Dan Lundblad

Relationship of cigarette smoking and snuff dipping to plasma fibrinogen, fibrinolytic variables and serum insulin. The Northern Sweden MONICA study

The influence of cigarette smoking and use of smokeless tobacco on plasma fibrinogen level, fibrinolytic variables, glucose tolerance and serum insulin was studied in a randomly selected population sample consisting of 604 men and 662 females between 25 and 64 years. Subjects were grouped according to tobacco habits as follows: regular smokers (> 1 cig/day), ex-smokers, snuff dippers, and non-tobacco users. An oral glucose tolerance test was performed on 54% of the participants. Tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) activity were used to study fibrinolysis. Men who smoked had 0.34 g/l (95% CI 0.17 to 0.49) higher fibrinogen level than non-tobacco users and numbers of cigarettes smoked correlated with plasma fibrinogen levels (r = 0.21, P = 0.006). Female smokers had significantly higher fibrinogen levels than ex-smokers but the difference compared with non-smokers was not significant. Snuff dipping did not affect fibrinogen levels. We found no relationship between tPA activity, PAI-1 activity and tobacco use. Post-load plasma glucose was lower in women who smoked, otherwise no influence of tobacco use on glucose levels was seen. Lower post-load insulin levels (-8.8 mU/ml, 95% CI -2.4 to -16.3) than in non-smokers were also found in women who smoked. This was only partially explained by a lower body mass index in smokers. We conclude that cigarette smoking is associated with increased fibrinogen levels, unaltered fibrinolysis, normal glucose tolerance and insulin levels. The use of smokeless tobacco, as moist oral snuff, does not appear to affect these potential cardiovascular risk factors.

Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986–2009

Abstract.  Eriksson M, Holmgren L, Janlert U, Jansson J‐H, Lundblad D, Stegmayr B, Söderberg S, Eliasson M (Department of Public Health and Clinical Medicine, Umeå University, Umeå; Research Department, Norrbotten County Council, Luleå; Department of Medicine, Skellefteå Hospital, Skellefteå; Department of Medicine, Sunderby Hospital, Luleå; and National Board of Health and Welfare, Stockholm, Sweden). Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986–2009. J Intern Med 2011; 269: 219–231.

Fibrinogen and fibrinolytic variables in relation to anthropometry, lipids and blood pressure. The Northern Sweden MONICA Study.

Fibrinolysis is dependent upon plasminogen activator (tPA) activity while high fibrinogen levels increase the risk of thromboembolic events. From a cross-sectional population sample of 1558 men and women aged 25 to 64 years, plasma fibrinogen, tPA activity and plasminogen activator inhibitor-1 (PAI) activity were determined using specific assays. Associations with body mass index (BMI), waist-hip ratio (WHR), serum lipids and blood pressure were calculated with uni- and multivariate models where age and smoking were also introduced. In men age, truncal obesity, short height and low HDL cholesterol independently predicted fibrinogen (R2 0.20) while in women obesity per se, total cholesterol, systolic blood pressure, smoking and age were predictors (R2 0.29). tPA activity was negatively associated with BMI and serum triglyceride levels and positively with age in both sexes. In men diastolic blood pressure (R2 0.22) and in women WHR further independently predicted low fibrinolytic activity. HDL was associated with greater fibrinolysis in women (R2 0.15). Relationships with PAI-1 activity were essentially the reverse of tPA but stronger. Prospective interventional studies are needed to answer the question of causality.

Cardiovascular risk factors in young snuff-users and cigarette smokers

Abstract. We studied cardiovascular risk factors in 21 young men who were habitual snuff‐users, and compared them with the same risk factors in 18 non‐tobacco‐users and 19 cigarette smokers of the same age and body mass index. Both snuff‐users and smokers showed increased levels of alcohol and coffee consumption and a decreased level of physical exercise compared to non‐users. Both groups of tobacco‐users showed increased serum insulin levels compared to the control group at similar blood glucose concentrations. In contrast to the smokers, snuff‐users showed no significant elevation of diastolic blood pressure, haemoglobin concentrations, white cell count, serum cholesterol or triglyceride levels. Snuff users had higher plasma fibrinogen levels than non‐users (P = 0.07). The use of snuff by young men appears to have less impact than smoking on cardiovascular risk factors, with the possible exception of elevated serum insulin and plasma fibrinogen levels.

