, more men than women were current smokers (20.3% vs 4.0%) and former smokers (40.8% vs 7.9%). The adjusted RRs (95% CI) for all‐cause mortality in former and current smokers, compared with never smokers, were 1.39 (1.23 to 1.56) and 1.75 (1.53 to 2.00) in men and 1.43 (1.25 to 1.64) and 1.38 (1.14 to 1.68) in women, respectively. For current smokers, the RRs (95% CI) for all‐cause mortality were 1.59 (1.39 to 1.82), 1.72 (1.48 to 2.00) and 1.84 (1.43 to 2.35) for daily consumption of 1–9, 10–20 and >21 cigarettes, respectively (p for trend <0.001). RRs (95% CI) were 1.49 (1.30 to 1.72) and 2.20 (1.88 to 2.57) in former and current smokers for all deaths from cancer, and 1.24 (1.04 to 1.47) and 1.57 (1.28 to 1.94) for all cardiovascular deaths, respectively. Quitters had significantly lower risks of death than current smokers from all causes, lung cancer, all cancers, stroke and all cardiovascular diseases.

Conclusions

In old age, smoking continues to be a major cause of death, and quitting is beneficial. Smoking cessation is urgently needed in rapidly ageing populations in the East.

Clopidogrel (Plavix ®), an antiplatelet drug chemically similar to ticlopidine, is marketed for secondary prevention of thrombotic complications in patients with a history of myocardial infarction (MI), ischemic stroke, or peripheral arterial disease.

Marketing authorization was based mainly on the CAPRIE trial, a study that involved 19 185 patients. In this trial of secondary cardiovascular prevention, clopidogrel was slightly more effective than acetylsalicylic acid (ASA) (325 mg/d) according to statistical analysis of a combined end point (ischemic stroke or MI or death of vascular causes). The difference was more marked in the subgroup of patients with obstructive arterial disease of the lower limbs.

Clopidogrel was well tolerated in this trial. The only adverse effects more frequent with clopidogrel than with ASA were rash and diarrhea.

Clopidogrel showed no hematologic toxicity, an adverse effect that restricts use of ticlopidine.

Lack of long-term follow up in real clinical settings prevents meaningful estimation of the safety profile or of risk of drug interactions.

Objective To assess the risk of lung cancer in smokers of medium tar filter cigarettes compared with smokers of low tar and very low tar filter cigarettes.

Design Analysis of the association between the tar rating of the brand of cigarette smoked in 1982 and mortality from lung cancer over the next six years. Multivariate proportional hazards analyses used to assess hazard ratios, with adjustment for age at enrolment, race, educational level, marital status, blue collar employment, occupational exposure to asbestos, intake of vegetables, citrus fruits, and vitamins, and, in analyses of current and former smokers, for age when they started to smoke and number of cigarettes smoked per day.

Setting Cancer prevention study II (CPS-II).

Participants 364 239 men and 576 535 women, aged ≥ 30 years, who had either never smoked, were former smokers, or were currently smoking a specific brand of cigarette when they were enrolled in the cancer prevention study.

Main outcome measure Death from primary cancer of the lung among participants who had never smoked, former smokers, smokers of very low tar (≤ 7 mg tar/cigarette) filter, low tar (8-14 mg) filter, high tar (≥ 22 mg) non-filter brands and medium tar conventional filter brands (15-21 mg).

Results Irrespective of the tar level of their current brand, all current smokers had a far greater risk of lung cancer than people who had stopped smoking or had never smoked. Compared with smokers of medium tar (15-21 mg) filter cigarettes, risk was higher among men and women who smoked high tar (≥ 22 mg) non-filter brands (hazard ratio 1.44, 95% confidence interval 1.20 to 1.73, and 1.64, 1.26 to 2.15, respectively). There was no difference in risk among men who smoked brands rated as very low tar (1.17, 0.95 to 1.45) or low tar (1.02, 0.90 to 1.16) compared with those who smoked medium tar brands. The same was seen for women (0.98, 0.80 to 1.21, and 0.95, 0.82 to 1.11, respectively).

