[The relationship between lack of educational attainment, cardiovascular risk factors, atherosclerosis and coronary artery disease].

INTRODUCTION: Educational attainment is related to improved health and longevity. We investigated the relationship between educational attainment and cardiovascular risk factors, subclinical atherosclerosis, and incidence of coronary artery disease. MATERIAL AND METHODS: The Reykjavik REFINE study is a population-based study recruiting 6616 subjects, 25-69 years of age from the greater Reykjavik area in 2005-2011. Baseline measurements of cardiovascular risk factors were performed, and all participants had a carotid ultrasound examination to detect subclinical atherosclerotic lesions. Clinical follow-up of cardiovascular disease during a ten-year period was performed. Educational attainment was related to clinical outcome measures. RESULTS: The study population comprised of 3251 men and 3365 women. The proportion of the study population with primary school education only was 20.1%, 31.2% had vocational training, 12.3% had high school education and 36.4% were university graduates. Traditional cardiovascular risk factors were generally higher among subjects with primary school education only. Compared to subjects with university education, the odds ratio of having severe atherosclerotic plaque was 1.84 (95% CI 1.40-2.43) among those with primary school education only and 1.49 (95% CI 1.16-1.91) among subjects with vocational training. The subjects with high school or university education were less likely to develop significant cardiovascular disease during the 10-year follow-up period. CONCLUSION: Primary school and vocational training compared to university education are associated with risk factors of atherosclerotic disease, subclinical carotid plaque, and incidence of cardiovascular disease. The reason for this disparity remains to be clarified but socioeconomic inequality related to less educational attainment might be involved.

Carotid plaque is strongly associated with coronary artery calcium and predicts incident coronary heart disease in a population-based cohort.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) and carotid plaque are markers of atherosclerosis and predict future coronary heart disease (CHD) events. The aim of this study was to investigate associations between CAC and carotid plaque in asymptomatic individuals, also in relation to predicted CHD-risk and incident events. A secondary aim was to compare predictive value between CAC, carotid plaque, and total carotid plaque area (TPA) as predictors for future CHD-events. METHODS: The REFINE-Reykjavik study is prospective and population-based with CAC-scoring and carotid plaque ultrasound assessment, both presence and area. A total of 948 individuals without clinical CHD were included in the study. CAC scores were categorized into 0,1-100,101-300 and > 300, and carotid plaque into none, minimal and significant. Three models were applied adjusted for age, sex, and each of the Framingham risk score (FRS), local CHD risk score and established CHD risk factors. RESULTS: Combined carotid plaque- and CAC-presence was highly prevalent, 69.5% for males and 41.7% for females (54.5% overall). TPA outperformed base models in CHD prediction, resulting in statistically significant area under the receiver operator characteristic curve (AUC) increase ranging from 0.02 to 0.05. Most CHD-events in females occurred in individuals classified as low-risk with respect to traditional risk factors but with a gradient in observed risk across carotid plaque categories. CONCLUSIONS: Carotid plaque was strongly associated with the presence and extent of CAC in asymptomatic individuals in a population-based cohort. Carotid plaque predicts incident CHD events over risk scores and may be useful for refined risk prediction in females.

[Prevalence and incidence of type 2 diabetes in Iceland 2005-2018].

INTRODUCTION: The number of people with type 2 diabetes has increased in Iceland in the last few decades. We utilized the national database on prescribed medication from the Directorate of Health to estimate the prevalence and incidence of type 2 diabetes in Iceland and made prediction on the prevalence of type 2 diabetes in Iceland in 10 and 20 years. MATERIAL AND METHODS: Prevalence and incidence of type 2 diabetes for the period 2005-2018 was estimated based on prescriptions of diabetes medication in the national prescription database containing all prescriptions in Iceland during the period. The result was compared to the result from the REFINE-Reykjavik study (prospective, population-based cohort study) from 2004 to 2011 and published data from the USA from 1980 to 2016. RESULTS: The prevalence of type 2 diabetes more than doubled in near all age groups in both men and women in the period 2005-2018. The incidence increased by 2.8% annually (in 18-79 years old). The number of people in Iceland with type 2 diabetes was 10600 in 2018 and had increased from 4200 in the year 2005. Comparison with the results of the REFINE-Reykjavik study showed an underestimation (29% in men and women) of the prevalence of type 2 diabetes. If the increase in type 2 diabetes continues at a similar rate as in the years 2005-2018 the number of people with diabetes in Iceland could be near 24000 in the year 2040. CONCLUSION: Linear increase was seen in incidence and prevalence of people with type 2 diabetes in the years 2005-2018. Similar evolution was seen in USA from 1984. In order to counteract the increase of type 2 diabetes following the same path as has been seen in the USA, targeted measures are needed.