Time Trends in Symptoms and Prehospital Delay Time in Women vs. Men with Myocardial Infarction Over a 15-Year Period. The Northern Sweden MONICA Study

Background: Few studies have examined the time between onset of myocardial infarction (MI) symptoms and arrival at hospital (prehospital delay time) and symptoms in men vs. women. Aims: To describe prehospital delay time and symptoms in men vs. women with MI and to analyse trends over time and according to age. Methods: The Northern Sweden MONICA myocardial infarction registry, 1989–2003, included 5072 men and 1470 women with a confirmed MI. Results: Typical pain was present in 86% of the men and 81% of the women. The proportion with typical symptoms decreased over time for men and increased for women. Typical symptoms were more common among younger persons than older persons. Insufficiently reported symptoms was unchanged in men over time and decreased among women. Up to the age of 65, no gender differences were seen in the prehospital delay. In the oldest age group (65–74 years) time to hospital was longer than among the younger groups, especially among women. Conclusion: There were no major gender differences in prehospital delay or type of symptoms. However, over time the proportion with typical symptoms decreased in men and increased in women. Older patients had longer prehospital delay and less typical symptoms.

Gender differences in trends of acute myocardial infarction events : the Northern Sweden MONICA study 1985 - 2004.

BackgroundThe registration of non-fatal and fatal MI events initiated 1985 in the WHO MONICA project has been ongoing in northern Sweden since the end of the WHO project in 1995. The purpose of the present study was to analyze gender differences in first and recurrent events, case fatality and mortality in myocardial infarction (MI) in Northern Sweden during the 20-year period 1985 – 2004.MethodsDiagnosed MI events in subjects aged 25–64 years in the Counties of Norrbotten and Västerbotten were validated according to the MONICA protocol. The total number of events registered up to January 1, 2005 was 11,763: 9,387 in men and 2,376 in women.ResultsThe proportion of male/female events has decreased from 5.5:1 to 3:1. For males the reductions were 30% and 70% for first and recurrent MI, respectively, and for women 0% and 40% in the 55–64 year group. For both sexes a 50% reduction in 28-day case fatality was seen in the 25–64 year-group. Mortality was reduced by 69% and 45% in men and women, respectively.ConclusionFirst and recurrent events of myocardial infarction was markedly reduced in men over the 20-year observation period, but for women the reduction was seen only for recurrent infarctions. Case fatality, on the other hand, was markedly reduced for both sexes. As a result of the positive effects on incidence and case fatality a substantial reduction was seen in total mortality, most pronounced for men.

Hyperinsulinemia predicts low tissue plasminogen activator activity in a healthy population: The Northern Sweden MONICA study☆

Fibrinogen levels predict atherothrombotic disease, and impaired fibrinolysis has been proposed as a risk factor for myocardial infarction. Fibrinolysis is mainly dependent on the activity of tissue plasminogen activator (tPA) and its inhibitor plasminogen activator inhibitor type-1 (PAI-1). Oral glucose tolerance tests were performed in 318 randomly selected healthy men and 324 women aged 25 to 64 years. tPA activity was strongly predicted by fasting insulin in both univariate analysis (r = -.37 and -.34 in men and women, respectively) and multivariate analysis with age, anthropometric measurements, lipids, and blood pressure included. Fasting insulin was the strongest predictor of PAI-1 activity (r = .49 and .51). In women, the influence of fasting insulin level on tPA and PAI-1 activity was consistently stronger after than before menopause, and a threshold effect was seen with distinctly lower fibrinolytic activity in the highest quartile of insulin (> 7.0 mU/L). In men, the relation between insulin and fibrinolytic variables was linear. Fibrinogen levels were not related to insulin or glucose levels after adjustment for age and other risk factors in a multiple regression. Subjects with previously unknown diabetes or impaired glucose tolerance tended to have elevated fibrinogen and PAI-1 activity and decreased tPA activity. Our data support previous findings of a strong correlation between insulin and PAI-1 activity in small highly selected groups, and extend them to randomly selected population samples. The strong inverse relation between endogenous insulin levels and tPA activity has not previously been demonstrated in a healthy population.