Conclusion The increase in lung cancer risk is similar in people who smoke medium tar cigarettes (15-21 mg), low tar cigarettes (8-14 mg), or very low tar cigarettes (≤ 7 mg). Men and women who smoke non-filtered cigarettes with tar ratings ≥ 22 mg have an even higher risk of lung cancer.

The objective of this study was to assess disparities in health care utilization, by smoking status, among adults in the United States. We used 1999–2004 National Health and Nutrition Examination Survey (NHANES) data from 15,332 adults. Multivariate logistic regressions were used to examine the relationship between smoking status (current, former, and never smoker), with health care utilization. After controlling for demographic characteristics, current smokers and former smokers who quit either <2 years or ≥10 years prior to the survey were more likely to have had inpatient admission in the past year than never smokers. Current smokers did not differ from never smokers on whether they had an outpatient visit in the past year. They were, however, more likely than never smokers to have ≥4 outpatient visits. Smokers who quit either <2 years ago or ≥10 years ago were more likely to have had an outpatient visit than never smokers. Former smokers were more likely than never smokers to have ≥4 outpatient visits regardless of when they quit. Our results show that cigarette smoking is associated with higher health care utilization for current and former smokers than for never smokers. Frequent hospitalization and outpatient visits translate into higher medical costs. Therefore, more efforts are needed to promote interventions that discourage smoking initiation and encourage cessation.

Objective

To characterize further the relationship between smoking history and Parkinson disease (PD) risk by considering temporal and qualitative features of smoking exposure, including duration, average intensity, and recentness, as well as the relative importance of smoking during different periods of life.

Methods

We prospectively assessed incident PD from 1992 to 2001 among 79,977 women and 63,348 men participating in the Cancer Prevention Study II Nutrition Cohort, according to their cigarette smoking status and lifetime smoking histories.

Results

During follow-up, 413 participants had definite or probable PD confirmed by their treating neurologists or medical record review. Compared with never smokers, former smokers had a relative risk (RR) of 0.78 (95% CI 0.64 to 0.95) and current smokers had an RR of 0.27 (95% CI 0.13 to 0.56). On average, participants with more years smoked, more cigarettes per day, older age at quitting smoking, and fewer years since quitting smoking had lower PD risk. The relative risks and trends did not vary significantly by sex. The cumulative incidence of PD was lowest among participants who quit smoking at later ages. A 30% to 60% decreased risk of PD was apparent for smoking as early as 15 to 24 years before symptom onset, but not for smoking 25 or more years before onset.

Conclusions

The lower risk of Parkinson disease among current and former smokers varied with smoking duration, intensity, and recentness. The dependence of this association on the timing of smoking during life is consistent with a biologic effect.

Objective To evaluate the association of environmental exposure to tobacco smoke from husbands and from work, as well as from family members in early life, with all cause mortality and mortality due to cancer or cardiovascular disease in Chinese women.

Design Ongoing prospective cohort study in Shanghai, China.

Participants Of 72 829 women who had never smoked, 65 180 women provided information on smoking by their husbands, and 66 520 women provided information on exposure to tobacco smoke at work and in early life from family members.

Main outcome measures All cause mortality and cause specific mortality with the main focus on cancer and cardiovascular disease. Cumulative mortality according to exposure status, and hazard ratios.

Results Exposure to tobacco smoke from husbands (mainly current exposure) was significantly associated with increased all cause mortality (hazard ratio 1.15, 95% confidence interval 1.01 to 1.31) and with increased mortality due to cardiovascular disease (1.37, 1.06 to 1.78). Exposure to tobacco smoke at work was associated with increased mortality due to cancer (1.19, 0.94 to 1.50), especially lung cancer (1.79, 1.09 to 2.93). Exposure in early life was associated with increased mortality due to cardiovascular disease (1.26, 0.94 to 1.69).

