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Background: Previous findings regarding physical activity and risk of incident atrial fibrillation (AF) are controversial, focusing on leisure-time physical activity (LTPA) and without distinguishing it from occupational physical activity (OPA). Our aim was to study the association between physical activity and risk of AF, with special attention to the possible divergent effects of OPA and LTPA., Methods and Results: In a prospective, observational cohort study, 17,196 subjects were included from the Copenhagen Population Register. All participants had a physical examination, a 12-lead electrocardiogram (ECG), and answered a questionnaire regarding health and physical activity. Participants without previously diagnosed AF who answered adequately regarding OPA and LTPA were included. LTPA and OPA were each graded into four levels. Follow-up were carried out between 1981-1983, 1991-1994, and 2001-2003. Information regarding hospitalization and mortality was drawn from the National Patient Registry and the Registry of Causes of Death. Outcome was incident AF as determined by follow-up ECG or register diagnosis. In univariable Cox regression analysis all sub-groups of OPA had a significant higher risk of AF compared to moderate OPA. When adjusting for confounders, the risk remained significantly increased for high OPA (hazard ratio (HR) 1.21 (95% confidence interval (CI) 1.02-1.43), p = 0.028), and very high OPA (HR 1.39 (95% CI 1.03-1.88), p = 0.034). We found no significant association between LTPA and incident AF., Conclusions: High and very high OPA were associated with a significantly increased risk of incident AF. LTPA was not associated with risk of incident AF., (© The European Society of Cardiology 2016.)

Background: Social inequality is present in the morbidity as well as the mortality of cardiovascular diseases. This paper aims to quantify and compare the level of educational inequality across different cardiovascular diagnoses., Design: Register based study., Methods: Comparison of the extent of inequality across different cardiovascular diagnoses requires a measure of inequality which is comparable across subgroups with different educational distributions. The slope index of inequality and the relative index of inequality were applied for measuring inequalities in incidence of six cardiovascular diagnoses: ischaemic heart disease, acute myocardial infarction, valvular heart disease, congestive heart failure, atrial fibrillation and stroke in the period 2005-2009. All individuals in the general Danish population aged 35-84 years were followed in national registers regarding hospitalisation, death and education from 1985 to 2009 (annual average of 2.9 million people) to define incident cases., Results: Marked educational inequality was found in the incidence of ischaemic heart disease, acute myocardial infarction, heart failure and stroke (relative index of inequality: 0.37 (95% confidence interval 0.34; 0.40) to 0.60 (0.57; 0.63), absolute index of inequality: -241 (-254.4; -227.4) to -37 (-42.7; -31.1)) while inequality in atrial fibrillation and, in particular, in valvular heart disease was small and insignificant (relative index of inequality: 0.57 (0.49; 0.65) to 0.97 (0.88; 1.08), absolute index of inequality: -29 (-35.1; -21.9) to -1 (-4.8; -3.8))., Conclusion: The degree of educational inequality in cardiovascular diseases depends on the diagnosis, with the highest inequality in ischaemic heart disease, acute myocardial infarction, heart failure and stroke. Small differences were found between men and women., (© The European Society of Cardiology 2015.)

Context and Objective: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear. We tested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population., Design, Setting, and Participants: Adult men (n = 4615) and women (n = 4724) with measurements of endogenous sex hormones during the 1981-1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through potential mediators. Present and previous findings were summarized in meta-analyses., Main Outcome Measures: Plasma total testosterone and total estradiol were measured by competitive immunoassays. Diagnosis of IS was ascertained from the national Danish Patient Registry and the national Danish Causes of Death Registry and verified by experienced neurologists., Results: During follow-up, 524 men and 563 women developed IS. Men with testosterone concentrations ≤10th percentile compared to the 11th-90th percentiles had a hazard ratio for IS of 1.34 (95% confidence interval, 1.05-1.72); 21% of this risk was mediated by body mass index (P = .002) and 14% by hypertension (P = .02). In accordance with this, the corresponding hazard ratio was 1.46 (1.09-1.95) in overweight/obese and hypertensive men. The corresponding hazard ratio in the meta-analysis was 1.43 (1.21-1.70). Other extreme concentrations of testosterone or estradiol were not associated with risk of IS in men or women., Conclusions: Extremely low endogenous testosterone concentrations were associated with high risk of IS in men, a risk mediated in part by body mass index and hypertension. Whether or not low testosterone is a causal factor for IS or merely a biomarker of poor metabolic health is still not known.

