Malte Sund

C-Reactive Protein, a Sensitive Marker of Inflammation, Predicts Future Risk of Coronary Heart Disease in Initially Healthy Middle-Aged Men Results From the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992

BACKGROUND Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events; inflammation elsewhere is also associated with both atherogenesis generally and its thrombotic complications. Recent studies indicate that systemic markers of inflammation can identify subjects at high risk of coronary events. METHODS AND RESULTS We used a sensitive immunoradiometric assay to examine the association of serum C-reactive protein (CRP) with the incidence of first major coronary heart disease (CHD) event in 936 men 45 to 64 years of age. The subjects, who were sampled at random from the general population, participated in the first MONICA Augsburg survey (1984 to 1985) and were followed for 8 years. There was a positive and statistically significant unadjusted relationship, which was linear on the log-hazards scale, between CRP values and the incidence of CHD events (n=53). The hazard rate ratio (HRR) of CHD events associated with a 1-SD increase in log-CRP level was 1.67 (95% CI, 1.29 to 2. 17). After adjustment for age, the HRR was 1.60 (95% CI, 1.23 to 2. 08). Adjusting further for smoking behavior, the only variable selected from a variety of potential confounders by a forward stepping process with a 5% change in the relative risk of CRP as the selection criterion, yielded an HRR of 1.50 (95% CI, 1.14 to 1.97). CONCLUSIONS These results confirm the prognostic relevance of CRP, a sensitive systemic marker of inflammation, to the risk of CHD in a large, randomly selected cohort of initially healthy middle-aged men. They suggest that low-grade inflammation is involved in pathogenesis of atherosclerosis, especially its thrombo-occlusive complications.

Independent association of various smoking characteristics with markers of systemic inflammation in menResults from a representative sample of the general population (MONICA Augsburg Survey 1994/95)

AIMS Aim of the study was to investigate the association between various markers of systemic inflammation and a detailed history of smoking in a large representative sample of the general population. METHODS AND RESULTS The effects of chronic smoking on white blood cell (WBC) count, fibrinogen, albumin, plasma viscosity (PV), and high-sensitivity C-reactive protein (CRP) were measured in 2305 men and 2211 women, age 25-74 years, participating in the third MONICA Augsburg survey 1994/95. In men, current smokers showed statistically significantly higher values for WBC count, fibrinogen, PV, and CRP, compared to never smokers, with intermediate, but only slightly increased values for ex-smokers and for occasional smokers. No consistent associations were seen with albumin. Duration of smoking was positively associated with markers of inflammation as were pack-years of smoking. Conversely, duration of abstinence from smoking was inversely related to these markers. Except for WBC count, no such associations were found in women. CONCLUSION Data from this large representative population show strong associations between smoking and various markers of systemic inflammation in men. They also show that cessation of smoking is associated with a decreased inflammatory response, which may represent one mechanism responsible for the reduced cardiovascular risk in these subjects.

Plasma viscosity and the risk of coronary heart disease : Results from the Monica-Augsburg Cohort Study, 1984 to 1992

Plasma viscosity is determined by various macromolecules, eg, fibrinogen, immunoglobulins, and lipoproteins. It may therefore reflect several aspects involved in cardiovascular diseases, including the effects of classic risk factors, hemostatic disturbances, and inflammation. We examined the association of plasma viscosity with the incidence of a first major coronary heart disease event (CHD; fatal and nonfatal myocardial infarction and cardiac death; n=50) in 933 men aged 45 to 64 years of the MONICA project of Augsburg, Germany. The incidence rate was 7.23 per 1000 person-years (95% confidence interval [CI], 5.37 to 9.53), and the subjects were followed up for 8 years. All suspected cases of an incident CHD event were classified according to the MONICA protocol. There was a positive and statistically significant unadjusted relationship between plasma viscosity and the incidence of CHD. The relative risk of CHD events associated with a 1-SD increase in plasma viscosity (0.070 mPa x s) was 1.60 (95% CI, 1.25 to 2.03). After adjustment for age, total cholesterol, high density lipoprotein cholesterol, smoking, blood pressure, and body mass index, the relative risk was reduced only moderately (1.42; 95% CI, 1.09 to 1.86). The relative risk of CHD events for men in the highest quintile of the plasma viscosity distribution in comparison with the lowest quintile was 3.31 (95% CI, 1.19 to 9.25) after adjustment for the aforementioned variables. A large proportion of events (40%) occurred among men in the highest quintile. These findings suggest that plasma viscosity may have considerable potential to identify subjects at risk for CHD events.

