Paul Knekt

Flavonoid intake and coronary mortality in Finland: a cohort study

Abstract Objective: To study the association between dietary intake of flavonoids and subsequent coronary mortality. Design: A cohort study based on data collected at the Finnish mobile clinic health examination survey from 1967-72 and followed up until 1992. Settings: 30 communities from different parts of Finland. Subjects: 5133 Finnish men and women aged 30-69 years and free from heart disease at baseline. Main outcome measure: Dietary intake of flavonoids, total mortality, and coronary mortality. Results: In women a significant inverse gradient was observed between dietary intake of flavonoids and total and coronary mortality. The relative risks between highest and lowest quarters of flavonoid intake adjusted for age, smoking, serum cholesterol concentration, blood pressure, and body mass index were 0.69 (95% confidence interval 0.53 to 0.90) and 0.54 (0.33 to 0.87) for total and coronary mortality, respectively. The corresponding values for men were 0.76 (0.63 to 0.93) and 0.78 (0.56 to 1.08), respectively. Adjustment for intake of antioxidant vitamins and fatty acids weakened the associations for women; the relative risks for coronary heart disease were 0.73 (0.41 to 1.32) and 0.67 (0.44 to 1.00) in women and men, respectively. Intakes of onions and apples, the main dietary sources of flavonoids, presented similar associations. The relative risks for coronary mortality between highest and lowest quarters of apple intake were 0.57 (0.36 to 0.91) and 0.81 (0.61 to 1.09) for women and men, respectively. The corresponding values for onions were 0.50 (0.30 to 0.82) and 0.74 (0.53 to 1.02), respectively. Conclusion: The results suggest that people with very low intakes of flavonoids have higher risks of coronary disease. Key messages Key messages The protective effect of flavonoids was associated with a diet high in intake of apples and onions The effect may be mediated through prevention of oxidation of low density lipoproteins but other mechanisms could be involved Flavonoids offer an explanation for the suggested beneficial effect of fruits and vegetables in coronary heart disease Further studies should concentrate on the effects of various flavonoid compounds and on populations with different intakes

Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies

BACKGROUND Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. OBJECTIVE We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. DESIGN This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. RESULTS During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. CONCLUSION The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.

Surgical or nonoperative treatment for lumbar spinal stenosis? A randomized controlled trial.

Study Design. A randomized controlled trial. Objectives. To assess the effectiveness of decompressive surgery as compared with nonoperative measures in the treatment of patients with lumbar spinal stenosis. Summary of Background Data. No previous randomized trial has assessed the effectiveness of surgery in comparison with conservative treatment for spinal stenosis. Methods. Four university hospitals agreed on the classification of the disease, inclusion and exclusion criteria, radiographic routines, surgical principles, nonoperative treatment options, and follow-up protocols. A total of 94 patients were randomized into a surgical or nonoperative treatment group: 50 and 44 patients, respectively. Surgery comprised undercutting laminectomy of the stenotic segments in 10 patients augmented with transpedicular fusion. The primary outcome was based on assessment of functional disability using the Oswestry Disability Index (scale, 0–100). Data on the intensity of leg and back pain (scales, 0–10), as well as self-reported and measured walking ability were compiled at randomization and at follow-up examinations at 6, 12, and 24 months. Results. Both treatment groups showed improvement during follow-up. At 1 year, the mean difference in favor of surgery was 11.3 in disability (95% confidence interval [CI], 4.3–18.4), 1.7 in leg pain (95% CI, 0.4–3.0), and 2.3(95% CI, 1.1–3.6) in back pain. At the 2-year follow-up, the mean differences were slightly less: 7.8 in disability (95% CI, 0.8–14.9) 1.5 in leg pain (95% CI, 0.3–2.8), and 2.1 in back pain (95% CI, 1.0–3.3). Walking ability, either reported or measured, did not differ between the two treatment groups. Conclusions. Although patients improved over the 2-year follow-up regardless of initial treatment, those undergoing decompressive surgery reported greater improvement regarding leg pain, back pain, and overall disability. The relative benefit of initial surgical treatment diminished over time, but outcomes of surgery remained favorable at 2 years. Longer follow-up is needed to determine if these differences persist.

Serum vitamin D and subsequent occurrence of type 2 diabetes.

