Category Archive for: ‘Disease outcomes’
Genotype apolipoprotein E4 (APOE4) associated with cognitive decline
The Zutphen Elderly Study showed that the risk of cognitive decline over three years was 3 times greater among the carriers of an isoform (certain variety of the genotype apolipoprotein E) called APOE4, compared to that of non-carriers.
Synergistic effect of genotype APOE4 and stroke on cognitive decline
Carriers of APOE4 without stroke had a 3 times greater risk of cognitive decline; non-carriers with stroke had a 5 times greater decline and those with both risk factors had a 17 times greater risk of decline.
Cognitive decline is a potential risk factor for reduced cognitive functioning. The genetic heterogeneity of apolipoprotein E may be involved in the etiology of familial Alzheimer disease. The apolipoprotein E polymorphism affects serum lipoprotein levels and the APOE4 isoform is increased in Alzheimer disease.
Cardiovascular risk factors also associated with dementia
The risk factors – smoking, serum cholesterol, blood pressure, lung function and the presence of CVD at baseline – were associated with death from dementia. The risk was 58% greater for heavy compared to non-smokers, 55% greater for hypertensives compared to those with normal blood pressure, 73% greater for those with a high level of serum cholesterol, 46% lower for those with a high compared to a low lung function and 94% greater for those with a history of CVD at baseline compared to those with no such history. Men with a combination of two of the risk factors had a 2 times greater risk of death from dementia. These results suggest that that cardiovascular risk factors measured in midlife predict the risk of death with dementia.
Cardiovascular risk factors measured in the Seven Countries Study
Cardiovascular risk factors were measured at baseline and 160 out of 10,211 middle-aged men died from dementia during 40 years of follow-up. The results of the SCS suggest that cardiovascular risk factors affect the neurodegenerative process leading to dementia.
Low alcohol intake associated with low all-cause mortality and better survival
Among regular consumers of alcoholic beverages in the Zutphen Study, average alcohol intake increased from 8 g/d in 1960 to 18 g/d in 1985 and then decreased to 13 g/d in 2000. All-cause mortality during 40 years of follow-up was 25% lower in men who drank less than 20 g alcohol per day and on average 6 g/d compared to non-drinkers. Men average aged 50 with a long-term regular alcohol intake of 20 g/d or less, had a 2.3 years longer life expectancy than those who did not use alcohol.
Wine drinkers had the best life expectancy
The life expectancy of wine drinkers (average age 50, average alcohol intake 2 g/d) was 4.7 years longer compared to those who did not use alcohol. For those who consumed on average 8 g/d alcohol as beer or spirits the difference in life expectancy from non-alcohol drinkers was 2.2 years.
Strong relationship of smoking with all-cause mortality
Smoking was associated with all-cause mortality after 10-years of follow-up in all cohorts of the Seven Countries Study except the Japanese, apparently due to the small number of events in Japan in the early follow-up. The strength of this association was stronger in the cohorts from the US and northern Europe than in the eastern and southern European cohorts. After 25 years of follow-up, in contrast, smoking was associated with a higher all-cause mortality in all 16 cohorts. For example, the 40-year follow-up data from the Zutphen Study showed that smokers had a 60% higher all-cause mortality compared to non-smokers. In the elderly men of Finland, the Netherlands and Italy, the 10-year all-cause mortality was 67% higher in smokers than in non-smokers.
Apparent large health gain from stopping smoking
Men who stopped smoking at age 40 had 4.6 year greater life expectancy, while men who stopped smoking at age 70 had an addes 2.5 years. Life expectancy at age 40 was 6.8 years shorter for cigarette smokers compared to non-smokers and 8.8 years for men who smoked more than 30 cigarettes per day. Exclusively cigar or pipe smokers had a 4.7 year lower life expectancy.
- Keys et al. Harvard University Press. ISBN 0-674-80273-3, 1980: 136-60
- Jacobs et al. Arch Intern Med 1999;159:733-40
- Menotti et al. Eur Heart J 2001;22:573-9
- Streppel et al. Tob Control 2007;16:107-13
Activity inversely related to all-cause mortality
Elderly men in Zutphen with a high level of leasure physical activity (mean 1217 min/week) had a 23% lower all-cause mortality after 10 years of follow-up compared to those with a low level (mean 122 min/week). Men who walked or cycled at least 3 times per week for 20 min or more per day were called active and those who did not meet the criterion were considered sedentary. All-cause mortality was 29% lower in the active compared to the sedentary men.
Reducing activity was associated with greater all-cause mortality
Changes in physical activity over the period of study were also related to all-cause mortality rate. Men who were sedentary in both 1985 and 1990 surveys had a 2 times greater risk of death from all-causes by 1995 compared to those who were classed as active in both surveys. A gradient of decreasing risk of death was observed among those who became active compared to those who became or remained sedentary.
