Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects

BackgroundDespite the greater prevalence of familial hypercholesterolemia (FH) in subjects with ischemic heart disease (IHD), premature IHD, and severe hypercholesterolemia (low-density lipoprotein ≥190 mg/dl), overall prevalence estimates are not available.ObjectivesThe aim of this study was to provide worldwide estimates of FH prevalence in subjects with IHD, premature IHD, and severe hypercholesterolemia compared with those in the general population.MethodsIn this systematic review and meta-analyses, Embase, PubMed, and the Web of Science were searched until June 3, 2019, for peer-reviewed papers and conference abstracts reporting heterozygous FH prevalence in nonfounder populations, revealing 104 studies eligible for inclusion.ResultsEstimates of FH prevalence were pooled using random-effects meta-analyses and were 0.32% (95% confidence interval [CI]: 0.26% to 0.39% [corresponding to 1:313]) among 10,921,310 unique subjects in the general population (33,036 patients with FH) on the basis of 44 studies, 3.2% (95% CI: 2.2% to 4.3% [1:31]) among 84,479 unique subjects with IHD (2,103 patients with FH) on the basis of 28 studies, 6.7% (95% CI: 4.9% to 8.7% [1:15]) among 31,316 unique subjects with premature IHD (1,471 patients with FH) on the basis of 32 studies, and 7.2% (95% CI: 4.6% to 10.8% [1:14]) among 17,728 unique subjects with severe hypercholesterolemia (920 patients with FH) on the basis of 7 studies. FH prevalence in the general population was similar using genetic versus clinical diagnoses. Seventeen of 195 countries (9%) in the world have reported FH prevalence for the general population, leaving 178 (91%) countries in the world with unknown prevalence.ConclusionsCompared with 1:313 among subjects in the general population, FH prevalence is 10-fold higher among those with IHD, 20-fold higher among those with premature IHD, and 23-fold higher among those with severe hypercholesterolemia. The prevalence of FH is unknown in 90% of countries in the world.     

Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: results from a Swedish population based study 1964-95

OBJECTIVE: Although short term prognosis has improved in patients with systemic lupus erythematosus (SLE) during the early disease course, less is known about the longterm prognosis. METHODS: A cohort of 4737 patients with a diagnostic code of SLE was identified 1964-94 in the Swedish Hospital Discharge Register and followed by linkage to the Cause of Death Register until the end of 1995. Mortality was separately analyzed in 3 different calendar periods (1964-75, 1975-84, 1985-95). The relative risk of death was estimated as standardized mortality ratio (SMR) using the Swedish population as a reference. RESULTS: In total 2314 patients were deceased. Mortality was 3-fold increased (SMR = 3.63, 95% CI 3.49, 3.78) and cardiovascular disease (CVD) was the major cause of death. Patients aged 20-39 years at the first discharge had a 16-fold increased risk of death from coronary heart disease (SMR = 15.99, 95% CI 10.4, 23.6). All-cause mortality had decreased since 1975 and the reason for this decrease was entirely due to a decrease in causes attributed to SLE, but not CVD. Patients aged 20-39 years at the first discharge had a pronounced decrease in mortality, with SMR 33.59 (95% CI 24.3, 45.3) before 1975 compared with SMR 14.23 (95% CI 8.70, 22.0) after 1984. CONCLUSION: Cardiovascular disease was the major cause of death in patients with SLE and young patients had a pronounced increased risk of death. Even if all-cause mortality had declined during the last 2 decades due to causes attributed to SLE, the risk of cardiovascular death remained unchanged.     

The relationship between a low treated blood pressure and IHD mortality: a report from the DHSS Hypertension Care Computing Project (DHCCP)

The suggestion that treating blood pressure to below a certain level may increase IHD mortality is controversial. We investigated the influence of treated blood pressure on mortality in the DHSS Hypertension Care Computer Project. Mortality was examined by quintiles of treated diastolic blood pressure (DBP) in 2,145 patients treated for a minimum period of one year and subsequently followed for an average of four years. One hundred and seventy five patients died; 71 from IHD. In men and women all cause mortality increased with level of treated DBP. In men IHD mortality showed a U-shaped distribution with an age-adjusted rate of 15.2 per 1,000 person years in the lowest fifth (DBP less than 86 mmHg) comparable to that of 15.6 per 1,000 in the upper (DBP greater than or equal to 103 mmHg). A similar pattern could not be established in women due to very few IHD deaths. IHD mortality was further examined separately for men by prior history of IHD. An increase in IHD deaths in the lowest fifth of treated blood pressure was found for men both with and without a history of IHD. No similar pattern of IHD mortality was obtained for untreated DBP or treated systolic pressure. However, we cannot exclude the possibility that the risk of low treated DBP is secondary to ischaemic heart disease.     