Molecular screening of familial hypercholesterolemia in Icelanders.

Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present study, we carried out a comprehensive screening, using a next-generation sequencing (NGS) panel, for FH culprit mutations in two Icelandic studies representative of either FH families or the general population. We confirmed all previously known mutations in the FH families, and identified two subjects that had been misdiagnosed clinically at young age. We identified six new mutations in the Icelandic FH families and detected three pathogenic mutations in the general population-based study. The application of the NGS panel revealed substantial diagnostic yields in identifying pathogenic mutations, or 68.2% of those with definite clinical diagnosis of FH in the family material and 5.6-fold enrichment in the population-based genetic testing.

Population distribution of traditional and the emerging cardiovascular risk factors carotid plaque and IMT: the REFINE-Reykjavik study with comparison with the Tromsø study.

OBJECTIVES: Population statistics for carotid plaque and cardiovascular risk factors reported in scientific journals are usually presented as averages for the population or age and sex adjusted, rather than sex and age groups. Important population differences about atherosclerosis and cardiovascular risk factors may thus be missed. We compare the distribution of cardiovascular risk factors, carotids plaque and carotid intima-media thickness (CIMT) in two population-based studies. METHODS: Carotid artery atherosclerotic plaque prevalence and risk factors levels for cardiovascular disease by sex in 5-year age groups from the Risk Evaluation For Infarct Estimates Reykjavik study (REFINE-Reykjavik study) were compared with data from the Tromsø 6 study. RESULTS: The threshold of carotid plaque presence in the Tromsø 6 study fell between minimal and moderate plaque defined in the REFINE-Reykjavik study reflecting carotid plaque prevalence. The prevalence of minimal carotid plaque in the REFINE-Reykjavik study was 47% in men (40-69 years old) and 38% in women and 11% in men and 7% in women of moderate plaque. The prevalence of any plaque in the Tromsø 6 study was 35% in men and 27% in women. The mean (CIMT) was similar in the studies. In the Tromsø 6 study mean systolic blood pressure was 8 mm Hg higher in men and 10 mm Hg higher in women, mean low-density lipoprotein was 0.5 mmol/L higher in men and 0.3 mmol/L higher in women and the prevalence of smoking was 4% higher in men and 9% higher in women. However, body mass index was 0.8 kg/m2 higher in men and 0.9 kg/m2 in women in the REFINE-Reykjavik study. CONCLUSION: Comparison between Iceland and Norway revealed differences in the prevalence of carotid plaque, which was assumed to be due to different definition of plaque. However, clinically significant differences in conventional cardiovascular risk factors were seen. This underscores the importance of detailed comparison of population data across different populations.

Predictors of carotid plaque progression over a 4-year follow-up in the Reykjavik REFINE-study.

BACKGROUND AND AIMS: Carotid plaque is an arterial marker suggested as a surrogate end point for cardiovascular disease. The aim of this study was to examine the association of risk factors at visit 1 with plaque formation and progression of total plaque area (TPA) during follow-up. METHODS: We examined 1894 participants (50-69 years of age) in the population-based REFINE (Risk Evaluation For INfarct Estimates)-Reykjavik study. RESULTS: Among those with no plaque at baseline, plaque formation was associated with low density lipoprotein, sex, waist, former smoker and physical activity. Furthermore, both the Icelandic Heart Association (IHA) coronary heart disease (CHD) risk score and the atherosclerotic cardiovascular disease (ASCVD) risk score were highly associated with plaque formation in these individuals (p < 0.001) and a better cardiovascular health score was protective. In those with plaque present at baseline, metabolic syndrome was associated with increased risk, while older age and statin use were associated with reduced risk of new plaque formation. Statin use was the only factor associated with the relative TPA progression, where participants not on treatment had 5.7% (p=0.029) greater rate of progression compared with statin users. CONCLUSIONS: A number of conventional risk factors at visit 1 were individually associated with plaque formation, also when combined into CHD and ASCVD risk scores, but not with the relative progression in TPA. Medical intervention with statins can reduce the relative progression rate of TPA in the general population with low grade of atherosclerosis, supporting statin use to slow progression of atherosclerosis.

