Smoking and stroke: A mendelian randomization study

We used the Mendelian randomization design to explore the potential causal association of smoking with ischemic stroke and intracerebral hemorrhage using summary statistics data for 34,217 ischemic stroke cases and 404,630 noncases, and 1,545 cases of intracerebral hemorrhage and 1,481 noncases. Genetic predisposition to smoking initiation (ever smoking regularly), based on up to 372 single‐nucleotide polymorphisms, was statistically significantly positively associated with any ischemic stroke, large artery stroke, and small vessel stroke but not cardioembolic stroke or intracerebral hemorrhage. This study provides genetic support for a causal association of smoking with ischemic stroke, particularly large artery and small vessel stroke. ANN NEUROL 2019;86:468–471     

Smoking and schizophrenia.

Several studies have shown that patients with schizophrenia have an extremely high prevalence of smoking, almost 90%, compared to only 33% in the general population and 45-70% in patients with other psychiatric diagnoses. The reasons for the high prevalence of smoking among schizophrenics is unknown, but it is likely that smoking behavior in schizophrenia may be a complex process, related to numerous interrelationships between the psychopathological, biochemical, and neuropharmacological aspects of smoking and of schizophrenia.     

Smoking and Parkinson's disease.

In a case control study of the relationship between smoking habits and Parkinson's disease a negative association was demonstrated with a relative risk of 0 x 52. A history of smoking up to 20 years earlier was associated with a risk of developing Parkinson's disease equal to about half that in non-smokers. The type of disease, age of onset and rate of progression were associated with a similar reduction in risk implying that in respect of smoking history the disease is homogeneous. The positive correlation of degenerative vascular disease with smoking is further evidence that arteriosclerosis is not involved in the causation of Parkinson's disease. The negative association between Parkinson's disease and smoking is confirmed and is independent of other associated factors. The known and serious risks of smoking far outweigh the possible benefit of lowered risk of Parkinson's disease.     

Statins and stroke.

Inhibitors of HMG-CoA reductase (statins) are potent cholesterol-lowering drugs. Large clinical trials have shown that statins reduce the incidence of cerebrovascular events, which might be surprising because cholesterol is not an established risk factor for stroke. In addition to their cholesterol-lowering properties, statins exert a number of pleiotropic, vasculoprotective actions that include improvement of endothelial function, increased nitric oxide (NO) bioavailability, antioxidant properties, inhibition of inflammatory responses, immunomodulatory actions, regulation of progenitor cells, and stabilization of atherosclerotic plaques. In fact, statins augment cerebral blood flow and confer significant protection in animal models of stroke partly via mechanisms related to the upregulation of endothelial nitric oxide synthase. Retrospective clinical evidence suggests that long-term statin administration may not only reduce stroke risk but also improve outcome. Early secondary prevention trials are underway to test the hypothesis that statin treatment initiated immediately after an event improves short-term outcome. Lastly, recent evidence suggests that sudden discontinuation of statin treatment leads to a rebound effect with downregulation of NO production. Withdrawal of statin treatment may impair vascular function and increase morbidity and mortality in patients with vascular disease.     

Smoking and movement disorders in psychiatric patients.

Previous studies have suggested that tardive dyskinesia may occur more frequently in patients who smoke. Further evidence of an interaction between smoking and movement disorders includes the low lifetime exposure to cigarettes found in Parkinson's disease patients. In this study 126 patients with chronic psychiatric illnesses were blindly evaluated for tardive dyskinesia, neuroleptic-induced parkinsonism, and akathisia. Patients who smoked received significantly higher doses of neuroleptics but did not have significantly more frequent or more severe tardive dyskinesia or parkinsonism. Female smokers did have significantly more akathisia. These results are discussed with regard to interactions between smoking, central dopaminergic tone, and the psychopathology of extrapyramidal syndromes. The effect of smoking on neuroleptic blood levels as well as clinical symptomatology is also discussed.     

Smoking and respiratory irregularity in panic disorder.

BACKGROUND: The biological mechanisms underlying the link between smoking and panic attacks are unknown. Smoking might increase the risk of panic by impairing respiratory system function. METHODS: We evaluated the effect of smoking on respiratory irregularity in patients with panic disorder (PD) and healthy comparison subjects and the role of the respiratory disorders in this effect. We applied the Approximate Entropy index (ApEn), a nonlinear measure of irregularity, to study breath-by-breath baseline respiratory patterns in our sample. RESULTS: Both smoker and nonsmoker patients had more irregular respiratory patterns than healthy subjects. Smoker patients showed higher ApEn indices of baseline respiratory rate and tidal volume than nonsmoker patients (R = 5.4, df = 2,55, p < .01), whereas smoking in healthy subjects did not influence the regularity of respiratory patterns. Respiratory disorders did not account for the influence of smoking on respiratory irregularity. Smokers had more severe panic attacks than nonsmokers. CONCLUSIONS: Smoking may impair vulnerable respiratory function and act as disruptive factor on intrinsic baseline respiratory instability in patients with PD, possibly influencing the onset or maintenance of the disorder.     

Smoking and cognitive function in Parkinson's disease.