Aims: To rank psychosocial and traditional risk factors by importance for coronary heart disease., Methods and Results: The Copenhagen City Heart Study is a prospective cardiovascular population study randomly selected in 1976. The third examination was carried out from 1991 to 1994, and 8882 men and women free of cardiovascular diseases were included in this study. Events were assessed until April 2013. Forward selection, population attributable fraction, and gradient boosting machine were used for determining ranks. The importance of vital exhaustion for risk prediction was investigated by C-statistics and net reclassification improvement. During the follow-up, 1731 non-fatal and fatal coronary events were registered. In men, the highest ranking risk factors for coronary heart disease were vital exhaustion [high vs. low; hazard ratio (HR) 2.36; 95% confidence interval (CI), 1.70-3.26; P < 0.001] and systolic blood pressure (≥160 mmHg or blood pressure medication vs. <120 mmHg; HR 2.07; 95% CI, 1.48-2.88; P < 0.001). In women, smoking was of highest importance (≥15 g tobacco/day vs. never smoker; HR 1.74; 95% CI, 1.43-2.11; P < 0.001), followed by vital exhaustion (high vs. low; HR 2.07; 95% CI, 1.61-2.68; P < 0.001). Vital exhaustion ranked first in women and fourth in men by population attributable fraction of 27.7% (95% CI, 18.6-36.7%; P < 0.001) and 21.1% (95% CI, 13.0-29.2%; P < 0.001), respectively. Finally, vital exhaustion significantly improved risk prediction., Conclusion: Vital exhaustion was one of the most important risk factors for coronary heart disease, our findings emphasize the importance of including psychosocial factors in risk prediction scores., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: Mortality from ischaemic heart disease (IHD) including acute myocardial infarction (AMI) in Denmark peaked around 1977, after which a marked decline has occurred as a result of decreasing incidence and increasing effect of treatment. IHD is a chronic, relapsing condition, and the effect of these changes on the prevalence of IHD is not known., Methods and Results: Changes in incidence and prevalence in 2000-2009 are presented, using nationwide data from public registers. An incident case is defined as a subject registered with a diagnosis of IHD/AMI and without a prior diagnosis for the past 20 years (beginning in 1980). A prevalent case is defined as a subject surviving the first year after the incident diagnosis. Regarding IHD, age-standardised incidence rates declined significantly from 2000 to 2009 for both sexes (females 445 to 340/100,000, males 822 to 678/100,000), reflecting a reduction in the annual number of new cases from 19.345 to 16.757. In contrast, prevalence rates increased slightly (females 2389 to 2616/100,000, males 5447 to 5579/100,000). Due to an increased proportion of elderly in the population, the number of prevalent cases increased from 125,000 in 2000 to 150,000 in 2009. The number of subjects having survived an AMI increased from 67,000 to 72,000. About 3% of the Danish population is afflicted by IHD., Conclusion: Decreasing incidence, reduced case fatality and demographic development result in an increased prevalence of IHD, since the decline in incidence is more than offset by a larger decline in case fatality. The epidemic of IHD is far from over, in spite of the marked success of prevention and treatment., (© The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Aims: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with substantial morbidity and mortality. AF is associated with enlargement of the left atrium (LA), and the LA volume has important prognostic implications for the disease. The objective of the study was to determine how measurements of LA volume and function obtained by transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and 320-slice multi-detector computed tomography (MDCT) correlate in patients with permanent AF., Methods and Results: Thirty-four patients with permanent AF participated in the study. TTE, CMR, and 320-slice MDCT imaging procedures were performed within 7 ± 4 days. 320-slice MDCT overestimated maximal LA volume (LAmax) and minimal LA volume (LAmin) compared with CMR (LAmax: 80 vs. 73 mL/m(2), P = 0.0017; LAmin: 69 vs. 64 mL/m(2), P = 0.0217), whereas TTE underestimated these parameters compared with CMR (LAmax: 60 vs. 73 mL/m(2), P < 0.0001; LAmin: 50 vs. 64 mL/m(2), P < 0.0001), and also compared with MDCT (LAmax: 60 vs. 80 mL/m(2), P < 0.0001; LAmin: 50 vs. 69 mL/m(2), P < 0.0001). Measurements of LA volumes by MDCT and CMR closely correlated, and both MDCT and CMR had excellent intra- and inter-observer agreement with correlation coefficients of >0.90. The correlation between TTE-derived measurements and CMR/MDCT was fair to moderate. Intra- and inter-observer agreement for LA volume measurements by TTE were inferior to CMR and MDCT., Conclusion: Measurements of LA volumes by CMR and 320-slice MDCT correlate closely in patients with permanent AF, and both modalities improve the reproducibility of measurements of LA volumes and function compared with 2D TTE.