Conclusions In Chinese women, exposure to environmental tobacco smoke is related to moderately increased risk of all cause mortality and mortality due to lung cancer and cardiovascular disease.

Context

Smoking causes death in many ways, but the rate of risk reduction after quitting, compared to continuing to smoke, is uncertain. There is inadequate or insufficient evidence to infer the presence or absence of a causal relationship between smoking and ovarian cancer and colorectal cancer.

Objective

To assess the relation between cigarette smoking and smoking cessation on total and cause-specific mortality in women.

Design, Setting, and Participants

Prospective observational study of 104,519 female participants in the Nurses’ Health Study followed from 1980 to 2004.

Main Outcome Measure

Hazard ratios for total mortality, further categorized into vascular and respiratory diseases, cancers and other causes.

Results

A total of 12483 deaths occurred in this cohort, 4485 (35.9%) among never smokers, 3602 (28.9%) among current smokers, and 4396 (35.2%) among past smokers. Compared to never smokers, current smokers had an increased risk of total mortality (hazard ratio = 2.81, 95% confidence interval (CI) = 2.68–2.95) and all major cause-specific mortality evaluated. The hazard ratio for cancers classified by the 2004 Surgeon General’s report to be smoking-related was 7.25 (CI:6.43–8.18) and for other cancers, 1.58 (CI:1.45–1.73). The hazard ratio for colorectal cancer was 1.63 (CI:1.29–2.05) for current smokers and 1.23 (CI:1.02–1.49) for former smokers, compared to never smokers. A significant association was not observed for ovarian cancer. Significant trends were observed for earlier age at initiation for total mortality (P=0.003), respiratory disease mortality (P=0.001), and all smoking-caused cancer mortality (P=0.001). The excess risk for all-cause mortality decreases to the level of a never smoker 20 years after quitting, with different timeframes for risk reduction observed across outcomes. Approximately 64% of deaths among current smokers and 28% of deaths among former smokers were attributable to cigarette smoking.

Conclusions

Most of the excess risk of vascular mortality due to smoking can be eliminated rapidly upon cessation and within 20 years for lung diseases. Postponing the age of smoking initiation has a dramatic impact on risk of respiratory disease, lung cancer, and other smoking-caused cancer deaths and little effect on other cause-specific mortality. These data suggest that smoking increases the risk of colorectal cancer mortality but not ovarian cancer mortality.

Antiplatelet drug resistance is one of the urgent issues in current cardiovascular medicine. Many platelet function tests have been used to define responsiveness of patients with cardiovascular disease to aspirin and clopidogrel. In most studies, cut-off values of platelet function tests for defining responsiveness to antiplatelets were chosen arbitrarily. Different tests provided wide-ranging figures of the prevalence of aspirin and clopidogrel resistance, suggesting poor correlation between currently available platelet function tests. Measurement of platelet size seems to be a promising approach for monitoring antiplatelet drug therapy. This commentary highlights some limitations of studies on aspirin and clopidogrel resistance in patients undergoing coronary interventions.

Obesity and smoking represent the leading preventable causes of morbidity and mortality in the United States. This study compared the prevalence of obesity among smokers seeking cessation treatment (n = 1428) versus a general population (n = 4081) of never smokers, former smoker, and current smokers. Data from treatment-seeking smokers in the Wisconsin Smokers’ Health Study (WSHS) and individuals who completed the National Health and Nutrition Examination Survey (NHANES) 2005-06 were pooled and obesity rates and other health characteristics were compared. The prevalence of obesity was significantly higher among WSHS treatment-seeking smokers (36.8%) versus NHANES current smokers (29.6%), but the obesity rates of WSHS treatment-seeking smokers did not differ from NHANES former smokers (36.5%) or never smokers (36.5%). Treatment-seeking smokers were more likely to be female and to have higher educational attainment compared to NHANES participants. Analysis of health characteristics revealed treatment-seeking smokers had higher levels of dietary fiber and vitamin C and lower blood levels of total cholesterol, triglycerides, and fasting glucose compared to NHANES current smokers. Results suggest that treatment-seeking smokers may have a different health profile than current smokers in the general population. Health care providers should be aware of underlying heath issues, particularly obesity, in patients seeking smoking cessation treatment.