Better long-term survival in young and middle-aged women than in men after a first myocardial infarction between 1985 and 2006. an analysis of 8630 patients in the Northern Sweden MONICA Study

BackgroundThere is conflicting and only scant evidence on the effect of gender on long-term survival after a myocardial infarction (MI). Our aim was to analyse sex-specific survival of patients for up to 23 years after a first MI in northern Sweden and to describe time trends.MethodsThe Northern Sweden MONICA Myocardial Infarction Registry was linked to The Swedish National Cause of Death Registry for a total of 8630 patients, 25 to 64 years of age, 6762 men and 1868 women, with a first MI during 1985-2006. Also deaths before admission to hospital were included. Follow-up ended on August 30, 2008.ResultsMedian follow-up was 7.1 years, maximum 23 years and the study included 70 072 patient-years. During the follow-up 45.3% of the men and 43.7% of the women had died. Median survival for men was 187 months (95% confidence interval (CI) 179-194) and for women 200 months (95% CI 186-214). The hazard ratio (HR) for all cause mortality after adjustment for age group was 1.092 (1.010-1.18, P = 0.025) males compared to females, i.e. 9 percent higher survival in women. After excluding subjects who died before reaching hospital HR declined to 1.017 (95%CI 0.93-1.11, P = 0.7). For any duration of follow-up a higher proportion of women were alive, irrespective of age group. The 5-year survivals were 75.3% and 77.5%, in younger (<57 years) men and women and were 65.5% and 66.3% in older (57-64 years) men and women, respectively. For each of four successive cohorts survival improved. Survival time was longer for women than for men in all age groups.ConclusionsAge-adjusted survival was higher among women than men after a first MI and has improved markedly and equally in both men and women over a 23-year period. This difference was due to lower risk for women to die before reaching hospital.

Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1

Abstract.  Mörner S, Lindqvist P, Mellberg C, Olofsson B‐O, Backman C, Henein M, Lundblad D, Forsberg H (Umeå University Hospital, Umeå; Umeå University, Umeå; Sunderby Hospital, Luleå; Sweden). Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1. J Intern Med 2010; 268:59–65.

Ventricular dysfunction in type 1 myotonic dystrophy: electrical, mechanical, or both?

BACKGROUND Myotonic dystrophy type 1 (DM1) is a systemic disease which affects the heart and may be a cause of sudden death. Conduction disturbances are the major cardiac abnormalities seen in this condition. We sought to assess electrical and mechanical cardiac functions to identify abnormalities that might explain sudden cardiac death in DM1. METHODS Thirty six patients with DM1 and 16 controls were studied using echocardiography including myocardial Doppler. ECG recordings were also obtained. RESULTS Left ventricular (LV) dimensions were maintained but systolic function was reduced (p<0.001), including stroke volume (p<0.05). LV segmental myocardial isovolumic contraction time was prolonged (p<0.001) and correlated with PR interval (p<0.001). Isovolumic relaxation time was prolonged (p<0.05) and filling time was reduced (p<0.001). LV cavity was significantly asynchronous demonstrated by prolonged total isovolumic time (t-IVT) (p<0.001), high Tei index (p<0.001) and low ejection index (p<0.001). Right ventricular (RV) strain was reduced (p<0.001) as were its systolic and diastolic velocities (p<0.05 for both). 22/36 patients had prolonged LV t-IVT>12.3 s/min (upper 95% normal CI), 13 of whom had PR≥200 ms, 11 had QRS duration>120 ms (5 had combined abnormality) and the remaining 5 had neither. Over the 3 years follow up 10 patients had events, 6 of them cardiac. t-IVT was prolonged in 5/6 patients, PR interval in 4 and QRS duration in one. CONCLUSIONS In DM1 patients, LV conventional measurements are modestly impaired but cardiac time relations suggest marked asynchronous cavity function. Although our findings were primarily explained on the basis of long PR interval or broad QRS duration a minority presented an evidence for myocardial cause of asynchrony rather than electrical. Early identification of such abnormalities may guide towards a need for additional electrical resynchronization therapy which may improve survival in a way similar to what has been shown in heart failure trials.