Ischemic heart disease in patients from Northwest Spain with biopsy proven giant cell arteritis. A population based study

OBJECTIVE: To assess the incidence, mortality, and predictors of ischemic heart disease (IHD) in patients from the Lugo region of Northwest Spain with biopsy-proven giant cell arteritis (GCA). METHODS: Retrospective study of patients with biopsy-proven GCA diagnosed from 1981 to 2001 at the single hospital for a population of 250,000 people. A survival analysis was performed. Hazard ratios and standardized mortality ratio (SMR) as well as predictors of IHD in patients with biopsy-proven GCA were also assessed. RESULTS: Nineteen (9%) of the 210 patients with biopsy-proven GCA diagnosed during the period of study had IHD. The incidence of IHD in patients with GCA was 12.6/1000 person-years at risk (95% CI 6.9-21.0). During the study period 1981-2000 the population aged > or = 50 years in Lugo was roughly 100,000, and the mortality rate due to IHD in patients with GCA for that population was 8/100,000. The SMR in patients with GCA due to IHD was 1.62 (95% CI 0.70-3.20). Mortality in patients with GCA who had IHD was higher than in those patients without IHD (age and sex adjusted hazard ratio 2.81, 95% CI 1.51-5.21; p = 0.001). Age (hazard ratio 1.15), hypertension (hazard ratio 2.51), and abnormal temporal artery on physical examination (hazard ratio 0.36) at the time of diagnosis of GCA were the best predictors of IHD over the followup period in patients with biopsy-proven GCA. CONCLUSION: Our observations suggest that mortality due to IHD in patients from Lugo with GCA is not much higher than that reported in the Spanish population aged 50 years and older. However, mortality in patients with GCA with IHD is higher than in GCA patients without IHD.     

Triglyceride,albuminuria and blood pressure are the major associations of non-fatal cardiovascular disease in Chinese type 2 diabetes

Diabetes is associated with an increased risk of cardiovascular disease (CVD). We studied risk factors for CVD in a cohort of Chinese type 2 diabetic patients recruited between July 1994 and August 1998. Ischemic heart disease (IHD) was defined as a history of: (i) confirmed coronary artery disease (with typical electrocardiographic changes or a positive exercise tolerance test) in patients under care of a cardiologist; (ii) documented myocardial infarction; or (iii) coronary interventions such as angioplasty or coronary artery bypass graft. Cerebrovascular accident (CVA) was defined as any definite cerebral vascular event with or without residual neurological deficit. CVD was defined as a history of IHD or CVA. The study enrolled 3333 patients, including 1370 men (41.1%) and 1963 women (58.9%) of mean age 55.9±13.3 years (range, 16–91 years; median, 57 years). A total of 279 patients (8.4%) had CVD (including 4.1% with CVA, 4.9% with IHD, and 0.6% with both CVA and IHD). Men had an overall higher rate of CVD than women (10.1% vs. 7.1%, p=0.002). All cardiovascular diseases showed a progressive increase in prevalence with increasing age with the peak among those aged ≤60 years. Logistic regression analysis was used to examine the predictive value of age, body mass index, waist-to-hip ratio, blood pressure, fasting plasma glucose, glycated hemoglobin, lipid profiles, albuminuria, smoking and family history of diabetes on the risk of CVD. In women, age, systolic blood pressure and triglyceride level and in men, age and albuminuria, were predictive for CVD. In conclusion, 8.4% of Hong Kong Chinese type 2 diabetic patients being followed in a hospital out-patient setting have a history of established and confirmed cardiovascular disease. Age, systolic blood pressure, triglyceride and albuminuria were the major independent risk factors for non-fatal cardiovascular diseases. Received: 30 January 2002 / Accepted in revised form: 15 October 2002 Correspondence to G.T.C Ko     

Diabetes mellitus and risk of fatal ischaemic heart disease by gender: 18 years follow-up of 74,914 individuals in the HUNT 1 Study.

