Non-fatal CHD Research Articles

Circulating Omega-3 Polyunsaturated Fatty Acids Levels in Coronary Heart Disease: Pooled Analysis of 36 Observational Studies.

Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study. We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools. n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.

Psychological stress, body shape and cardiovascular events: Results from the Whitehall II study

Background and aimIt is known that persistent psychological stress predicts changes in body shape in two different ways: some stressed people lose weight, others gain weight. It is also known that persistent psychological stress predicts adverse health events. But it is unknown what role the body shape plays in this particular network of relationships. We therefore analyzed the Whitehall II dataset to relate body shape to stress and health risk. MethodsData of 4969 men and 2138 women from the Whitehall II cohort were analyzed. Psychological stress (General Health Questionnaire) was measured three times in the years 1991 till 2001. Body shape (BMI, waist and hip circumferences) was measured in the years 1991 till 1994. Childhood adversities were retrospectively assessed by questionnaire. Outcomes included the incidence of non-fatal or fatal CHD events (coronary heart disease) collected up to the years 2012 and 2013 and all-cause mortality collected up to July 2015. Cox proportional hazard models were conducted to estimate the relation between psychological stress and CHD events or all-cause mortality. ResultsThere was an increase in the expected hazard to develop CHD with high psychological stress (men: Exp (B) = 1.25 (1.06–1.47); P = 0.008; women: Exp (B) = 1.34 (1.05–1.70); P = 0.017). We found a clear dose-response relationship for the association between psychological stress and CHD events in both genders. That is, subjects with consistently high psychological stress in all assessments had a 2.4-fold (men) or 2.3-fold (women) higher risk for later CHD events compared to never-stressed subjects. Moreover, subjects with a high sum score of all 13 childhood experiences had a 10% increased hazard to develop fatal or non-fatal CHD events in adulthood. Although we could not find stress or BMI linked to all-cause mortality, the waist-to-hip ratio contributed to the risk of all-cause mortality in both genders (Exp (B) = 34.66 (6.43–186.92); P < 0.001 for men; Exp (B) = 60.65 (9.33–394.22); P < 0.001 for women). ConclusionThis analysis supports the notion that psychological stress and childhood adversities are associated with the risk of fatal or non-fatal CHD events. When this relationship is analyzed in more detail, the Whitehall II dataset provides further insights into the role of body shape. That is, stress is also related to changes in body shape, with waist size in particular predicting higher all-cause mortality.

Intake of carbohydrates and SFA and risk of CHD in middle-age adults: the Hordaland Health Study (HUSK).

Limiting SFA intake may minimise the risk of CHD. However, such reduction often leads to increased intake of carbohydrates. We aimed to evaluate associations and the interplay of carbohydrate and SFA intake on CHD risk. Prospective cohort study. We followed participants in the Hordaland Health Study, Norway from 1997-1999 through 2009. Information on carbohydrate and SFA intake was obtained from a FFQ and analysed as continuous and categorical (quartiles) variables. Multivariable Cox regression estimated hazard ratios (HR) and 95 % CI. Theoretical substitution analyses modelled the substitution of carbohydrates with other nutrients. CHD was defined as fatal or non-fatal CHD (ICD9 codes 410-414 and ICD10 codes I20-I25). 2995 men and women, aged 46-49 years. Adjusting for age, sex, energy intake, physical activity and smoking, SFA was associated with lower risk (HRQ4 v. Q1 0·44, 95 % CI 0·26, 0·76, Ptrend = 0·002). For carbohydrates, the opposite pattern was observed (HRQ4 v. Q1 2·10, 95 % CI 1·22, 3·63, Ptrend = 0·003). SFA from cheese was associated with lower CHD risk (HRQ4 v. Q1 0·44, 95 % CI 0·24, 0·83, Ptrend = 0·006), while there were no associations between SFA from other food items and CHD. A 5 E% substitution of carbohydrates with total fat, but not SFA, was associated with lower CHD risk (HR 0·75, 95 % CI 0·62, 0·90). Higher intake of predominantly high glycaemic carbohydrates and lower intake of SFA, specifically lower intake from cheese, were associated with higher CHD risk. Substituting carbohydrates with total fat, but not SFA, was associated with significantly lower risk of CHD.