The risk of dementia among Parkinson's disease (PD) patients is greatly elevated compared to controls, yet little is known about determinants of cognitive function among PD patients. We assessed the relation between cigarette smoking prior to disease onset and later cognitive function among PD patients (n = 286) and age- and sex-matched controls (n = 1144) participating in the Nurses' Health Study and Health Professionals Follow-up Study. Both groups completed telephone-administered assessments of cognitive function. We used linear regression to calculate mean differences in cognitive test scores across smoking categories, adjusted for age, education, sex, age at onset of PD, and years since diagnosis. PD patients scored significantly worse on all tests than their matched controls. In analyses only among PD cases, but not among controls, current smokers at PD onset scored worse than never smokers on the Telephone Interview for Cognitive Status (difference = -0.82, 95% CI: -1.33, -0.30, P = 0.002) as well as on a global score combining results of all tests (difference = -0.36, 95% CI: -0.72, 0.01, P = 0.06). This difference was equivalent to the difference in global score observed among controls approximately 10 years apart in age. Analyses of pack-years of smoking prior to disease onset gave similar results. These findings, nested in prospective cohort studies, suggest that cigarette smoking prior to disease onset is associated with worse cognitive function in PD.     

Aortic atherosclerosis and stroke.

Methods: Studies using transesophageal echocardiography (TEE) suggest aortic atherosclerosis may be a risk factor for stroke, particularly stroke of undetermined mechanism, but controls in prior studies were not balanced for vascular risk factors. We used TEE to evaluate aortic atherosclerosis in 60 patients with stroke compared with a high-risk control population of 46 subjects. We also examined the possible association of plasma viscosity and fibrinogen levels to aortic atherosclerosis. Results: The mean maximal plaque thickness (MMPT) was similar for the control (2.8 +/- 3.6 mm) and the stroke group (3.3 +/- 3.5 mm), but varied with stroke mechanism. The MMPT was similar in stroke of undetermined and atherosclerotic mechanism [3.5 +/- 4 mm (n = 25) and 4.2 +/- 4.3 mm (n = 16), respectively], significantly greater than in stroke of other mechanisms (1.7 +/- 1.2 mm, P < .05, n = 19). Patients with stroke of undetermined mechanism were four times more likely (95% confidence interval [CI] 1.2-12) to have plaques >/=5 mm compared with controls. Ulcerated plaque was associated with plaque thickness (P < .001) and plasma viscosity (P < .001). Conclusions: Aortic atherosclerosis is associated with stroke of undetermined cause suggesting atherosclerosis is a cause of stroke of undetermined etiology. Plaque ulceration was associated with the thickness of aortic plaque and plasma viscosity.     

Ischemic stroke and depression.

Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 +/- 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 +/- 6.7 years). We required a SIGH-D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH-D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke.     

Quantal bioassay and stroke.

BACKGROUND: Experimental investigation of stroke, in particular the evaluation of therapeutic maneuvers, is difficult because even well-controlled experiments show considerable variability. Optimal use of resources requires efficient statistical analysis. SUMMARY OF REVIEW: A body of experience in pharmacology that is directly applicable to stroke studies is reviewed. The general approach, though well known to pharmacologists, is less familiar to neurologists. This paper attempts to give a survey so that neurologists encountering studies using this general class of analysis will better be able to put the technique into context. The general nature of a quantal bioassay is described, the underlying conceptual models are discussed, and specific examples are given. CONCLUSIONS: The pharmacologist's approach to the analysis of quantal bioassays can easily be adapted to the quantification of results in studies of stroke.     

Cerebral cysticercosis and stroke.

BACKGROUND AND PURPOSE: In 1985 we initiated a protocol for examining the relationship between cerebral cysticercosis and stroke. METHODS: In 420 stroke patients admitted to our department, our standard protocol of tests included blood tests, cardiac investigations, angiography, and immunologic cerebrospinal fluid measures. We assessed the following possible risk factors: arterial hypertension, diabetes, cardiopathy, high levels of cholesterol and triglycerides, smoking, alcohol abuse, and cerebral cysticercosis. RESULTS: Of the 420 patients with stroke, we found cerebral cysticercosis in 31, five of whom were greater than 65 years of age and 26 of whom were less than or equal to 65 years. We determined that cerebral cysticercosis was the only possible risk factor for stroke in one of the five older patients and 15 of the 26 younger and middle-aged patients. Cortical infarctions were found in five of the 31 patients, with cerebral cysticercosis and lacunar infarctions in nine of these patients. One patient had intracystic hemorrhage. In 16 cases, neurological deficit was related to single or multiple cysts, colloids, granulomas, diffuse lesions, or pericystic edema. All patients with cerebral cysticercosis quickly recovered from their neurological deficit, except one who had a hemorrhagic cyst and died and another who remained disabled. CONCLUSIONS: We established that, in patients with neurocysticercosis, occlusion of the small cortical or penetrating vessels at the base of the brain caused by arteriopathy was the most common mechanism of the stroke. Moreover, there is a probable association between cerebral cysticercosis and the susceptibility to stroke, particularly among young and middle-aged patients.     

Coagulopathies and arterial stroke.

Although hypercoagulable states are most often associated with venous thrombosis, arterial thromboses are reported in protein S, protein C, and antithrombin III deficiencies, factor V Leiden and prothrombin gene mutations, hyperhomocysteinemia, dysfibrinogenemia, plasminogen deficiency, sickle cell disease, and antiphospholipid antibody syndrome.