AIM: To study long-term mortality from ischaemic heart disease (IHD) in subjects with and without diabetes and how the association between diabetes and fatal IHD is influenced by gender and established cardiovascular disease (CVD). METHODS AND RESULTS: In 1984-86, all inhabitants aged 20 years or older in Nord-Tr?ndelag County, Norway were invited to the HUNT Study. A total of 74,914 participated in our study, 2100 of them with prevalent diabetes. During 18 years of follow-up, 19,967 persons died. Among people without diabetes or CVD at baseline, men had twice (HR 2.20, CI 2.00-2.41) the rate of fatal IHD compared with women. With diabetes present, the gender gap was substantially reduced (HR 1.25, CI 0.9-1.72), and if both diabetes and CVD were present, IHD mortality in men and women was identical (HR 1.1, CI 0.79-1.64). Gender specific analyses showed a stronger association of diabetes with IHD mortality in women (HR 2.71, CI 2.33-3.16) compared with men (HR 1.98, CI 1.70-2.30, test for interaction, P < 0.01). CONCLUSION: Diabetes is a stronger predictor for IHD mortality in women than in men, and diabetes attenuates the usual gender gap in IHD mortality. With both diabetes and established CVD present, the gender gap is fully attenuated.     

The Lewis blood group--a new genetic marker of ischaemic heart disease.

In a cohort of 3383 men aged 53 to 74 in the Copenhagen Male Study we investigated the association between ischaemic heart disease (IHD) and the Lewis blood group, assigned to chromosome 19. Among men with the Le(a-b-) phenotype, 8% had a history of non-fatal myocardial infarction, among others the frequency was 4%. The corresponding odds ratio was (95% confidence interval: CI) 1.9 (1.2-3.0) P < 0.01, men with Le(a-b-) had a risk-factor profile and pattern of disease resembling that of Reaven's syndrome X. In a subsequent prospective study 343 men with arteriosclerotic stigmas were excluded. The men had their morbidity and mortality recorded over the next 4 years. One-hundred-and-one men suffered IHD; 26 dying from IHD. In total 162 men died. Men with Le(a-b-) had an increased risk of death from IHD compared with others. Adjusted for age, relative risk (RR) (95% CI) was: 4.4 (1.9-10.3), P < 0.001, and for all causes of mortality: RR = 1.6 (1.0-2.6), P < 0.05. Men with the Le(a-b-) phenotype had an increased risk of an IHD event compared to men with other phenotypes (RR = 1.6 (0.9-2.8), P = 0.10) and a significantly higher IHD case fatality rate (RR = 2.8 (1.5-5.2), P = 0.01). The finding that the Le(a-b-) phenotype is a genetic marker of IHD risk may have implications in terms of prevention. The Le(a-b-) phenotype may also contribute to providing an explanation for the substantial ethnic differences found in the incidence of IHD. The similar risk-factor profile and pattern of disease found between Le(a-b-) men and individuals with Reaven's syndrome X is hypothesized to be due to a close genetic relationship on chromosome 19.     

Mutations in the lipoprotein lipase gene associated with ischemic heart disease in men. The Copenhagen city heart study.

The aim of this study was to test the hypothesis that the Asp9Asn substitution and the T(-93)-->G mutation in the promoter of the lipoprotein lipase gene affect plasma lipid levels and thereby the risk of ischemic heart disease (IHD). We genotyped 9033 men and women from a general population sample and 940 patients with IHD. The frequency of both the G allele and the Asn9 allele in the general population sample was approximately 0.015 for both men and women. These 2 mutations appeared together in 95% of carriers. The average triglyceride-raising effect associated with double heterozygosity for the T(-93)-->G mutation and the Asp9Asn substitution was 0.28 mmol/L (P=0.004) and 0.16 mmol/L (P=0.10) in men and women, respectively. On logistic regression analysis allowing for age, the risk of IHD for double heterozygous men and women was increased 90% (95% confidence interval [CI], 20% to 200%) and 30% (95% CI, -40% to 170%), respectively, compared with noncarriers. When, in addition, other conventional cardiovascular risk factors were allowed for, the risk of IHD for double heterozygous men and women was increased 70% (95% CI, 0% to 190%) and 20% (95% CI, -50% to 180%), respectively. Of the overall risk of IHD in men in the general population, the fraction attributable to double heterozygosity was 3%, similar to the 5% attributable to diabetes mellitus. These results demonstrate that the Asp9Asn substitution is in linkage disequilibrium with the T(-93)-->G mutation and that the double-heterozygous carrier status is associated with elevated plasma triglycerides and an increased risk of IHD in men.     