Since 1970, jogging has become an increasingly popular form of exercise, but concern about harmful effects has been raised following reports of deaths during jogging. The purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women. Jogging habits were recorded in a random sample of 17,589 healthy men and women aged 20-98 years, invited between 1976 and 2003 to the Copenhagen City Heart Study. The expected lifetime was calculated by integrating the predicted survival curve estimated in the Cox model. In this study 1,878 persons (1,116 men and 762 women) were classified as joggers. During the 35-year maximum follow-up period, we registered 122 deaths among joggers and 10,158 deaths among nonjoggers. The age-adjusted hazard ratio of death among joggers was 0.56 (95% confidence interval: 0.46, 0.67) for men and 0.56 (95% confidence interval: 0.40, 0.80) for women. The age-adjusted increase in survival with jogging was 6.2 years in men and 5.6 years in women. This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women.

Aims: To determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population., Methods and Results: We followed 18 441 participants included in the Copenhagen City Heart Study examined in 1976-2003 free from previous myocardial infarction (MI), chronic heart failure, and left bundle branch block through registry linkage until 2009 for all-cause mortality and cardiovascular outcomes. The prevalence of RBBB/IRBBB was higher in men (1.4%/4.7% in men vs. 0.5%/2.3% in women, P < 0.001). Significant predictors of newly acquired RBBB were male gender, increasing age, high systolic blood pressure, and presence of IRBBB, whereas predictors of newly acquired IRBBB were male gender, increasing age, and low BMI. Right bundle branch block was associated with significantly increased all-cause and cardiovascular mortality in both genders with age-adjusted hazard ratios (HR) of 1.31 [95% confidence interval (CI), 1.11-1.54] and 1.87 (95% CI, 1.48-2.36) in the gender pooled analysis with little attenuation after multiple adjustment. Right bundle branch block was associated with increased risk of MI with an HR of 1.67 (95% CI, 1.16-2.42) and pacemaker insertion with an HR of 2.17 (95% CI, 1.22-3.86), but not with chronic heart failure (HR 1.37; 95% CI, 0.96-1.94), atrial fibrillation (HR 1.10; 95% CI, 0.73-1.67), or chronic obstructive pulmonary disease (HR 0.99; 95% CI, 0.60-1.62). The presence of IRBBB was not associated with any adverse outcome., Conclusion: In this cohort study, RBBB and IRBBB were two to three times more common among men than women. Right bundle branch block was associated with increased cardiovascular risk and all-cause mortality, whereas IRBBB was not. Contrary to common perception, RBBB in asymptomatic individuals should alert clinicians to cardiovascular risk.