Background: Low vitamin D status has been suggested as a risk factor for type 2 diabetes. Although the epidemiologic evidence is scarce, 2 recent studies have suggested an association. The present study investigated the relation of serum vitamin D with type 2 diabetes incidence using pooled data from these 2 cohorts. Methods: Two nested case-control studies, collected by the Finnish Mobile Clinic in 1973–1980, were pooled for analysis. The study populations consisted of men and women aged 40–74 years and free of diabetes at baseline. During a follow-up period of 22 years, 412 incident type 2 diabetes cases occurred, and 986 controls were selected by individual matching. Serum vitamin D (serum 25(OH)D) was determined from frozen samples, stored at baseline. Pooled estimates of the relationship between serum vitamin D concentration and type 2 diabetes incidence were calculated. Results: Men had higher serum vitamin D concentrations than women and showed a reduced risk of type 2 diabetes in their highest vitamin D quartile. The relative odds between the highest and lowest quartiles was 0.28 (95% confidence interval = 0.10–0.81) in men and 1.14 (0.60–2.17) in women after adjustment for smoking, body mass index, physical activity, and education. Conclusions: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association.

Determinants of sciatica and low-back pain

Several factors were studied for their association with the prevalence of chronic low-back syndromes, sciatica, and unspecified low-back pain (LBP) in 2,946 women and 2,727 men (age range, 30-64 years) participating in the Mini-Finland Health Survey, a project aimed at comprehensive evaluation of the populations health. On the basis of a standardized clinical examination, a physician diagnosed sciatica in 5.1% and LBP in 11.6% of the subjects. Those with a previous traumatic back injury had a 2.5-fold risk of having sciatica or LBP. The fractions of sciatica and LBP attributable to such back injuries were estimated to be 16.5% and 13.7%, respectively. Sum indices of both physical and mental stress at work were found to be directly proportional to the prevalence of sciatica and LBP. Smokers had an increased risk of LBP, and body height was related positively to the prevalence of sciatica. These associations, however, were inconsistent between sex and age subgroups. In the presence of osteoarthritis in the knee, hip, or hand, LBP was prevalent (adjusted odds ratio [OR], 5.3; 95% confidence interval [CI], 4.1-6.9), but sciatica was not (OR, 1.1; 95% CI, 0.7-1.7). Diabetics were found to have a significantly decreased prevalence of LBP (OR, 0.4; 95% CI, 0.3-0.8). Many factors, independent of each other, determine the occurrence of chronic low-back syndromes. The determinants of sciatica and LBP are different to some extent.

Depression and cardiovascular diseases

We first review the asSociations between depression and cardiovascular diseases (CVDs). Then we examine them in the nationally representative Mini‐Finland Health Survey, which covers 8,000 persons. Chronic somatic diseases and mental disorders were diagnosed using standardized methods. Cross‐sectionally, CVDs and neurotic depression were asSociated both before and after adjustment for covariates. The strongest asSociations were observed in the case of severe CVDs. During a 6.6 year follow‐up, the risk of CVD death and coronary death was elevated in depressed persons both with and without CVDs at entry. Much of the cross‐sectional asSociation is probably due to depression caused by CVDs. The outcome of CVD may be poorer in depressed persons. The hypothesis that depression is a cause of CVDs requires further study.

Risk of colorectal and other gastro‐intestinal cancers after exposure to nitrate, nitrite and N‐nitroso compounds: a follow‐up study

N‐nitroso compounds are potent carcinogens detected in foodstuffs. The importance of dietary nitrosamines in relation to human cancer development is, however, uncertain. We studied the relationship between intake of nitrates, nitrites and N‐nitrosodimethylamine (NDMA) and risk of cancers of the gastro‐intestinal tract in a cohort of 9,985 adult Finnish men and women. During a follow‐up period of up to 24 years, 189 gastro‐intestinal cancer cases were diagnosed in the cohort, initially free from cancer. Intake of nitrate, nitrite and NDMA were estimated, based on food‐consumption data from a 1‐year dietary history interview covering the total diet of the participants. A significant positive association was observed between intake of NDMA and subsequent occurrence of colorectal cancer with a relative risk (RR) between the highest and lowest quartiles of intake of 2.12 [95% confidence interval (CI) 1.04–4.33]. Of various sources of N‐nitroso compounds, intake of smoked and salted fish was significantly (RR = 2.58, 95% CI 1.21 − 5.51) and intake of cured meat was non‐significantly (RR = 1.84, 95% CI 0.98– 3.47) associated with risk of colorectal cancer. No similar association was observed for intake of other fish or other meat. No significant associations were observed between NDMA intake and cancers of the head and neck combined or of the stomach or between nitrate or nitrite intake and risk of cancers of the gastro‐intestinal tract. Our results are in line with the idea that N‐nitroso compounds can induce colorectal cancer in humans. Int. J. Cancer 80:852–856, 1999.