Prevalence and determinants of carotid plaque in the cross-sectional REFINE-Reykjavik study.

OBJECTIVE: Carotid plaque and intima-media thickness are non-invasive arterial markers that are used as surrogate end points for cardiovascular disease. The aim was to assess the prevalence and severity of carotid plaque, and examine its determinant risk factors and their association to the common carotid artery intima-media thickness (CCA-IMT) in a general population. METHODS: We examined 6524 participants aged 25-69 years in the population-based REFINE (Risk Evaluation For INfarct Estimates)-Reykjavik study. Plaques at the bifurcation and internal carotid arteries were evaluated. Mean CCA-IMT was measured in the near and far walls of the common carotid arteries. RESULTS: The prevalence of minimal, moderate and severe plaque was 35.0%, 8.9% and 1.1%, respectively, and the mean CCA-IMT was 0.73 (SD 0.14) mm. Age, sex, smoking and type 2 diabetes mellitus (T2DM) were the strongest risk factors associated with plaque, followed by systolic blood pressure, total cholesterol, body mass index and family history of myocardial infarct. Low educational level was also strongly and independently associated with plaque. CCA-IMT shared the same risk factors except for a non-significant association with T2DM and family history of myocardial infarction (MI). Participants with T2DM had greater plaque prevalence, 2-fold higher in those <50 years and 17-30% greater in age groups 50-54 to 60-64, and more significant plaques (moderate or severe) were the difference in prevalence was 24% in age group 50-54 and ≥60% in older age groups, compared with non-T2DM. CONCLUSIONS: Carotid plaque and CCA-IMT have mostly common determinants. However, T2DM and family history of MI were associated with plaque but not with CCA-IMT. Greater prevalence and more severe plaques in individuals with T2DM raise the concern that with increasing prevalence of T2DM we may expect an increase in atherosclerosis and its consequences.

Similar decline in mortality rate of older persons with and without type 2 diabetes between 1993 and 2004 the Icelandic population-based Reykjavik and AGES-Reykjavik cohort studies.

BACKGROUND: A decline in mortality rates due to cardiovascular diseases and all-cause mortality has led to increased life expectancy in the Western world in recent decades. At the same time, the prevalence of type 2 diabetes, a disease associated with a twofold excess risk of cardiovascular disease and mortality, has been increasing. The objective of this study was to estimate the secular trend of cardiovascular and all-cause mortality rates in two population-based cohorts of older persons, with and without type 2 diabetes, examined 11 years apart. METHODS: 1506 participants (42% men) from the population-based Reykjavik Study, examined during 1991-1996 (median 1993), mean age 75.0 years, and 4814 participants (43% men) from the AGES-Reykjavik Study, examined during 2002-2006 (median 2004), mean age 77.2 years, age range in both cohorts 70-87 years. The main outcome measures were age-specific mortality rates due to cardiovascular disease and all causes, over two consecutive 5.7- and 5.3-year follow-up periods. RESULTS: A 32% decline in cardiovascular mortality rate and a 19% decline in all-cause mortality rate were observed between 1993 and 2004. The decline was greater in those with type 2 diabetes, as illustrated by the decline in the adjusted hazard ratio of cardiovascular mortality in individuals with diabetes compared to those without diabetes, from 1.88 (95% CI 1.24-2.85) in 1993 to 1.46 (95% CI 1.11-1.91) in 2004. We also observed a concurrent decrease in major cardiovascular risk factors in both those with and without diabetes. A higher proportion of persons with diabetes received glucose-lowering, hypertensive and lipid-lowering medication in 2004. CONCLUSIONS: A decline in cardiovascular and all-cause mortality rates was observed in older persons during the period 1993-2004, in both those with and without type 2 diabetes. This decline may be partly explained by improvements in cardiovascular risk factors and medical treatment over the period studied. However, type 2 diabetes still persists as an independent risk factor for cardiovascular mortality.