Reduction in saturated fat intake for cardiovascular disease.

Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019. Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available. Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment. We included 15 randomised controlled trials (RCTs) (16 comparisons, 56,675 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 17% (risk ratio (RR) 0.83; 95% confidence interval (CI) 0.70 to 0.98, 12 trials, 53,758 participants of whom 8% had a cardiovascular event, I² = 67%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 53. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes. The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

Reduction in saturated fat intake for cardiovascular disease.

Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019. Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available. Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment. We included 15 randomised controlled trials (RCTs) (16 comparisons, ~59,000 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 21% (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.66 to 0.93, 11 trials, 53,300 participants of whom 8% had a cardiovascular event, I² = 65%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 32. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes. The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

Intake of fermented and non-fermented dairy products and risk of incident CHD: the Kuopio Ischaemic Heart Disease Risk Factor Study.

Recent dairy product studies have suggested that fermented rather than non-fermented dairy products might provide benefits on cardiovascular health, but the evidence is inconclusive. Therefore, we investigated whether fermented and non-fermented dairy products have distinct associations with the risk of incident CHD in a population with high dairy product intake. The present study included a total of 1981 men, aged 42-60 years, from the Kuopio Ischaemic Heart Disease Risk Factor Study, with no CHD at baseline. Dietary intakes were assessed with instructed 4-d food records. We used Cox's proportional hazards regression model to estimate the associations with the risk of CHD. Fatal and non-fatal CHD events were ascertained from national registries. During a mean follow-up of 20·1 years, 472 CHD events were recorded. Median intakes were 105 g/d for fermented (87 % low-fat products) and 466 g/d for non-fermented dairy products (60 % low-fat products). After adjusting for potential confounders, those in the highest (v. lowest) intake quartile of fermented dairy products had 27 % (95 % CI 5, 44; P-trend=0·02) lower risk of CHD. In contrast, those in the highest intake quartile of non-fermented dairy products had 52 % (95 % CI 13, 104; P-trend=0·003) higher risk of CHD. When analysed based on fat content, low-fat (<3·5 % fat) fermented dairy product intake was associated with lower risk (hazard ratio in the highest quartile=0·74; 95 % CI 0·57, 0·97; P-trend=0·03), but high-fat fermented dairy and low-fat or high-fat non-fermented dairy products had no association. These results suggest that fermented and non-fermented dairy products can have opposite associations with the risk of CHD.

Dietary patterns within educational groups and their association with CHD and stroke in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort.

Higher-educated people often have healthier diets, but it is unclear whether specific dietary patterns exist within educational groups. We therefore aimed to derive dietary patterns in the total population and by educational level and to investigate whether these patterns differed in their composition and associations with the incidence of fatal and non-fatal CHD and stroke. Patterns were derived using principal components analysis in 36 418 participants of the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Self-reported educational level was used to create three educational groups. Dietary intake was estimated using a validated semi-quantitative FFQ. Hazard ratios were estimated using Cox Proportional Hazard analysis after a mean follow-up of 16 years. In the three educational groups, similar 'Western', 'prudent' and 'traditional' patterns were derived as in the total population. However, with higher educational level a lower population-derived score for the 'Western' and 'traditional' patterns and a higher score on the 'prudent' pattern were observed. These differences in distribution of the factor scores illustrate the association between education and food consumption. After adjustments, no differences in associations between population-derived dietary patterns and the incidence of CHD or stroke were found between the educational groups (P interaction between 0·21 and 0·98). In conclusion, although in general population and educational groups-derived dietary patterns did not differ, small differences between educational groups existed in the consumption of food groups in participants considered adherent to the population-derived patterns (Q4). This did not result in different associations with incident CHD or stroke between educational groups.

