Hans W. Hense

Plasma fibroblast growth factor 23, parathyroid hormone, 25-hydroxyvitamin D3, and risk of heart failure: a prospective, case-cohort study.

CONTEXT Bone mineral metabolism may play a role in the development of heart failure (HF). OBJECTIVE The aim of the study was to investigate the relationships of plasma fibroblast growth factor (FGF) 23, PTH, and 25-hydroxyvitamin D3 [25(OH)D3] with incident congestive HF in a population-based cohort of men and women aged 40-65 and 35-65 years, respectively, at baseline. DESIGN We conducted a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, including a randomly drawn sample of the total cohort free of HF and all incident HF cases that occurred during a mean follow-up of 8.2 ± 1.6 years. PARTICIPANTS AND SETTING A total of 221 incident congestive HF cases and 1228 individuals free of HF were included in the study. MAIN OUTCOME MEASURES Incident congestive HF was measured. RESULTS In a multivariable model, each doubling of FGF23 [ie, per log (base 2) unit higher FGF23] was associated with a 29% higher HF risk (hazard ratio, 1.29 [95% confidence interval (CI), 1.07-1.56]). After multivariable adjustment, including estimated glomerular filtration rate, PTH was not related to HF risk (hazard ratio per doubling of PTH, 1.21 [95% CI, 0.99-1.48]). However, an interaction was observed between PTH and obesity, suggesting a relationship with HF risk in obese, but not in nonobese individuals. The hazard ratio for HF per doubling of 25(OH)D3 was 1.02 (95% CI, 0.73-1.41). CONCLUSIONS Our findings provide epidemiological evidence for a positive relationship between FGF23 and risk of HF. The role of PTH in the development of HF remains unclear, in particular in obese individuals, until further confirmation in other studies. 25(OH)D3 was not related to HF.

The Association of Blood Lead and Blood Pressure in Population Surveys

Several reports from large population surveys have indicated that blood lead is positively related to blood pressure. We assessed this relation in 1,703 men (median blood lead = 83

Associations Between Homocysteine and Coagulation Factors — A Cross-Sectional Study in Two Populations of Central Europe

mUg per liter) and 1,661 women (median blood lead = 60

The association of antihypertensive treatment patterns and adverse lipid effects in population-based studies

mUg per liter), age 28 to 67 years, who participated in the first follow-up examination of the MONICA Augsburg cohort study in 1987–1988. Crude analyses confirmed a strong, positive association of blood lead concentrations with systolic and diastolic blood pressure. We identified age, body mass index, hematocrit, and alcohol consumption as the quantitatively most important confounders of this association. Adjustment for these variables, in particular for hematocrit and alcohol consumption, considerably reduced the magnitude of the blood lead effect on blood pressure. There were no indications for marked nonlinearity or threshold effects. After control of confounders, a difference of 100

Relationship between N-Terminal Pro-Brain Natriuretic Peptide, Obesity and the Risk of Heart Failure in Middle-Aged German Adults

mUg per liter in blood lead levels, corresponding to rather extreme positions in the lower and upper end of the population blood lead distribution, related to estimated blood pressure increases of less than 3 mmHg. The appropriateness of treating hematocrit and alcohol consumption as confounders of the blood lead-blood pressure relation is discussed on the basis of current pathophysiologic concepts. We conclude that hematocrit should always be taken into account as a relevant confounder. On the other hand, the interrelation of alcohol consumption, blood lead, and blood pressure is presently not clearly understood; that is, its appropriate analytic handling cannot be determined. The consequences of these considerations on estimates of the blood lead effect on blood pressure may be both over- and underestimations.

Alcohol consumption as a modifier of the relation between blood lead and blood pressure.