Leisure-Time Physical Activity but Not Work-Related Physical Activity Is Associated With Decreased Plasma Viscosity Results From a Large Population Sample

BACKGROUND Regular leisure-time physical activity (LTPA) is inversely associated with coronary heart disease (CHD). This has been mainly explained by its impact on traditional CHD risk factors, but more recently it was also shown to lower fibrinogen, which largely determines plasma viscosity. No data on the effect of work activity (WA) on plasma viscosity have been published. METHODS AND RESULTS We studied the relationship between self-reported LTPA or WA and plasma viscosity as well as other CHD risk factors in 3522 men and women age 25 to 64 years. Physical activity was assessed by questionnaire. LTPA was inversely associated with plasma viscosity in both sexes. The unadjusted mean differences in plasma viscosity in men between no activity and the highest activity were 0.024 mPa.s (95% confidence interval [CI], 0.016 to 0.032 mPa.s, P < .001) during winter and 0.024 mPa.s (95% CI, 0.016 to 0.031 mPa.s, P < .001) during summer. After adjustment for age, cholesterol, smoking, blood pressure, body mass index, and years of education, mean differences decreased but still remained substantial and statistically significant (0.010 mPa.s; 95% CI, 0.003 to 0.018 mPa.s [P = .009] for winter activity; and 0.010 mPa.s; 95% CI, 0.002 to 0.017 mPa.s [P = .011] for summer activity). Similar results were found in women. WA showed no appreciable association with plasma viscosity after controlling for the covariates. CONCLUSIONS LTPA is inversely associated with plasma viscosity, independent of other risk factors, whereas WA shows no material effect in men and women. Decreased plasma viscosity may represent one mechanism through which LTPA confers a decrease of CHD risk.

Association between rheology and components of lipoproteins in human blood. Results from the MONICA project.

BackgroundRecent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies. Methods and ResultsWe studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25–64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r=0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r=−0.14/−0.10) and with apoprotein A-I (r=−0.08/−0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin. ConclusionsWe conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study.

Is Increased Plasma Viscosity A Risk Factor for High Blood Pressure

Data from several epidemiologic studies have suggested that, among other variables, hematocrit and fibrinogen may constitute risk factors for high blood pressure. As part of a population survey for cardiovascular risk factors, plasma viscosity and hemoglobin were measured. Blood pressure was determined under standardized conditions according to the recommendations of the AHA. A two- stage age-sex-stratified cluster sample of 5,312 persons, aged twenty-five to sixty-four years, was selected from a mixed urban/rural target population of 282,279 (total population approximately 533,000). A net response of 79.3% was achieved. Multiple logistic regression analyses including plasma viscosity, hemoglobin, body mass index, alcohol consumption, smoking behavior, and total serum cho lesterol as independent variables were run controlling for both age and sex. Plasma viscosity appeared as a significant main effect in all analyses and dem onstrated the strongest association with high blood pressure next to body mass index. Whether this association implies a causal relationship cannot be an swered from cross-sectional data. However, even if plasma hyperviscosity rep resents a secondary phenomenon in hypertension, it might be of prognostic relevance. There is evidence that increased plasma viscosity may contribute to myocardial hypertrophy. Therefore hypertensives with impaired blood fluidity might constitute a subgroup at particular risk for cardiovascular complications. When antihypertensive drugs are selected, their influence on blood viscosity should be taken into account.

