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  • Relative familial clustering of cerebral versus coronary ischemic events

    3 July 2018

    Background - Few population-based studies have ascertained both cerebral and coronary events or considered their relative heritability. Differences in heritability of transient ischemic attack and ischemic stroke versus acute coronary syndromes (ACS) may inform risk prediction, genetic studies, and understanding of disease mechanisms. Methods and Results - In a population-based study of all acute vascular events, irrespective of age, we studied family history of myocardial infarction (MI), stroke, and related risk factors in first-degree relatives. To allow for differences in rates of affected first-degree relatives caused by differences in disease incidence, we looked at the extent to which parental history was associated with affected siblings within disease category. Nine hundred six probands (604 men; mean age, 70 years) with ACS and 1015 (484 men; mean age, 73 years) with cerebral events had complete family history data. In ACS probands, parental MI was associated with MI in ≥1 sibling (1 parent with MI: odds ratio, 1.48; 1.04 to 2.10; P=0.03; both parents with MI: odds ratio, 5.97; 3.23 to 11.03; P<0.0001). In probands with cerebral events, however, parental stroke was not associated with sibling stroke. The overall frequency of ≥2 siblings with the same condition was also greater in probands with ACS than in those with cerebral events (odds ratio, 5.43; 3.03 to 9.76; P<0.00001), despite similar overall incidence of MI and stroke in our study population. One hundred forty-two (15.7%) cases of ACS occurred in families with ≥2 affected first-degree relatives compared with 56 (5.1%) transient ischemic attack/strokes. All results were similar when analyses were confined to probands with MI only versus stroke only, and independent of smoking. Conclusions - Heritability of coronary events was greater than that of cerebral events, such that MI was more likely to cluster in families than was stroke. © 2011 American Heart Association, Inc.

  • Impact of completeness of ascertainment of minor stroke on stroke incidence: implications for ideal study methods.

    3 July 2018

    BACKGROUND AND PURPOSE: Reliable comparisons of stroke incidence are important. To determine the impact of systematic assessment of patients referred with transient ischemic attack on the measured incidence and severity of stroke, we compared 2 population-based studies. METHODS: Patients with first-ever stroke ascertained during 2006 through 2010 from the Dijon Stroke Registry and the Oxford Vascular (OXVASC) Study were studied. Both studies comply with the criteria for ideal incidence studies, but the OXVASC Study also systematically assessed all patients referred with transient ischemic attack. Stroke severity was measured by the National Institutes of Health Stroke Scale. RESULTS: Among 902 incident strokes in Dijon and 748 cases in the OXVASC Study, age and gender distribution were comparable, but severity was lower in the OXVASC Study (median National Institutes of Health Stroke Scale, 2 versus 6; P<0.001). Although overall incidence of ischemic stroke was higher in the OXVASC Study (157 versus 98 of 100 000/y; incidence rate ratio, 1.59; 95% confidence interval, 1.24-2.05; P<0.001), this was accounted for by a 3-fold excess incidence of stroke with National Institutes of Health Stroke Scale ≤2 in the OXVASC Study (90 versus 29/100 000/y; P<0.001), with no difference in incidence of more severe ischemic stroke (incidence rate ratio, 0.95; 95% confidence interval, 0.68-1.33). Of all 660 incident ischemic strokes in the OXVASC Study, 375 (56.8%) cases had an National Institutes of Health Stroke Scale ≤2, of which 232 had been ascertained in the transient ischemic attack clinic. Of these 232 minor strokes, only 71 cases had a diagnosis of definite stroke documented in the medical records by the referring physician. CONCLUSIONS: Reliance on routine clinical coding underestimates the incidence of minor stroke. To improve comparability of incidence studies, researchers should assess patients referred with transient ischemic attack, and all studies should stratify incidence rates by stroke severity.

  • Duration of breast feeding and cognitive function: Population based cohort study.