Association of type D personality with unhealthy lifestyle, and estimated risk of coronary events in the general Icelandic population.

BACKGROUND: Type D personality is associated with an increased morbidity and mortality risk in cardiovascular disease patients, but the mechanisms explaining this risk are unclear. We examined whether Type D was associated with coronary artery disease (CAD) risk factors, estimated risk of developing CAD, and previous cardiac events. DESIGN: Cross-sectional study in the general Icelandic population. METHODS: A random sample of 4753 individuals (mean age 49.1 ± 12.0 years; 49% men) from the REFINE-Reykjavik study completed assessments for Type D personality and conventional CAD risk factors. Ten-year risk of developing CAD was estimated with the Icelandic risk calculator. RESULTS: Type D personality (22% of sample) was associated with a higher prevalence of hypertension (35 vs. 31%, p = 0.009), but less use of hypertension medication (58 vs. 65%, p = 0.013) in hypertensives, more diabetes (6 vs. 4%, p = 0.023), wider waist circumference (p = 0.007), and elevated body mass index (p = 0.025) and blood lipids (p < 0.05). Type D individuals reported less physical exercise (p = 0.000) and more current (26 vs. 21%, p = 0.003) and former smoking (48 vs. 44%, p = 0.036). Estimates of 10-year risk of CAD were higher in Type D individuals (12.4%, 95% CI 1.9 to 23.8%), and Type Ds reported more previous cardiac events than non-Type Ds (5 vs. 3%, p < 0.01; OR 1.71, 95% CI 1.21 to 2.42). CONCLUSIONS: In the general Icelandic population, Type D personality was associated with differences in lifestyle-related CAD risk factors, a higher estimated risk of developing CAD, and higher incidence of previous cardiac events. Unhealthy lifestyles may partly explain the adverse cardiovascular effect of Type D personality.

[Early life residency associated with the risk of developing type 2 diabetes - the population-based Reykjavík study]. / Tengsl busetu fyrstu 20 aeviarin vid ahaettu a sykursyki af tegund 2.

INTRODUCTION: Sedentary lifestyle and energy rich food have been associated with the risk of developing type 2 diabetes; limited data are available on environmental conditions in childhood on this risk later in life. The objective was to study if residency in the first 20 years of life affected the risk of developing type 2 diabetes. METHODS: In a cohort of 17811 men (48%) and women, mean age 53 years (range 33-81) participating in the population-based Reykjavík Study from 1967-91, 29% grew up in rural and 35% in coastal areas for an average of 20 years before moving to urban Reykjavík, but 36% lived in Reykjavík from birth. The prevalence of type 2 diabetes according to residency in early life was examined. RESULTS: The relative risk of developing type 2 diabetes was 43% lower in men (RR 0.57; 95% CI 0.43-0.77) and 26% lower (RR 0.74; 95% CI 0.56-0.99) in women living in rural areas for the first 20 years of their life compared with those living in urban Reykjavík from birth. The low prevalence among those that grew up in rural areas was maintained through the age categories of 55-64 years and 65 years and older. CONCLUSIONS: Our findings indicate that persons growing up in rural areas in early 20th century Iceland had lower risk of developing type 2 diabetes later in life when compared with peers living in Reykjavík from birth. We postulate a prolonged effect of early development on glucose metabolism and risk of developing type 2 diabetes.

Serum levels of marine-derived n-3 fatty acids in Icelanders, Japanese, Koreans, and Americans--a descriptive epidemiologic study.