Aims: To investigate the association between resting heart rate (RHR) and markers of chronic low-grade inflammation. Also, to examine whether elevated resting heart rate is independently associated with cardiovascular and all-cause mortality in the general population, or whether elevated RHR is merely a marker of chronic low-grade inflammation., Methods and Results: A group of 6518 healthy subjects from the the Danish general population were followed for 18 years during which 1924 deaths occurred. Subjects underwent assessment of baseline RHR, conventional cardiovascular risk factors, high-sensitivity C-reactive protein (hsCRP), and fibrinogen. RHR was associated with hsCRP and fibrinogen in uni- and multivariate models (p < 0.0001). A 10 beats per minute increase in RHR was associated with increased cardiovascular and all-cause mortality in univariate models - HR (95%CI) (1.21 (1.14-1.29) and 1.15 (1.11-1.19); multivariate models adjusted for conventional risk factors - 1.16 (1.09-1.24) and 1.10 (1.06-1.14); multivariate models including hsCRP - 1.14 (1.07-1.22) and 1.09 (1.05-1.14); fibrinogen - 1.15 (1.07-1.22) and 1.09 (1.05-1.14); and both hsCRP and fibrinogen - 1.14 (1.07-1.22) and 1.09 (1.05-1.14)., Conclusion: RHR was associated with markers of chronic low-grade inflammation. However, RHR remained associated with both cardiovascular and all-cause mortality after adjusting for markers of chronic low-grade inflammation. This suggests that RHR is an independent risk factor for cardiovascular and all-cause mortality, and not merely a marker of chronic low-grade inflammation.

Background: Current recommendations prescribe that every adult should accumulate 30 minutes or more of moderate physical activity in leisure time, preferably every day of the week. The optimal intensity, duration, and frequency still have to be established. The aim of this study was to examine the impact of intensity versus duration of cycling on all-cause and coronary heart disease mortality., Design: Relative intensity and duration of cycling were recorded in 5106 apparently healthy men and women aged 21-90 years drawn from the general population of Copenhagen, and followed for an average of 18 years. Total number of deaths during follow-up was 1172, of these 146 were coronary heart disease deaths. For both sexes we found a significant inverse association between cycling intensity and risk of all-cause and coronary heart disease death, but only a weak association with cycling duration. The difference in expected lifetime in relation to intensity of cycling was calculated. Men with fast intensity cycling survived 5.3 years longer, and men with average intensity 2.9 years longer than men with slow cycling intensity. For women the figures were 3.9 and 2.2 years longer, respectively., Conclusion: Our findings indicate that the relative intensity, and not the duration of cycling, is of more importance in relation to all-cause and coronary heart disease mortality. Thus our general recommendations to all adults would be that brisk cycling is preferable to slow.

Aims: The prevalence of the Brugada-type electrocardiogram (ECG) in the Danish population is not known., Methods and Results: Inhabitants from the city of Copenhagen, Denmark, have participated in a prospective study since 1976. Four cross-sectional surveys have been carried out. Follow-up was performed using public registers. At each examination, the participants had an ECG registered. ECGs, showing right bundle branch block (RBBB) were examined for a possible Brugada-type pattern. A total of 42,560 ECGs had been registered from 18,974 participants. 1,284 had been coded as RBBB. Among these ECGs, we found no ECGs showing type 1 Brugada pattern, and 14 showing type 2 or 3 pattern. The prevalence of the total number of ECGs with Brugada pattern was 7/10,000. None of the subjects with a Brugada-pattern ECG died suddenly during follow-up., Conclusion: The Brugada-type ECG pattern is rare in the general Danish population. None of the subjects with a Brugada-type ECG died suddenly during a follow-up of 6-33 years.