Hemodynamic effects of alinidine st 567 at rest and during exercise in patients with chronic congestive heart failure

Selective inhibition of sinus node function offers the possibility to decrease heart rate and reduce myocardial oxygen consumption in patients with impaired cardiac function, if myocardial contractility is not further attenuated. To study the influence of a specific sinus node inhibitor on myocardial function, alinidine was given to 10 patients with chronic congestive heart failure and stable sinus rhythm. Radionuclide ventriculography was used to monitor left ventricular function at rest and during a standardized exercise protocol. After a bolus injection of 45 mg of alinidine followed by infusion of 10 mg/hr, radionuclide studies were repeated 1.5 and 3 hours later. The results show that left ventricular ejection fraction, stroke volume, and end-diastolic volume index were essentially unchanged, whereas cardiac index decreased by 10% at rest and during exercise. Heart rate decreased markedly by 14% at rest and by 13% during exercise. Systolic blood pressure was reduced by 6% at rest and by 14% during exercise. As a result of the marked decrease of these two parameters, a pronounced effect was seen on rate-pressure product with a 19% decrease at rest and a 24% decrease during exercise. No significant side effects were observed. Alinidine might be given to patients with chronic congestive heart failure and sinus rhythm in doses up to 45 mg without exerting a clinically relevant negative inotropic effect. Therefore it may represent an alternative to other drugs when a decrease in heart rate is desired to reduce myocardial oxygen consumption.

Noninvasive Detection of Anterior Wall Asynergies by Cardiokymography Compared to Electrocardiography

In order to determine the value of cardiokymography in detecting left ventricular (LV) anterior wall asynergies, 80 consecutive patients had a cardiokymogram (CKG) and an electrocardiogram (ECG) on the day prior to coronary angiography. Technically adequate CKGs were obtained in 72 patients (67 men and 5 women, mean age 53 +/- 6.5 years). For validation of regional contraction abnormalities, quantitative LV angiography was used. Stepwise linear discriminant analysis was applied to investigate the diagnostic power of CKG. Sensitivity of the CKG for LV anterior wall asynergy was 67.9% (ECG: 39.6%) and specificity was 68.4% (ECG: 94.7%) on the basis of 1 SD of the mean values of the radial axis shortening of a control group. For 2 SD, the sensitivity was 65.6% (ECG: 56.3%) and the specificity 47.5% (ECG: 90%). By combined testing, the specificity increased to 98.3%, whereas the sensitivity dropped to 26.9%. The improvement of the post-test likelihood for a positive ECG by a positive CKG is especially pronounced in the intermediate prevalence range, whereas for a negative ECG the post-test likelihood can be further decreased by a negative CKG in the intermediate and high prevalence range. The ECG as a single test seems to be the more appropriate noninvasive method for detecting LV anterior wall asynergies; however, the combined use of both ECG and CKG may considerably improve the diagnostic accuracy.

Behandlung von fehlenden Werten in den Statistik-Programmsystemen BMDP, SAS und SPSSx

Als wir gebeten wurden, auf der 28. Jahrestagung der GMDS etwas zum Thema ‘Fehlende Werte in Statistik-Programmsystemen’ vorzutragen, sagten wir zu, weil wir aus der taglichen Erfahrung im Umgang mit Statistikpaketen und ihren Benutzern wissen, das es da immer knifflige Probleme gibt, und deshalb uberzeugt waren, daruber etwas einigermasen Interessantes sagen zu konnen. Naturlich musten wir das Thema erst einmal eingrenzen und auf die bei uns hauptsachlich verwendeten Pakete beschranken, namlich BMDP, SAS und das neue SPSSx. Wir beabsichtigten, zunachst die informatischen Aspekte des Themas abzuhandeln, die Benutzern erstaunlich oft Schwierigkeiten machen. Dazu gehort, wie man in den Daten fehlende Werte in der einen oder anderen Weise kennzeichnen kann, was die genannten Pakete mit diesen Codes beim Einlesen der Daten machen, was mit den fehlenden Werten bei Datenmodifizierungen geschieht, wie sie dabei vielleicht erst neu entstehen usw. Dann wollten wir als Statistiker zu der uns besonders interessierenden Seite des Problems kommen, namlich der statistischen Behandlung fehlender Werte, d.h. der Frage, was die Pakete mit diesen Lochern in den Daten bei der Berechnung von Funktionen wie Verteilungsparameter, Teststatistiken, Modellen usw. tun.