Plasma homocysteine has been associated with vascular disease and mortality. Experimental studies and studies on patients with vascular disease have indicated a thrombogenic potential of raised homocysteine levels. Studies on community samples are rare. We investigated the associations between homocysteine levels and selected coagulation factors in population-based random samples of 187 men from Pardubice (Czech Republic) and 147 men from Augsburg (Germany), aged 45 to 64 years. Czech men had higher mean levels of plasma homocysteine (10.3 vs. 8.9 micromol/l, P<.001) and of fibrinogen, von Willebrand factor (vWF), prothrombin fragment 1+2 (F 1+2) and D-Dimer (each P<.05). Plasma homocysteine was positively correlated with fibrinogen (r=.34) and vWF (r=.23, each P<.001) only in Czechs, and with D-Dimer in both Czechs and Germans (r=.26 and.21, respectively). Formal testing for interaction regarding the intercountry differences in the relationship with homocysteine revealed significance only for fibrinogen (P<.01). In multivariate analyses, the association of homocysteine with D-Dimer remained statistically significant after adjustment for indicators of chronic inflammation and fibrinogen. No significant correlation was found with Factor VII (F VII) activity or F 1+2. Homocysteine levels were also unrelated to traditional risk factors. In conclusion, in these cross-sectional studies we found moderate to strong associations between homocysteine and components of the endogenous hemostatic and fibrinolytic systems. The associations were slightly different between Czech and German men. These findings may help to better understand the role of homocysteine in atherothrombotic diseases.

Central pulse pressure and augmentation index in asymptomatic bicuspid aortic valve disease

We investigated the relationship between antihypertensive drug treatment of hypertensives and their mean serum lipid concentrations in population based studies in Germany. Data from three surveys (Luebeck Blood Pressure Study (LBS) of 1984, MONICA Augsburg Survey I of 1984/85, MONICA Augsburg Survey II of 1989/90), obtained on random samples of the population aged 25-64 years, were used for cross-sectional analyses. Moreover, prospective analyses were carried out on participants of the MONICA Augsburg cohort study of 1987/88 (3-year-follow-up of the MONICA Survey I). Blood pressure, non-fasting serum total cholesterol and HDL-cholesterol, and body height and weight were measured under strictly standardized conditions. Interview data were available on medical history including medication use, and on smoking and alcohol consumption. In cross-sectional and prospective analyses treated male and female hypertensives in each population had significantly lower crude mean HDL-C concentrations than untreated hypertensives, borderliners, or normotensives. Differences in mean HDL-C between untreated and treated hypertensives were attenuated but still significant after control of confounders and ranged from 1.8 to 6.1 mg/dl (i.e. in relative terms, -3.4 to -12.9%) in men and from 3.6 to 9.4 mg/dl (-5.7 to -14.9%) in women. By contrast, crude and multivariate associations of antihypertensive treatment with non-HDL-C (total minus HDL-C) levels were inconsistent and not significant. The inverse association of drug therapy with HDL-C was confirmed by prospective analyses in the MONICA cohort study supporting a causal relationship. Treatment patterns in a community (prevalence of prescribed drug classes) correlated with the magnitude and significance of HDL-C effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Screening for Hypertension

Background Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status. Methods A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years) and heart failure cases outside the sub-cohort (n = 197). Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2). Results Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR) and 95% confidence interval (CI): 2.56 (1.49–4.41) for the top versus bottom tertile of NT-proBNP, ptrend:<0.01). In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI) from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85–3.49), 2.72 (1.42–5.22), and for obese: 3.29 (1.04–10.40), reference, 3.74 (1.52–9.21). Conclusions Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms.

Left-ventricular dysfunction.

Hypothetically, blood lead may be involved in blood pressure elevations owing to a facilitation of vascular adrenergic stimulation by extrinsic factors like alcohol. We therefore investigated whether self-reported alcohol consumption was a modifier of the blood lead-blood pressure relation in 3,664 men and women, age 28-67 years, from the MONICA Augsburg study in Germany. In women, only heavy drinkers (40 gm alcohol per day or more) showed a strong relation of blood lead with systolic and diastolic blood pressure, whereas little association was observed for abstaining and for moderately drinking women. In men, we found similar alcohol modifications of the lead-pressure relation only for those with rural, rather than urban, places of residence. We have no explanation for this subgroup divergence. Our results may be taken to indicate a possible role of alcohol consumption in modifying the action of lead on blood pressure.

An ecological study of determinants of coronary heart disease rates: a comparison of Czech, Bavarian and Israeli men.

a Centre of Cardiology and Cardiovascular Surgery, University Hospital Eppendorf, Hamburg, Germany b Department of Medical Biometry and Epidemiology, University Hospital Eppendorf, Hamburg, Germany c Medical Clinic II, University of Lubeck, Germany d Institute of Epidemiology and Social Medicine, University of Muenster, Germany e Helmholtz Zentrum Munchen, German Research Center for Environmental Health (GmbH), Institute of Epidemiology II, Neuherberg, Germany f Institute of Medical Genetics, Charite Universitatsmedizin Berlin, Germany