Background: Chronic stress may affect morbidity and mortality through neuroendocrine changes, and the ratio of cortisol to sex steroid hormones has been suggested as a biomarker of stress. We aim to address a relation between the ratio of cortisol to estrogens (C/E) and risk of ischaemic heart disease (IHD), hormone-dependent cancers and all-cause mortality among postmenopausal women., Methods: Estradiol and cortisol were measured in a subset of 838 women randomly drawn from the second wave of the Copenhagen City Heart Study (n = 5297 examined in 1981-83) as well as among all women who developed hormone-dependent cancers after baseline. The participants were followed in nationwide registers until 2007, with < 0.1% loss to follow-up., Results: The C/E ratio was not associated with self-reported stress, and there were no clear associations with IHD (highest vs lowest quartile: HR = 1.23; 95% confidence interval 0.83-1.81), hormone-dependent cancers (0.69; 0.45-1.08) or all-cause mortality (1.10; 0.86-1.41)., Conclusions: The C/E ratio was not associated with morbidity and mortality in women, and we cannot replicate the robust findings of a relation between the cortisol to testosterone ratio and IHD previously reported in men. Whether the C/E ratio is a reasonable biomarker of stress is debatable.

Background: Leptin and adiponectin are hormones secreted by adipose tissue, and both hormones are candidate intermediaries between adipose tissue and overweight-related diseases. So far, no prospective study has been published where the independent effects of these two hormones on the development of hypertension have been directly compared. The objective of this study was to investigate the relationships between plasma levels of leptin and adiponectin and new-onset hypertension in the Copenhagen City Heart Study (CCHS)., Methods: In a prospective study design, we examined new-onset hypertension in 620 women and 300 men who were normotensive in the third CCHS examination, which was performed in 1991-1994., Results: Between the third and the fourth CCHS examination, which was performed in 2001-2003, 254 had developed hypertension, defined as systolic blood pressure (SBP) > or = 140 mm Hg, or diastolic blood pressure (DBP) > or = 90 mm Hg, or use of antihypertensive medication. Using logistic regression analysis, adjusting for age, sex, estimated glomerular filtration rate, triglycerides, high-density lipoprotein cholesterol (HDL-C), fibrinogen, and glucose, and with leptin and adiponectin included in the same model, leptin was significantly associated with new-onset hypertension with an odds ratio (95% confidence interval) of 1.28 (1.08-1.53; P < 0.005) for 1 s.d. higher level of log-transformed leptin, whereas adiponectin was not significantly associated with new-onset hypertension having an odds ratio of 1.02 (0.84-1.24; P = 0.83) for 1 s.d. higher level of log-transformed adiponectin., Conclusions: In the CCHS, leptin, but not adiponectin, was a significant independent predictor of new-onset hypertension.

Context: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease)., Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and -480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD., Design: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete., Results: HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in -480c>t heterozygotes, and by 0.13 mmol/liter in -480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84-0.90], 0.96 (95% CI 0.95-0.97), and 0.91 (95% CI 0.89-0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76-1.88), 1.04 (0.96-1.13), and 1.08 (0.89-1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0., Conclusion: Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD.

Background: Low-grade chronic inflammation has been proposed to play a major role in the pathogenesis of hypertension. Low-grade chronic inflammation is also closely associated with obesity, an established causative factor in the development of hypertension. The purpose of this study was to investigate the relationship between two markers of inflammation, C-reactive protein (CRP) and fibrinogen, and blood pressure (BP) and other hemodynamic variables in obese subjects., Methods: From a large cardiovascular study based in the general population, we selected subjects with a body mass index (BMI) > or =30 kg/m2, free of major cardiovascular diseases, not taking BP-lowering or lipid-lowering drugs (n = 487; women = 51.1%; median (5th to 95th percentile) age = 62 years (36-80)). The cardiovascular study included measurements of traditional and new risk factors, including ankle brachial BP index, a measure of subclinical atherosclerosis. CRP was determined by a high-sensitive assay., Results: In partial Spearman rank correlation analysis, adjusted for age and sex, we found no significant relationships between either CRP or fibrinogen and systolic BP, diastolic BP, pulse pressure, or ankle brachial index (rho: -0.057 to 0.068; P > 0.13). However, fibrinogen and CRP were found to be significantly related to heart rate (rho: 0.127-0.169; P < 0.01)., Conclusions: In this study of generally healthy obese subjects from the general population, we found no significant relationships between markers of inflammation and systolic BP or diastolic BP, showing that obese subjects with higher levels of inflammatory markers do not have higher BP levels than their obese counterparts with lower levels of inflammatory markers.