The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients

OBJECTIVE: To determine the contribution of classical risk factors to the development of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolaemia (FH). DESIGN: A retrospective, multi-centre, cohort study. Extensive data were collected by scrutinizing medical records and the use of questionnaires. Multivariate Cox regression was used to study the relationship between potential risk factors and the occurrence of CVD. SETTING AND SUBJECTS: We included 2400 FH patients from 27 Dutch lipid clinics. The diagnosis of FH was based upon the presence of a low-density lipoprotein receptor mutation or upon strict clinical criteria. MAIN OUTCOME MEASURES: Cardiovascular mortality and CVD. RESULTS: During 112.943 person-years, 782 (32.6%) patients had had at least one cardiovascular event. Male gender (RR 2.82, 95% CI 2.37-3.36), smoking (RR 1.67, 95% CI 1.40-1.99), hypertension (RR 1.36, 95% CI 1.06-1.75), diabetes mellitus (RR 2.19, 95% CI 1.36-3.54), low HDL-C (RR 1.37, 95% CI 1.15-1.63) and elevated lipoprotein(a) levels (RR 1.50, 95% CI 1.20-1.79) proved to be independent CVD risk factors. These six risk factors explained 18.7% of the variation in the occurrence of CVD. CONCLUSIONS: Male gender, smoking, hypertension, diabetes mellitus, HDL cholesterol and lipoprotein(a) levels proved to be important risk factors for CVD in FH patients. In addition to the routine institution of statin therapy, controlling these factors needs special attention in the management of this disorder.     

Impact of parental history on patients' cardiovascular mortality in rheumatoid arthritis

BACKGROUND: Patients with rheumatoid arthritis are at increased risk of death from cardiovascular disease (CVD). This risk is influenced by the inflammatory activity of the rheumatoid arthritis as well as by traditional risk factors for CVD. However, little is known about whether or to what extent hereditary factors for CVD contribute additional risk in patients with rheumatoid arthritis. OBJECTIVE: To assess the clinical impact of a parental history of CVD in patients with rheumatoid arthritis. METHODS: Population based cohort study of 10,805 Swedish patients with rheumatoid arthritis aged 16-67 years during follow up (1990-2000). Parents, and cardiovascular deaths among patients and parents, were identified through register linkages. Relative risk of death v the general population was assessed using standardised mortality ratios (SMR), which were compared by Poisson regression. RESULTS: Rheumatoid patients with a parental history of fatal CVD had an SMR of death from CVD of 2.9 (95% confidence interval, 2.5 to 3.4). By contrast, rheumatoid patients without a parental history of fatal CVD had an SMR of 1.7 (1.2 to 2.3). A parental death from CVD was associated with a 70% increase in the risk of fatal CVD in rheumatoid arthritis (SMR ratio = 1.7 (1.2 to 2.4), and an increase in the 10 year mortality from CVD from 5% to 10% in men and from 2% to 4% in women aged 50 to 67 years. CONCLUSIONS: Parental history of death from CVD is an important (and easily assessable) risk factor for fatal CVD in rheumatoid arthritis.     

Comparison of the risk of fatal coronary heart disease in treated xanthomatous and non-xanthomatous heterozygous familial hypercholesterolaemia: a prospective registry study

BACKGROUND: A clinical diagnosis of familial hypercholesterolaemia (FH) is often made in the absence of tendon xanthomata (TX), which are not usually present before the fourth decade of life. The prognosis of treated non-xanthomatous (TX-) FH is uncertain and the objective of this study was to compare mortality from coronary heart disease (CHD) in patients with treated TX+ (definite) and TX- (possible) heterozygous FH. METHODS: A diagnosis of definite or possible FH was based on raised cholesterol levels (>7.5 mmol/l) and a family history of premature CHD or hypercholesterolaemia. Patients were recruited from 21 outpatient lipid clinics in the UK from 1980 to 1998. The cohort of 1569 patients with TX+ FH were followed for 12754 person years and the cohort of 1302 patients with TX- FH for 10238 person years. The standardised mortality ratio (SMR) was calculated from the ratio of the number of deaths observed to the number expected in the general population of England and Wales (SMR=100 for reference population). FINDINGS AND DISCUSSION: CHD accounted for 64 (63%) of the 102 deaths in the TX+ cohort and 38 (57%) of the 67 deaths in the TX- cohort with the SMR for a fatal coronary event being, respectively, 294 (95% confidence interval 228, 380, P<0.00001) and 205 (95% CI 145, 282, P=0.0001). The similarly elevated CHD mortality risk suggests that, in adulthood, both groups of patients should be treated equally aggressively with HMG Co A reductase inhibitors (statins).     