Vitamin D Status and the Risk of Cardiovascular Disease Death

Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases. The authors aimed to investigate whether serum 25-hydroxyvitamin D (25(OH)D) level predicts mortality from cardiovascular disease (CVD). The study was based on the Mini-Finland Health Survey and included 6,219 men and women aged > or =30 years who were free from CVD at baseline (1978-1980). During follow-up through 2006, 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified. Levels of 25(OH)D were determined from serum collected at baseline. Coxs proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death. After adjustment for potential confounders, the hazard ratio for total CVD death was 0.76 (95% confidence interval (95% CI): 0.60, 0.95) for the highest quintile of 25(OH)D level versus the lowest. The association was evident for cerebrovascular death (hazard ratio = 0.48, 95% CI: 0.31, 0.75) but not coronary death (hazard ratio = 0.91, 95% CI: 0.70, 1.18). A low vitamin D level may be associated with higher risk of a fatal CVD event, particularly cerebrovascular death. These findings need to be replicated in other populations. To demonstrate a causal link between vitamin D and CVD, randomized controlled trials are required.

Intake of dairy products and the risk of breast cancer

The relationship between intake of dairy products and risk of breast cancer was studied in 4697 initially cancer-free women, aged 15 years or over. During a 25 year follow-up period after the collection of food consumption data, 88 breast cancers were diagnosed. Intakes of foods were calculated from dietary history interviews covering the habitual diet of examinees over the preceding year. There was a significant inverse gradient between milk intake and incidence of breast cancer, the age-adjusted relative risk of breast cancer being 0.42 (95% confidence interval=0.24-0.74) between the highest and lowest tertiles of milk consumption. The associations with respect to other dairy products were not significant. Adjustment for potential confounding factors, i.e. smoking, body mass index, number of childbirths, occupation and geographic area, resulted in only a minor change in the milk intake-breast cancer relation. Nor did adjustment for intake of other foodstuffs and nutrients, e.g. energy, carbohydrates, protein, fat, vitamins and trace elements, alter the results. No significant interactions between milk intake and demographic or dietary variables or time of cancer diagnosis were observed. Our data suggest that there is a protective effect, dietary or habitual, associated with consumption of milk that overwhelms the associations between different other factors and risk of breast cancer.

Risk of disability and mortality due to overweight in a Finnish population.

OBJECTIVE--To investigate the effect of overweight on premature mortality and work disability in young and middle aged Finns. DESIGN--Prospective cohort study based on data collected in the multiphasic health examinations by the Social Insurance Institution of Finland from 1966 to 1972 and follow up until 1982. SETTING--34 Communities throughout Finland. SUBJECTS--12,053 Women and 19,076 men who were employed and aged 25-64 at baseline. MAIN OUTCOME MEASURES--Mortality and work disability pensions from all and specified causes. RESULTS--Body mass index was a weak predictor of death but a strong predictor of early work disability, which increased linearly with body mass index. After adjustment for age, geographical region, occupation, and smoking the relative risks of work disability for women and men with a body mass index greater than or equal to 30 kg/m2 were, respectively, 2.0 (95% confidence interval 1.8 to 2.3) and 1.5 (1.3 to 1.7) when compared with those of subjects with body mass index less than 22.5 kg/m2. The increased risks were due to an excess of cardiovascular and musculoskeletal diseases but not of mental diseases. One fourth of all disability pensions from cardiovascular and musculoskeletal causes in women and half as many in men could be attributed to overweight (body mass index greater than 25 kg/m2) alone. CONCLUSIONS--Though modest overweight has little impact on mortality it predicts severe functional impairment. A considerable proportion of work disability pensions could probably be prevented by efficient weight control.