Jarmo Virtamo

Different Risk Factors for Different Stroke Subtypes Association of Blood Pressure, Cholesterol, and Antioxidants

BACKGROUND AND PURPOSEnBlood pressure is an important risk factor for stroke, but the roles of serum total and HDL cholesterol, alpha-tocopherol, and beta-carotene are poorly established. We studied these factors in relation to stroke subtypes.nnnMETHODSnMale smokers (n=28 519) aged 50 to 69 years without a history of stroke participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a controlled trial to test the effect of alpha-tocopherol and beta-carotene supplementation on cancer. From 1985 to 1993, a total of 1057 men suffered from primary stroke: 85 had subarachnoid hemorrhage; 112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke.nnnRESULTSnSystolic blood pressure > or = 160 mm Hg increased the risk of all stroke subtypes 2.5 to 4-fold. Serum total cholesterol was inversely associated with the risk of intracerebral hemorrhage, whereas the risk of cerebral infarction was raised at concentrations > or = 7.0 mmol/L. The risks of subarachnoid hemorrhage and cerebral infarction were lowered with serum HDL cholesterol levels > or = 0.85 mmol/L. Pretrial high serum alpha-tocopherol decreased the risk of intracerebral hemorrhage by half and cerebral infarction by one third, whereas high serum beta-carotene doubled the risk of subarachnoid hemorrhage and decreased that of cerebral infarction by one fifth.nnnCONCLUSIONSnThe risk factor profiles of stroke subtypes differ, reflecting different etiopathology. Because reducing atherosclerotic diseases, including ischemic stroke, by lowering high serum cholesterol is one of the main targets in public health care, further studies are needed to distinguish subjects with risk of hemorrhagic stroke. The performance of antioxidants needs confirmation from clinical trials.

Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis

Background. Only a few reported studies focus on the natural history and course of advanced and severe chronic atrophic gastritis. Methods. In this study we followed 47 men (mean age 62 years) with advanced (moderate or severe) Helicobacter pylori‐positive atrophic corpus gastritis. Duration of endoscopic follow‐up was 6 years and follow‐up based on serum levels of pepsinogen I and antibodies to H. pylori covered a period of 10 years. None of the patients was treated for H. pylori infection prior to end of follow‐up. Results. The median H. pylori antibody titre declined (IgG from 4000 to 1300; IgA from 200 to 50) in the study population, and 11 men (23%) converted to seronegative (p=0.0005, Fishers exact test). There was a small but significant (p=0.0004, Pages test) declining trend in mean atrophy score of the corpus during follow‐up (from 2.5 to 2.2). However, no significant changes were observed in grade of atrophy or intestinal metaplasia of the antral mucosa or in grade of intestinal metaplasia in the corpus. The mean SPGI level remained at the initial low level during the entire follow‐up. Conclusions. H. pylori antibodies disappear spontaneously within 10 years in almost one fourth of patients with advanced atrophic corpus gastritis. The disappearance of H. pylori antibodies is accompanied by no or more than a mild improvement of the gastric mucosa.

High processed meat consumption is a risk factor of type 2 diabetes in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study

Relatively small lifestyle modifications related to weight reduction, physical activity and diet have been shown to decrease the risk of type 2 diabetes. Connected with diet, low consumption of meat has been suggested as a protective factor of diabetes. The aim of the present study was to examine the association between the consumption of total meat or the specific types of meats and the risk of type 2 diabetes. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort included middle-aged male smokers. Up to 12 years of follow-up, 1098 incident cases of diabetes were diagnosed from 24 845 participants through the nationwide register. Food consumption was assessed by a validated FFQ. In the age- and intervention group-adjusted model, high total meat consumption was a risk factor of type 2 diabetes (relative risk (RR) 1.50, 95 % CI 1.23, 1.82, highest v. lowest quintile). The result was similar after adjustment for environmental factors and foods related to diabetes and meat consumption. The RR of type 2 diabetes was 1.37 for processed meat (95 % CI 1.11, 1.71) in the multivariate model. The results were explained more by intakes of Na than by intakes of SFA, protein, cholesterol, haeme Fe, Mg and nitrate, and were not modified by obesity. No association was found between red meat, poultry and the risk of type 2 diabetes. In conclusion, reduction of the consumption of processed meat may help prevent the global epidemic of type 2 diabetes. It seems like Na of processed meat may explain the association.