Comparison of risk factors for fatal stroke and ischemic heart disease: a prospective follow up of the health survey for England

Objectives

The aim was to compare risk factors for stroke and ischemic heart disease (IHD) in a large general population cohort.

Methods

A prospective cohort of 82,380 participants (aged 55.4 [SD 14.2 yrs], 44.8% men) without known history of cardiovascular diseases (CVD) at baseline was pooled from ten years (1994–2004) of the Health Survey for England. Study members were followed, on average, over 8 years for cause-specific mortality using linkage to national registers.

Results

There were 806 and 1346 stroke and IHD deaths, respectively. The major risk factors for stroke included age (hazard ratio [HR] = 1.15, 95% CI, 1.13–1.17), smoking (HR = 1.71; 1.20–2.44), diabetes (HR = 1.75; 1.05–2.93), total cholesterol (HR per SD = 0.78; 0.69–0.89), and systolic BP (HR per SD = 1.22; 1.08–1.38). In addition to these risk factors, IHD was also predicted by high density lipoprotein cholesterol, body mass index, C-reactive protein, and fibrinogen. This pattern of results was consistent among younger (<70 yrs) and older adults.

Conclusion

In a large representative cohort of the general population we found a differential pattern of risk markers for stroke compared with IHD. This was not explained by differences in age at onset of disease.     

Mortality in Barrett's oesophagus: results from a population based study

BACKGROUND: Patients with Barrett's oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett's oesophagus register. METHODS: We constructed a register of all patients diagnosed with columnar mucosa (including specialised intestinal metaplasia) of the oesophagus within Northern Ireland between 1993 and 1999. Deaths occurring within this cohort until 31 December 2000 were identified and mortality rates were compared with the general population. RESULTS: Overall mortality was not raised in Barrett's patients. During 7413 person years of follow up in 2373 patients there were 253 deaths (standardised mortality ratio (SMR) 96 (95% confidence interval (CI) 84-107)). Mortality from oesophageal cancer was raised in patients with specialised intestinal metaplasia (SMR 774 (95% CI 317-1231)) but only 4.7% of patients died from this cancer. Mortality from stroke (SMR 65 (95% CI 37-93)) was significantly lower than the general population while mortality from non-cancerous digestive system diseases was significantly higher (SMR 211 (95% CI 111-311)). Mortality rates from all other causes were similar to those of the general population. CONCLUSIONS: This study demonstrates that the overall mortality rate in patients with Barrett's oesophagus is closely similar to that of the general population. Oesophageal cancer mortality was raised but is an uncommon cause of death in these patients who also appear to have a reduced risk of death from stroke.     

Cardiovascular mortality in hypertensive men according to presence of associated risk factors

To evaluate the risk of cardiovascular disease (CVD) mortality in hypertensive men according to the presence of associated risk factors (ARFs). The population was composed of 29 640 normotensive men without ARFs (reference group) and 60 343 hypertensive men (with and without ARFs) who had a standard health checkup at the Centre d'Investigations Préventives et Cliniques between 1978 and 1988. Mortality data for a mean period of 14 years were analyzed. The following ARFs were considered: total cholesterol >/=2.5 g/L, personal history of diabetes, smoking (current smokers), body mass index >28 kg/m(2), and heart rate >80 bpm. CVD risk related to the presence of isolated hypertension (assessed in hypertensive subjects without ARFs versus the reference group) increased linearly from 15% at the age of 30 years to 134% at the age of 80 years. In hypertensive subjects, one additional ARF increased CVD risk by 56% (47% to 65%, P<0.01) in younger subjects but only by 4% (-8% to 17%, P=NS) in older subjects. The role of hypercholesterolemia and tobacco smoking in CVD mortality was significantly higher in hypertensive subjects aged <55 years than in hypertensive subjects aged >/=55 years (P<0.01), whereas the roles of tachycardia and obesity were not affected by age. In younger hypertensive subjects, evaluation of CVD risk and therapeutic strategies should target ARFS: In older subjects, the presence of high blood pressure levels seems to be the major determinant of CVD risk.     