Smoking is a major risk factor of morbidity and mortality. It is well established that monoamine oxidase (MAO) activity is decreased in smokers. Serotonin (5-HT), a major substrate for MAO that circulates as a reserve pool stored in platelets, is a marker of platelet activation. We recently reported that smoking durably modifies the platelet 5-HT/MAO system by inducing a demethylation of the MAO gene promoter resulting in high MAO protein concentration persisting more than ten years after quitting smoking. The present data enlarges the results to another MAO substrate, norepinephrine (NE), further confirming the central role of MAO in tobacco use-induced diseases. Thus, MAO could be a readily accessible and helpful marker in the risk evaluation of smoking-related diseases, from cardiovascular and pulmonary diseases to depression, anxiety and cancer. The present review implements the new finding of epigenetic regulation of MAO and suggests that smoking-induced MAO demethylation can be considered as a hallmark of smoking-related cancers similarly to other aberrant DNA methylations.

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin has been successful in reducing ischemic events in a wide range of patients with cardiovascular diseases. However, the anti-ischemic effects of DAPT may also be associated with gastrointestinal (GI) complications including ulceration and bleeding particularly in ‘high risk’ and elderly patients. Current guidelines recommend the use of proton-pump inhibitors (PPIs) to reduce the risk of GI bleeding in patients treated with DAPT. However, pharmacodynamic studies suggest an effect of PPIs on clopidogrel metabolism with a resultant reduction in platelet inhibitory effects. Similarly, several observational studies have demonstrated reduced clopidogrel benefit in patients who coadministered PPIs. Although recent US Food and Drug Administration and European Medicines Agency statements discourage PPI (particularly omeprazole) and clopidogrel coadministration, the 2009 AHA/ACC/SCAI PCI guidelines do not support a change in current practice in the absence of adequately powered prospective randomized clinical trial data. The data regarding pharmacologic and clinical interactions between PPI and clopidogrel therapies are herein examined and treatment strategies are provided.

Background

Patients with reduced responsiveness to clopidogrel often have diminished platelet inhibition, a factor associated with increased rates of major adverse cardiovascular events. Clinical trials that have focused on reducing high on-treatment platelet reactivity (HPR) with an additional loading dose of clopidogrel have reported varying effects. Prasugrel, a newer thienopyridine, exhibits a more consistent antiplatelet effect and more rapid onset time when compared to clopidogrel. We hypothesize that prasugrel reloading would be more effective than clopidogrel reloading in patients with HPR after an initial loading dose of clopidogrel.

Method/Design

Comparison of Prasugrel and Clopidogrel Reloading on High Platelet Reactivity in Clopidogrel-loaded Patients Undergoing Percutaneous Coronary Intervention (PRAISE-HPR) is a prospective, randomized, open-label, active controlled study. A total of 76 patients undergoing percutaneous coronary intervention (PCI), with HPR after administration of a loading dose of clopidogrel will be randomly assigned to either prasugrel or clopidogrel groups, and patients in each group will be reloaded with 20 mg of prasugrel or 300 mg of clopidogrel. The primary endpoint will be HPR at 24 hours after PCI, as determined by the VerifyNow assay during the study period. The rate of sustained high platelet reactivity and 30-day clinical outcomes will also be measured.

Discussion

PRAISE-HPR is a randomized controlled clinical trial to investigate the efficacy and safety of reloading prasugrel and clopidogrel in suppressing residual high platelet reactivity. The results will be made publicly available in the year 2013.

Trial registration

NCT01609647

Background

Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive.

The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events.

Methods

Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded.

Discussion

This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management.

This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).