Association of Seropositivity to Helicobacter Species and Biliary Tract Cancer in the ATBC Study

Helicobacter have been detected in human bile and hepatobiliary tissue. Despite evidence that Helicobacter species promote gallstone formation and hepatobiliary tumors in laboratory studies, it remains unclear whether Helicobacter species contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to 15 Helicobacter pylori proteins was associated with subsequent incidence of hepatobiliary cancers in the Finnish Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study. We included 64 biliary cancers, 122 liver cancers, and 224 age‐matched controls which occurred over the course of 22 years. Helicobacter pylori seropositivity was defined as those positive to ≥4 antigens. Odds ratios (OR) and 95% confidence intervals were adjusted for major hepatobiliary cancer risk factors. Among the controls, 88% were seropositive to H. pylori at baseline. Among those who subsequently developed hepatobiliary cancer, the prevalence of seropositivity was higher: 100% for gallbladder cancer, 97% of extrahepatic bile duct cancer, 91% of ampula of Vater cancer, 96% of intrahepatic bile duct cancer, and 94% of hepatocellular carcinoma. Although the OR for gallbladder cancer could not be calculated, the OR for the other sites were 7.01 (95% confidence interval [CI]: 0.79‐62.33), 2.21 (0.19‐25.52), 10.67 (0.76‐150.08), and 1.20 (0.42‐3.45), respectively, with an OR of 5.47 (95% CI: 1.17‐25.65) observed for the biliary tract cancers combined. ORs above 1 were observed for many of the investigated antigens, although most of these associations were not statistically significant. Conclusion: Seropositivity to H. pylori proteins was associated with an increased risk of biliary tract cancers in ATBC. Further studies are needed to confirm our findings and to determine how H. pylori might influence the risk of biliary tract cancer. (Hepatology 2014;60:1962–1970)

A prospective analysis of telomere length and pancreatic cancer in the alpha-tocopherol beta-carotene cancer (ATBC) prevention study

Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length maintenance. To test whether telomere length is associated with pancreatic cancer risk, we conducted a nested case–control study in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50–69 years at baseline. Between 1992 and 2004, 193 incident cases of pancreatic adenocarcinoma occurred (mean follow‐up from blood draw: 6.3 years) among participants with whole blood samples available for telomere length assays. For these cases and 660 controls, we calculated odds ratios (OR) and 95% confidence intervals using unconditional logistic regression, adjusting for age, number of years smoked regularly, and history of diabetes mellitus. Telomere length was categorized into quartiles (shortest to longest) and analyzed as both a categorical and a continuous normal variable (reported per 0.2 unit increase in telomere length). All statistical tests were two‐sided. Longer telomere length was significantly associated with increased pancreatic cancer risk (continuous OR = 1.26 95% CI = 1.09–1.46; highest quartile compared to lowest, OR = 1.57, 95% CI = 1.01–2.43, p‐trend = 0.007). This association remained for subjects diagnosed within the first five years of blood draw (continuous OR = 1.46, 95% CI = 1.19–1.79 highest quartile OR = 2.92, 95% CI = 1.47–5.77, p‐trend = 0.002), but not those diagnosed greater than five years after blood draw (continuous OR = 1.03, 95% CI = 0.85–1.22; highest quartile OR = 1.04, 95% CI = 0.60–1.79). This is the first prospective study to suggest an association between longer blood leukocyte telomere length and increased pancreatic cancer risk.