Temporal Changes in a Novel Metric of Physical Activity Tracking (Personal Activity Intelligence) and Mortality: The HUNT Study,Norway

BackgroundPersonal Activity Intelligence (PAI) is a novel activity metric that translates heart rate variations during exercise into a weekly score. Weekly PAI scores assessed at a single point in time were found to associate with lower risk of premature cardiovascular disease (CVD) mortality in the general healthy population. However, to date, the associations between long-term longitudinal changes in weekly PAI scores and mortality have not been explored.PurposeThe aim of the present study was to prospectively examine the association between change in weekly PAI scores estimated 10 years apart, and risk of mortality from CVD and all-causes.MethodsWe performed a prospective cohort study of 11,870 men and 13,010 women without known CVD in Norway. By using data from the Nord-Trøndelag Health Study (HUNT), PAI was estimated twice, ten years apart (HUNT1 1984-86 and HUNT2 1995-97). Mortality was followed-up until December 31, 2015. Adjusted hazard ratios (AHR) and 95% confidence intervals (CI) for death from CVD and all-causes related to temporal changes in PAI were estimated using Cox regression analyses.ResultsDuring a mean (SD) of 18 (4) years of follow-up, there were 4782 deaths, including 1560 deaths caused by CVD. Multi-adjusted analyses demonstrated that participants achieving a score of ≥100 PAI at both time points had 32% lower risk of CVD mortality (AHR 0.68; CI: 0.54–0.86) for CVD mortality and 20% lower risk of all-cause mortality (AHR 0.80; CI: 71–0.91) compared with participants obtaining <100 weekly PAI at both measurements. For participants having <100 PAI in HUNT1 but ≥100 PAI in HUNT2, the AHRs were 0.87 (CI: 0.74–1.03) for CVD mortality, and 0.86 (CI: 0.79–0.95) for all-cause mortality. We also found an inverse linear relationship between change in PAI and risk of CVD mortality among participants with 0 PAI (P < 0.01), and ≤50 PAI (P = 0.04) in HUNT1, indicating that an increase in PAI over time is associated with lower risk of mortality. Excluding the first three years of follow-up did not substantially alter the findings. Increasing PAI score from <100 PAI in HUNT1 to ≥100 PAI in HUNT2 was associated with 6.6 years gained lifespan.ConclusionAmong men and women without known CVD, an increase in PAI score and sustained high PAI score over a 10-year period was associated with lower risk of mortality.     

Prognosis of patients with a diagnosis of fatty liver--a registry-based cohort study

BACKGROUND/AIMS: There are very limited data available regarding the prognosis of patients with fatty liver. We examined the overall and cause-specific mortality of fatty liver patients in a large Danish cohort. METHODOLOGY: In the Danish National Registry of Patients, we identified 7,372 patients discharged with a diagnosis of fatty liver from a Danish hospital between 1977 and 1993. Causes of death were identified in the Danish Death Registry. We estimated the standardized mortality ratio by comparing with the general population. RESULTS: Most patients (76%) had alcoholic fatty liver. During follow-up, 2,914 (40%) died. The commonest cause of death was hepatobiliary disease (25% of deaths). Mortality was increased 5.4-fold (95% CI 5.2-5.6) in patients with alcoholic fatty liver, and 2.6-fold (95% CI 2.4-2.9) in patients with non-alcoholic or unspecified fatty liver. Overall, in the first year of follow-up, mortality was increased more than 7-fold, almost 5-fold in the second to fifth years, and more than 3-fold after that. Mortality was similar among genders and among diabetics and non-diabetics, and remained increased after censoring patients upon diagnosis of liver cirrhosis. CONCLUSIONS: The mortality of patients with a hospital discharge diagnosis of fatty liver was higher than that of the general population.     