    3 July 2018

    Some evidence suggests that breast feeding is weakly but positively associated with cognitive function. This association has been robust to adjustment for various confounders. The aim of this paper is to determine if duration of breast feeding is associated with cognitive function in late childhood. Data was abstracted from the 1970 British Cohort Study. 11004 liveborn white singletons born during 5-11 April 1970 in the United Kingdom were followed from birth to 10 years. Cognitive function at 10 years is the dependent variable, a latent construct composed of one ability test and three performance measures. Estimates derived from multiple linear regression and structural equation modeling were compared. Effect sizes were estimated using standardized coefficients (SC). Differences in cognitive function according to breast feeding duration were estimated to be small by multiple linear regression (SC = 0.07) and much smaller and non-significant as estimated by structural equation modeling (SC = 0.02) after adjusting for parental socioeconomic status (SES), birth weight, parity, gestational age, maternal age and maternal smoking. Differences in cognitive function according to duration of breast feeding appear to be small and of little clinical importance as estimated by structural equation modeling.

  • Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: Analysis of the time course of risks and benefits in 51 randomised controlled trials

    3 July 2018

    Background Daily aspirin reduces the long-term risk of death due to cancer. However, the short-term effect is less certain, especially in women, effects on cancer incidence are largely unknown, and the time course of risk and benefit in primary prevention is unclear. We studied cancer deaths in all trials of daily aspirin versus control and the time course of effects of low-dose aspirin on cancer incidence and other outcomes in trials in primary prevention. Methods We studied individual patient data from randomised trials of daily aspirin versus no aspirin in prevention of vascular events. Death due to cancer, all non-vascular death, vascular death, and all deaths were assessed in all eligible trials. In trials of low-dose aspirin in primary prevention, we also established the time course of effects on incident cancer, major vascular events, and major extracranial bleeds, with stratifi cation by age, sex, and smoking status. Results Allocation to aspirin reduced cancer deaths (562 vs 664 deaths; odds ratio [OR] 0 85, 95% CI 0 76-0 96, p=0 008; 34 trials, 69 224 participants), par ticularly from 5 years onwards (92 vs 145; OR 0 63, 95% CI 0 49-0 82, p=0 0005), resulting in fewer non-vascular deaths overall (1021 vs 1173; OR 0 88, 95% CI 0 78-0 96, p=0 003; 51 trials, 77 549 participants). In trials in primary prevention, the reduction in non-vascular deaths accounted for 87 (91%) of 96 deaths prevented. In six trials of daily low-dose aspirin in primary prevention (35 535 participants), aspirin reduced cancer incidence from 3 years onwards (324 vs 421 cases; OR 0 76, 95% CI 0 66-0 88, p=0 0003) in women (132 vs 176; OR 0 75, 95% CI 0 59-0 94, p=0 01) and in men (192 vs 245; OR 0 77, 95% CI 0 63-0 93, p=0 008). The reduced risk of major vascular events on aspirin was initially off set by an increased risk of major bleeding, but effects on both outcomes diminished with increasing follow-up, leaving only the reduced risk of cancer (absolute reduction 3 13 [95% CI 1 44-4 82] per 1000 patients per year) from 3 years onwards. Case-fatality from major extracranial bleeds was also lower on aspirin than on control (8/203 vs 15/132; OR 0 32, 95% CI 0 12-0 83, p=0 009).

  • Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials

    3 July 2018

    Background Daily aspirin reduces the long-term incidence of some adenocarcinomas, but effects on mortality due to some cancers appear after only a few years, suggesting that it might also reduce growth or metastasis. We established the frequency of distant metastasis in patients who developed cancer during trials of daily aspirin versus control. Methods Our analysis included all five large randomised trials of daily aspirin (≥75 mg daily) versus control for the prevention of vascular events in the UK. Electronic and paper records were reviewed for all patients with incident cancer. The effect of aspirin on risk of metastases at presentation or on subsequent follow-up (including post-trial follow-up of in-trial cancers) was stratified by tumour histology (adenocarcinoma vs other) and clinical characteristics. Findings Of 17 285 trial participants, 987 had a new solid cancer diagnosed during mean in-trial follow-up of 6?5 years (SD 2?0). Allocation to aspirin reduced risk of cancer with distant metastasis (all cancers, hazard ratio [HR] 0?64, 95% CI 0?48-0?84, p=0?001; adenocarcinoma, HR 0?54, 95% CI 0?38-0?77, p=0?0007; other solid cancers, HR 0?82, 95% CI 0?53-1?28, p=0?39), due mainly to a reduction in proportion of adenocarcinomas that had metastatic versus local disease (odds ratio 0?52, 95% CI 0?35-0?75, p=0?0006). Aspirin reduced risk of adenocarcinoma with metastasis at initial diagnosis (HR 0?69, 95% CI 0?50-0?95, p=0?02) and risk of metastasis on subsequent follow-up in patients without metastasis initially (HR 0?45, 95% CI 0?28-0?72, p=0?0009), particularly in patients with colorectal cancer (HR 0?26, 95% CI 0?11-0?57, p=0?0008) and in patients who remained on trial treatment up to or after diagnosis (HR 0?31, 95% CI 0?15-0?62, p=0?0009). Allocation to aspirin reduced death due to cancer in patients who developed adenocarcinoma, particularly in those without metastasis at diagnosis (HR 0?50, 95% CI 0?34-0?74, p=0?0006). Consequently, aspirin reduced the overall risk of fatal adenocarcinoma in the trial populations (HR 0?65, 95% CI 0?53-0?82, p=0?0002), but not the risk of other fatal cancers (HR 1?06, 95% CI 0?84-1?32, p=0?64; difference, p=0?003). Effects were independent of age and sex, but absolute benefit was greatest in smokers. A low-dose, slow-release formulation of aspirin designed to inhibit platelets but to have little systemic bioavailability was as effective as higher doses.

  • Family history does not predict angiographic localization or severity of coronary artery disease

    3 July 2018

    Background: Family history of MI is an established risk factor for coronary artery disease and subclinical atherosclerosis. Maternal MI and maternal stroke are more common in females than males presenting with acute coronary syndromes (ACS), suggesting sex-specific heritability, but the effects of family history on location and extent of coronary artery disease are unknown. Methods: In a prospective, population-based study (Oxford Vascular Study) of all patients with ACS, family history data for stroke and MI were analysed by sex of proband and affected first degree relatives (FDRs), and coronary angiograms were reviewed, where available. Results: Of 835 probands with one or more ACS, 623 (420 males) had incident events and complete family history data. 351 patients with incident events (56.3%; 266 males) underwent coronary angiography. Neither angiographic disease localization nor severity were associated with sex-of-parent/sex-of-offspring in men or women. Conclusions: Sex-specific family history data do not predict angiographic localization of coronary disease in patients presenting with ACS. Maternal stroke and maternal MI probably affect ACS in females by a mechanism unrelated to atherosclerosis or coronary anatomy. However, family history data may still be useful in risk prediction and prognosis of ACS. © 2012 Elsevier Ireland Ltd.

  • Family history does not predict angiographic localization or severity of coronary artery disease.

    3 July 2018

    BACKGROUND: Family history of MI is an established risk factor for coronary artery disease and subclinical atherosclerosis. Maternal MI and maternal stroke are more common in females than males presenting with acute coronary syndromes (ACS), suggesting sex-specific heritability, but the effects of family history on location and extent of coronary artery disease are unknown. METHODS: In a prospective, population-based study (Oxford Vascular Study) of all patients with ACS, family history data for stroke and MI were analysed by sex of proband and affected first degree relatives (FDRs), and coronary angiograms were reviewed, where available. RESULTS: Of 835 probands with one or more ACS, 623 (420 males) had incident events and complete family history data. 351 patients with incident events (56.3%; 266 males) underwent coronary angiography. Neither angiographic disease localization nor severity were associated with sex-of-parent/sex-of-offspring in men or women. CONCLUSIONS: Sex-specific family history data do not predict angiographic localization of coronary disease in patients presenting with ACS. Maternal stroke and maternal MI probably affect ACS in females by a mechanism unrelated to atherosclerosis or coronary anatomy. However, family history data may still be useful in risk prediction and prognosis of ACS.