FSN 420 paper evaluation form cohort studies
Jessica Hews
Study: Journi Karppi, Jari A. Laukkanen, Juhani Sivenius, Kimmo Ronkainen, 2012.
Research Question:
 The researchers wanted to determine if there is a relationship between serum carotenoids and
ischemic stroke in men.
 The research question was clearly stated at the end of the introduction section
 There is no clearly stated hypothesis. The authors discussed previous studies finding a
relationship between carotenoids and a lower stroke risk, but findings from other studies were
proven to be inconsistent. However, the researchers do list a possible reason as to why a
specific carotenoid (lycopene) may decrease stroke risk, which they do analyze as part of their
results.
Design:
Men in the
Ischemic
Heart
Disease
Risk Factor
Cohort
Study
Free of disease or
condition of interest
(So exclude patients with
who have already had a
stroke)
PRESENT

Stroke
Consumed
many
carotenoids
No Stroke
Consumed
fewer
carotenoids
Stroke
No Stroke
FUTURE
The researchers chose men from the Kuopio Ischemic Heart Disease Risk Factor Study between
1991-1993. At the start of this study, blood samples were taken to determine serum carotenoid
concentration. The men were then put into categories of quartiles. The authors measured other
demographic characteristics such as BMI, alcohol consumption, and smoking habits. Diagnosis
and incidence of stroke was based on Kuopio hospital data and registry.
Subjects
 Men who were in the Kuopio Ischemic Heart Disease Risk Factor Study were selected to
participate.
 Inclusion criteria: subjects with no missing data
 Exclusion criteria: men who have already had a stroke
 These criteria were appropriate because of the nature of a prospective cohort study. The
participants should not have the disease of interest, and having a full data set for each subject
will provide a full analysis with accurate results
 Characteristics of the participants with or without a stroke were listed in Table 1. Table 2 listed
the demographics of the participants with no history of stroke based on lycopene quartiles.
 The sample was representative of the men living in Kuopio because of the large number of
subjects. But if the target population is men of all geographic locations, then the sample is not
representative of men as a whole.
 The sample size was n=1,013 men aged 46-65.
 The selection of study groups was free from bias because the men without any specific disease
were chosen. Since the researchers are looking at the incidence of disease over time, they
would have no way of knowing whom they should select to participate.
FSN 420 paper evaluation form cohort studies
Exposure(s):
 The exposures were antioxidants: lycopene, carotene, tocopherol, and retinol.
 The serum concentrations were separated by quartiles of carotenoids, as displayed in Table 3.
 The serum samples were taken in one sitting, and the median follow-up time was 12.1 years
after the baseline assessment
 The serum concentrations of all these antioxidants were measured by high performance liquid
chromatography
 Strengths: using a biomarker to assess intake is beneficial when it is difficult to determine
dietary data. There is less human judgment error, and it can also reflect absorption, metabolism,
and excretion
 Weaknesses: there may be unknown dietary elements in the foods besides carotenoids that
could be creating an effect
Outcome measure(s)
 Outcome: stroke
 Incidence of strokes between 1991 and 1992 was retrieved through the Monitoring of Trends
and Determinants in Cardiovascular Diseases (FINMONICA). For the incidence rates between
1993 and 1999, the data was obtained from the Finnish national hospital discharge registry and
death certificate registers. Diagnosis was based on FINMONICA criteria, which involved various
codes for each type of stroke. A CT scan and MRI was carried out on each participant by 1997 to
confirm a diagnosis.
 The median follow-up was 12 years, which appears to be long enough because these men came
from a disease Risk Factor Study and they are at an age where they are prone to these
incidences.
Subject Attrition
 Subject attrition was briefly mentioned at the end of the methods section. The researchers
stated that because every resident of Finland has a personal ID in the national hospital registry,
there were no dropouts to report.
Covariables and Confounders
 Confounders were considered in the data analyses, which included age, year of examination,
BMI, blood pressure, smoking, serum LDL cholesterol, diabetes, and history of stroke. The
researchers adjusted for these variables in their model, as stated in fine print below the data
tables.
 Missing confounders include: physical activity, alcohol use, and dietary data. Physical activity
and alcohol consumption were both measured using a frequency questionnaire, but they were
not included in the adjusted model. Dietary data was never mentioned as a potential
confounder. There may have been a food item or nutrient the Finnish men were consuming that
could affect antioxidant levels and/or their stoke risk.
Findings and Conclusions:
 The main results could be found in Tables 3 and 4. Table 3 listed the hazard ratios of any stroke
and Table 4 listed the results of ischemic stroke according to quartiles of carotenoids
 As shown in Table 3, there is a 55% decreased risk of any stroke in the highest carotenoid
quartile, which is >0.22micromol/L of serum lycopene. This result had a p-value of 0.036<0.05,
indicating statistical significance of a difference between the quartiles. There was no



FSN 420 paper evaluation form cohort studies
relationship between carotene, retinol, tocopherol and stroke risk because the results were not
statistically significant.
In Table 4, the results indicated that there is a 59% decreased risk of an ischemic stroke for men
in the highest quartile for serum lycopene (>22micromol/L). The p-value=0.042, indicating
statistical significance of a relationship between the exposure and outcome. Similar to Table 3,
there was no evidence of a relationship between an ischemic stroke and the serum
concentration of the other antioxidants.
There is external validity if the target population is Finnish men because the cohort only
involved men from that geographic location. But these results cannot be generalized to the
population of men as a whole because the sample only came from Kuopio.
The authors’ conclusions were supported by the results because they stated that only serum
lycopene indicated a significant decreased stroke risk for both categories, according to the
hazard ratios.
Overall Strengths:
 There is no selection bias because a prospective study looks at the incidence of a disease or
condition over time; therefore they are unaware of what condition and dietary exposure they
are examining beforehand.
 Since this is a study over a long period of time, multiple exposures can be collected and analyzed
 A variety of diseases as well as mortality rates can be easily assessed because of all the available
data.
Overall Limitations or Weaknesses, including limitations to establishment of a cause-effect
relationship:
 Since this was an observational study, the authors cannot make cause-and-effect conclusions;
they can only determine a relationship between the dietary exposure and health outcome.
Cause and effect conclusions can only be drawn from an experimental randomized control trial.
 Not all confounders can be accounted for because of all the data being collected
 The self-administered questionnaires for demographic characteristics may not be accurate (over
and underreporting).
 No dietary assessment tools were used to assess nutrient intake, which could have an effect on
the results