Multiple metabolic risk factors and total and cardiovascular mortality in men with low prevalence of obesity

We investigated the association between the multiple metabolic risk factors and cardiovascular and overall mortality among Korean men, a population with a low prevalence of obesity. This prospective cohort study involved 682,597 Korean men, aged 30-69 years at baseline (1992), who were initially without cancer or debilitating diseases. Death due to ischemic heart disease (IHD), stroke, cardiovascular disease (CVD), and any cause among men relative to metabolic risk factors, including overweight, high blood pressure, high fasting glucose, and high total cholesterol was analyzed. There were 17,785 deaths during the 8.5-year follow-up, of which 874 were due to IHD, 1644 to stroke, and 3306 to CVD. As a function of the number of metabolic risk factors, the relative risk of death from CVD was 2.0 (1.7-2.2), 2.9 (2.5-3.3), 3.5 (3.0-4.1), and 5.0 (3.9-6.4) for 1, 2, 3, and 4 risk factors, respectively, whereas the relative risk of death from all causes was 1.3 (1.2-1.4), 1.5 (1.4-1.6), 1.6 (1.5-1.7), and 1.9 (1.6-2.2) for 1, 2, 3, and 4 risk factors, respectively. The relative risk of IHD, stroke, CVD and all-cause mortality increased linearly with the number of metabolic risk factors. Early identification and strict management of metabolic risk factors should be reinforced in Koreans, even though there is a low prevalence of obesity among this population.     

Decreasing mortality in patients with rheumatoid arthritis: results from a large population based cohort in Sweden, 1964-95

OBJECTIVE: To assess changes in mortality in patients with rheumatoid arthritis (RA) from 1964 to 1995. METHODS: A population based cohort of 46,917 patients with RA was identified from 1964 to 1994, using the Swedish Hospital Discharge Register, and followed until 1995 through linkage to the Cause of Death Register. Mortality was separately analyzed in each inclusion period (1964-75, 1975-84, 1985-94). The relative risk of death was estimated as standardized mortality ratio (SMR) using the Swedish population as a reference RESULTS: All-cause mortality was increased twice the expected (SMR = 2.03, 95% CI 2.00, 2.05). Coronary artery disease was the major cause of death and mortality was increased by 80% (SMR = 1.79, 95% CI 1.75, 1.83). Females with RA aged 20-39 at first discharge had a more than 5-fold increased risk of coronary death (SMR = 5.48, 95% CI 3.45-5.71). From 1975 patients with RA had decreasing all-cause mortality. This decline was most pronounced in patients aged 40-59 at first discharge, where SMR was 2.68 (95% CI 2.45, 2.92) from 1964 to 1974 compared to SMR 1.63 (95% CI 1.37, 1.92) from 1985 to 1994. CONCLUSION: The elevated mortality rates in RA patients compared to the general population have decreased during the last 20 years, possibly due to an increased access to specialized rheumatology care. An excess risk for death in coronary artery disease was, however, present in RA patients, especially patients with early onset of disease.     

Crohn's disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort

BACKGROUND: No previous correlation between phenotype at diagnosis of Crohn's disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. METHODS: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. RESULTS: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30-2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10-3.14)) and males (SMR 1.79 (95% CI 1.11-2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32-3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80-2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. CONCLUSIONS: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.     

Sex differences in the relationships between BMI, WHR and incidence of cardiovascular disease: a population-based cohort study

OBJECTIVE: Body mass index (BMI) is associated with increased incidence of cardiovascular disease (CVD). However, the risk could be very different for individuals with the same body mass. The present study explored whether regional fat distribution, as measured by waist-hip ratio (WHR), could modify the impact of BMI on the risk of CVD in men and women. DESIGN: Prospective population-based study. SUBJECTS: A total of 10 369 men and 16 638 women, 45-73 years old, from general population in Malm?, Sweden.Measurements:All subjects were followed over 7 years for the incidences of first-ever cardiac event (CE) and ischemic stroke in relation to BMI category (<25.0, 25.0-29.9, > or =30.0) and WHR. RESULTS: The prevalence of overweight and obesity was 39.4 and 13.0%, respectively. During follow-up, 1280 subjects suffered a CVD event (750 CE, 530 ischemic stroke). The risk of CVD in women increased with increasing levels of WHR, irrespective of BMI category. In men, WHR (per 1 s.d. increase) was associated with increased incidence of CVD in those with normal weight (relative risk (RR)=1.24; 95% CI: 1.13-1.37) after adjustments for confounding factors. However, WHR was not related to CVD in overweight men (RR=1.06; 95%CI: 0.94-1.20) or obese men (RR=1.04; 95%CI: 0.87-1.24). A significant interaction was observed between sex and WHR on the CVD risk. CONCLUSION: The effect of WHR on incidence of CVD is modified by the overall body weight and by gender. WHR adds prognostic information on the cardiovascular risk in women at all levels of BMI, and in men with normal weight.