Measuring physical activity
In the Zutphen Elderly Study physical activity was assessed with a questionnaire among these retired men, which queried about frequency and duration of walking, cycling, sports, gardening, hobbies and odd jobs. The questionnaire was validated against measures of total energy expenditure.
- Caspersen et al. Am J Epidemiol 1991;133:1078-92
- Bijnen et al Arch Intern Med 1998;158:1499-1505
- Bijnen et al. Am J Epidemiol 1999;150:1289-96
Healthy diet associated with low all-cause mortality
A Healthy Diet Indicator (HDI) score was calculated based on the 1990 Guidelines of WHO on prevention of chronic diseases for men aged 50-70 from Finland, The Netherlands and Italy. The 20-year all-cause mortality was 13% lower in the group with the highest compared to the lowest HDI.
Mediterranean diet related to low all-cause mortality
In the HALE project the Mediterranean Diet Score (MDS) was associated with a 18% lower and the Mediterranean Adequacy Index (MAI) with a 17% lower 10-year all-cause mortality. The MDS and the MAI were both based on foods characteristic of the traditional Mediterranean diet in the 1960s. Within these dietary patterns, grains, fruit and fish were most strongly and inversely related to all-cause mortality.
All three scores indicated that a healthy dietary pattern is associated with a lower all-cause mortality.
The lignan MAT might be inversely related to CHD
The median total lignan intake in elderly men in Zutphen was 977 microgram/d. The intake of the lignan MAT (matairesinol) was significantly inversely related to 15-year fatal CHD – in contrast to the total lignan intake which was unrelated. The inverse association between MAT and CHD mortality could be due to an associated factor such as wine consumption.
How to measure lignans
Lignans are diphenolic compounds present in plant foods (and not to be confused with lignin, one of the dietary fibers). We studied the lignans LARI (lariciresinol), PINO (pinoresinol), SECO (secoisolariciresionol) and MAT. These molecules are converted to enterolignans by the intestinal microflora and possess estrogen-like activities.
We developed a method to measure the four lignans in foods and beverages. The most abundant lignan sources are flaxseed and sesame seeds. In the Zutphen Elderly Study most of the lignans came from tea, vegetables, bread, coffee, fruit and wine.
A Mediterranean style diet was consistently associated with lower cardiovascular risk
Adhering to a Mediterranean style diet was associated with a 39% lower coronary mortality risk and a 29% lower cardiovascular mortality risk in middle-aged and elderly European men and women in the HALE project. The Mediterranean diet score we used was based on eight basic food groups: bread, legumes, vegetables, fruit, fish, fats, dairy products and meats. A high intake of bread, legumes, vegetables, fruit and fats rich in unsaturated fatty acids, a moderate intake of fish and a low intake of dairy and meat was characteristic of a Mediterranean diet.
Measuring habitual diets
The HALE project dealt with European elderly men and women participating in the FINE and the SENECA Studies. They were 70-90 years old at baseline and were followed for 10 years. In both studies the dietary history was recorded as the measure of habitual food consumption.
CVD Main topics
High cohort flavonol intake related to low CHD mortality rates.
The intake of flavonols
Information on the average food intake of the 16 cohorts was obtained in the 1960s, and the average flavonol intake was determined chemically in representative food composites. The most common flavonol measured was quercetin. Flavonols are a subclass of the flavodnoids, an extended class of chemically related compounds ubiquitously present in plant foods. In a range of experimental models, these compounds have demonstrated biological effects, which may partially explain the beneficial health effects of a diet high in vegetables and fruits. Flavonols are present in tea, apples, onions and red wine. High intakes were observed in Japan due to a high consumption of tea, in Slavonia (Croatia) due to a high intake of onions and in Dalmatia (Croatia) because of a high intake of red wine.
A high saturated fat intake, a low flavonoid intake and smoking are associated with high CHD mortality rates
Three factors combined – saturated fat, flavonoids and smoking – account for 90% of the differences in 25-year CHD mortality rates among the 16 cohorts in the Seven Countries Study. In univariable models average saturated fat intake at baseline was strongly associated with CHD mortality, while average flavonoid intake was inversely related. The prevalence of smoking at baseline was not related to CHD mortality rates. However, multivariable modeling showed that saturated fat and smoking were positively and that flavonoid intake was inversely related to CHD mortality rates.
Interpretation of the results
Based on mechanistic studies confirming these associations we conclude that saturated fat increases the cholesterol rich LDL-lipoprotein fraction and the risk of atherosclerosis. Smoking promotes LDL oxidation that might be offset by the strong antioxidant effects of flavonoids. Trials showed that replacing saturated with polyunsaturated fat reduces CHD risk. Prospective cohort studies found that stopping smoking and a high intake of flavonoids are associated with a lowered CHD risk. These results found at the population level in the Seven Countries Study are thus in agreement with those obtained in experimental and prospective cohort studies, strenghtening the interpretation of cause and prevention.