In the 1990s Iceland and Japan were known as countries with high fish consumption whereas coronary heart disease (CHD) mortality in Iceland was high and that in Japan was low among developed countries. We described recent data fish consumption and CHD mortality from publicly available data. We also measured CHD risk factors and serum levels of marine-derived n-3 and other fatty acids from population-based samples of 1324 men in Iceland, Japan, South Korea, and the US. CHD mortality in men in Iceland was almost 3 times as high as that in Japan and South Korea. Generally, a profile of CHD risk factors in Icelanders compared to Japanese was more favorable. Serum marine-derived n-3 fatty acids in Iceland were significantly lower than in Japan and South Korea but significantly higher than in the US.

Effects of statin medication on mortality risk associated with type 2 diabetes in older persons: the population-based AGES-Reykjavik Study.

OBJECTIVE: To examine if the beneficial effect of statin medication on mortality seen in randomised clinical trials of type 2 diabetes applies equally to observational studies in the general population of older people. DESIGN: A prospective, population-based cohort study. SETTING: Reykjavik, Iceland. PARTICIPANTS: 5152 men and women from the Age, Gene/Environment Susceptibility-Reykjavik Study, mean age 77 years, range of 66-96 years. MAIN OUTCOME MEASURE: Cardiovascular and all-cause mortalities and the RR of dying according to statin use and history of coronary heart disease (CHD) in persons with type 2 diabetes and those without diabetes with a median follow-up time of 5.3 years, until end of 2009. RESULTS: The prevalence of type 2 diabetes was 12.4% of which 35% used statins. Statin use was associated with a 50% (95% CI 8% to 72%) lower cardiovascular mortality and 53% (29% to 68%) lower all-cause mortalities in persons with diabetes. For those without diabetes, statin use was associated with a 16% (-24% to 43%) lower cardiovascular and 30% (11% to 46%) lower all-cause mortalities. Persons with diabetes using statins had a comparable risk of cardiovascular and all-cause mortality to that of the general population without diabetes. The effect was independent of the level of glycaemic control. CONCLUSION: This observational study lends important support to existing data from randomised clinical trials. These data suggest that in the general population of older people with diabetes, statin medication markedly reduces the excess cardiovascular and all-cause mortality risk, irrespective of the presence or absence of coronary heart disease or glucose-lowering medication.

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque.

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.

Analysing the large decline in coronary heart disease mortality in the Icelandic population aged 25-74 between the years 1981 and 2006.

BACKGROUND: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s. We examined how much of the decrease between 1981 and 2006 could be attributed to medical and surgical treatments and how much to changes in cardiovascular risk factors. METHODOLOGY: The previously validated IMPACT CHD mortality model was applied to the Icelandic population. The data sources were official statistics, national quality registers, published trials and meta-analyses, clinical audits and a series of national population surveys. PRINCIPAL FINDINGS: Between 1981 and 2006, CHD mortality rates in Iceland decreased by 80% in men and women aged 25 to 74 years, which resulted in 295 fewer deaths in 2006 than if the 1981 rates had persisted. Incidence of myocardial infarction (MI) decreased by 66% and resulted in some 500 fewer incident MI cases per year, which is a major determinant of possible deaths from MI. Based on the IMPACT model approximately 73% (lower and upper bound estimates: 54%-93%) of the mortality decrease was attributable to risk factor reductions: cholesterol 32%; smoking 22%; systolic blood pressure 22%, and physical inactivity 5% with adverse trends for diabetes (-5%), and obesity (-4%). Approximately 25% (lower and upper bound estimates: 8%-40%) of the mortality decrease was attributable to treatments in individuals: secondary prevention 8%; heart failure treatments 6%; acute coronary syndrome treatments 5%; revascularisation 3%; hypertension treatments 2%, and statins 0.5%. CONCLUSIONS: Almost three quarters of the large CHD mortality decrease in Iceland between 1981 and 2006 was attributable to reductions in major cardiovascular risk factors in the population. These findings emphasize the value of a comprehensive prevention strategy that promotes tobacco control and a healthier diet to reduce incidence of MI and highlights the potential importance of effective, evidence based medical treatments.

[Trends in body weight and diabetes in forty years in Iceland]. / Thróun holdafars og sykursýki í 40 ár á Islandi.