Context: We have previously shown that rare mutations in the apolipoprotein B gene (APOB) may result in not only severe hypercholesterolemia and ischemic heart disease but also hypocholesterolemia. Despite this, common single-nucleotide polymorphisms (SNPs) in APOB have not convincingly been demonstrated to affect low-density lipoprotein (LDL) cholesterol levels., Objective: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease., Design: This was a prospective study with 25 yr 100% follow up, The Copenhagen City Heart Study., Setting: The study was conducted in the Danish general population., Participants: Participants included 9185 women and men aged 20-80+ yr., Main Outcome Measures: Levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease and myocardial infarction were measured. The hypothesis was formulated before genotyping., Results: We genotyped 9185 individuals for APOB T71I (minor allele frequency: 0.33), Ivs4+171c>a (0.14), A591V (0.47), Ivs18+379a>c (0.30), Ivs18+1708g>t (0.45), T2488Tc>t (0.48), P2712L (0.21), R3611Q (0.09), E4154K (0.17), and N4311S (0.21). SNPs were associated with increases (T71I, Ivs181708g>t, T2488Tc>t, R3611) or decreases (Ivs4+171c>a, A591V, Ivs18+379a>c, P2712L, E4154, N4311S) in LDL cholesterol from -4.7 to +8.2% (-0.28 to 0.30 mmol/liter; P

Context: Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)., Objective: The objective of this study was to investigate the influence of T(-93)G, G(-53)C, Asp9Asn, Gly188Glu, Asn291Ser, and Ser447Ter lipoprotein lipase genotypes on triglycerides, HDL, and IHD., Design: The cross-sectional study involved 9004 adults. The prospective study consisted of 8817 adults developing 1001 IHD events over 23 yr. The case-control study involved 7818 non-IHD individuals vs. cohorts of 915 and 1062 IHD patients, respectively., Setting: The study was performed in the Danish general population (the Copenhagen City Heart Study)., Participants: IHD was angina pectoris or myocardial infarction., Main Outcome Measures: Triglycerides, HDL, and IHD were the main outcome measures., Results: Cross-sectionally, triglycerides varied by genotype with 1.27 mmol/liter in women and 1.22 mmol/liter in men. HDL cholesterol varied by genotype with 0.49 mmol/liter in women and 0.60 mmol/liter in men. Prospectively, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had a hazard ratio for IHD of 1.6 [95% confidence interval (CI), 1.2-2.3]; 291Ser and 447Ter did not change IHD risk. In the case-control study, combining the cohorts of IHD patients, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had an odds ratio for IHD of 1.5 (CI, 1.2-2.1). 291Ser and 447Ter did not change IHD risk. Stratified for apolipoprotein E genotype, the odds ratios for IHD in 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers were 2.6 (CI, 1.2-5.5) among epsilon32 individuals and 2.4 (CI, 1.4-4.1) among epsilon43 individuals., Conclusions: Genetic variation in lipoprotein lipase is associated with differences in plasma triglycerides greater than 1 mmol/liter and differences in HDL cholesterol greater than 0.5 mmol/liter. A 1.6-fold risk of IHD in 9Asn (with -93G) heterozygotes and homozygotes combined is influenced by apolipoprotein E genotype.