OBJECTIVE: Obesity and diabetes are increasing problems worldwide. Therefore, new data on these issues are of importance. Here, we publish data on body mass index (BMI) and prevalence of diabetes of type 2 in Iceland. MATERIAL AND METHODS: Mean BMI (kg/m2), prevalence of diabetes type 2 and obesity in people aged 45-64 years were evaluated from 1967 to 2007. Data on type 2 diabetes was based on four population Icelandic Heart Association studies (newest the REFINE (The Risk Evaluation For INfarct Estimates) Reykjavik study from 2006) with total of 17.757 individuals. Data on BMI was in addition based on three further studies, total 20.519 individuals. The same estimates were then performed for 25-84 year old people in the years 2004-2007. These were based on data from the REFINE Reykjavik study 2.410 individuals and the AGES Reykjavik study 3.027 individuals and. RESULTS: In the years 1967-2007 mean BMI increased by 2 units in both genders (45-64 year) and the prevalence of type 2 diabetes doubled in men, while the increase in women was 50%. In the years 2004-2007 the prevalence of diabetes type 2 in 25-84 year old people was 6% in men and 3% in women and the prevalence of obesity was 23% in men and 21% in women. CONCLUSIONS: Mean BMI is increasing in Iceland, especially after 1980. Prevalence of diabetes coincides with increasing body mass index.

Unfavourable risk factors for type 2 diabetes mellitus are already apparent more than a decade before onset in a population-based study of older persons: from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik).

We evaluated midlife risk factors of developing type 2 diabetes mellitus (T2DM) in late life in a population-based study of older persons. A cohort of 2,251 persons, aged 65-96, participated in AGES-Reykjavik in 2002-2004; all attended the Reykjavik Study 26 years earlier, at the mean age of 50. Based on glucometabolic status in 2002-2004 the participants are divided into a normoglycemic control group (n = 1,695), an impaired fasting glucose (IFG) group (n = 313) and T2DM group (n = 243). Change in risk parameters from midlife is evaluated retrospectively in these three groups. Since examined earlier 14.3% of men and 8.2% of women developed T2DM. A family history of diabetes was reported in 39.5% of T2DM compared to 19.3% in both IFG and normoglycemics. The T2DM and IFG groups currently have higher levels of fasting triglycerides, greater body mass index (BMI) and higher systolic blood pressure than normoglycemics and this difference was already apparent in midlife. In late life, two or more metabolic syndrome criteria are present in 60% of the T2DM groups compared to 25% in normoglycemic groups. T2DM with impaired cardiovascular health is more marked in women than men when compared with normoglycemics. Family history and higher levels of BMI, triglycerides and systolic blood pressure in midlife are associated with the development of T2DM in late life, suggesting risk can be evaluated long before onset. A continued rise in risk factors throughout life allows for more aggressive measures in preventing or delaying development of T2DM and its effect on cardiovascular health.

Systematic family screening for familial hypercholesterolemia in Iceland.

OBJECTIVE: This study compares a novel approach using systematic family screening for patients in Iceland who have familial hypercholesterolemia (FH) with conventional proband screening and assesses the sensitivity and specificity of diagnosing FH by cholesterol measurements compared with mutational testing of family members. METHODS AND RESULTS: Probands with the I4T+2C mutation were traced to common ancestors. A downtracing of each family lineage was performed back to the oldest living offspring (key individuals); these individuals were recruited for cholesterol measurement and mutation testing. The sensitivity and specificity of cholesterol measurements was assessed against mutational analysis. Eleven probands clustered into 4 families. There were 364 key individuals identified among their descendants. Eighty-four percent responded, and 11% were positive for the mutation. There were 78 offspring of the positive key individuals, and 40 of those were carriers. Compared with use of the conventional first-degree relative approach, an additional 19% of FH individuals, including key individuals and their descendants, were identified. As diagnostic criteria, cholesterol measurements in the families had 95% specificity and 94% sensitivity. CONCLUSIONS: Tracing FH probands to common ancestors and screening the oldest offspring in each family lineage adds considerably to the conventional method of FH screening (testing first-degree relatives). This may have relevance in other founder populations.