Abstract P316: Multiple Vulnerabilities to Health Disparities and Incident Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Social determinants contribute to disparities in incident CHD but it is not known if they have an additive effect. We hypothesized that having more socially determined vulnerabilities to health disparities is associated with increased risk of incident CHD in the REGARDS study, a large biracial prospective cohort with physiological and survey measures. Experts adjudicated incident fatal and nonfatal CHD over 10 years of follow-up. Vulnerabilities included black race, low education, low income, and Southeastern US residence. The risks for CHD outcomes associated with 1, 2, and 3+ vs 0 vulnerabilities were calculated with Cox proportional hazards models adjusted for medical conditions, functional status, health behaviors, and physiologic variables. Of the 19,645 participants free of CHD at baseline (mean age 64 years, 57% women), 16% had 0 vulnerabilities, 36% had 1, 29% had 2, and 18% had 3+. Increasing numbers of vulnerabilities were associated with higher incidence (Figure) and risk of CHD that attenuated somewhat after multivariable adjustment (Table). These findings may provide a method of risk stratification useful for population health management.

Clinical characteristics of Chinese patients with duration of type 2 diabetes >40 years.

Although type 2 diabetes mellitus (T2DM) shortens life expectancy by 10-12 years, some patients survive extremely long durations of diabetes. The clinical characteristics of Chinese patients with >40 years T2DM remain unknown. Thus, the aim of the present study was to document the clinical profile of patients with T2DM for ≥40 years. The present study evaluated 157 survivors with >40 years T2DM from a total of 582 773 patients with T2DM enrolled in a Chinese national survey of HbA1c. Two matched case-control studies were performed on long T2DM survivors (cases) separately matched according to: (1) survey day, sex, and survey hospital; and (2) age, sex, and survey hospital. Conditional logistic regression analysis was performed to obtain odds ratios (ORs) for long survival. Patients with a long duration of T2DM had a mean (± SD) age of 75 ± 10 years. Their T2DM had been diagnosed at a mean age of 32 years and the median duration of diabetes was 41 years. In both case-control studies, long-duration T2DM was associated with an increased risk of hyperglycemia (OR 6.31; 95% confidence interval [CI] 1.89-21.09) and coronary heart disease (CHD; OR 2.18 95% CI 1.01-4.70). However, long-duration T2DM was not associated with a higher likelihood of abnormal lipids, diabetic nephropathy (DN), or stroke compared with patients with a shorter duration of T2DM. The present study suggests that Chinese patients with long-term T2DM also had increased risks of hyperglycemia and non-fatal CHD. Further studies are needed to investigate whether survival of these patients was associated with non-increased risk of DN.

Abstract MP07: Racial Differences in Incident CHD in Observational Population-based Studies

Background: In the modern era, black men have twice the risk for fatal CHD versus white men, with similar incidence of total CHD. To examine secular trends in these findings, we compared the risk for incident fatal, nonfatal and total CHD by race across three US cohorts from different time periods. Methods: We analyzed data from blacks and whites in the Atherosclerosis Risk In Communities (ARIC) study (n=14,967, all 45-64 years of age, baseline 1987-1989), the Cardiovascular Health Study (CHS, n=4,626, all ≥65 years of age, baseline 1989-1993) and the REasons for Geographic and Racial Differences in Stroke (REGARDS) study (13,115 participants 45-64 years of age, 7,493 participants ≥65 years of age, baseline 2003-2007) who were free of CHD at baseline. Participants were followed for up to 10 years for fatal or nonfatal CHD. Analyses were stratified by age and gender and adjusted for similar risk factors across cohorts. Results: After age adjustment, black men 45-64 years of age in ARIC and REGARDS had higher risk for fatal CHD and similar risk for nonfatal and total CHD compared with their white counterparts (Table). After further adjustment for risk factors, blacks had similar risk for fatal CHD and lower risk for nonfatal and total CHD. A higher age-adjusted risk for fatal CHD and lower multivariable-adjusted risk for nonfatal CHD was also found among black versus white men ≥65 years of age in REGARDS; however, these associations were attenuated/absent in CHS. Among women 45-64 years of age in ARIC and REGARDS, blacks had higher age-adjusted risk for fatal, nonfatal and total CHD which were attenuated after adjustment for risk factors. There was no association between black race and CHD among women ≥65 years of age. Conclusion: Black-white disparities in the incidence of fatal CHD have remained similar for many years, particularly among those &lt;65 years of age, and are explained by risk factors. The higher risk for fatal CHD is more striking among black men who consistently shown similar risk for total CHD compared with white men across cohorts.

Abstract MP44: Lifetime Marijuana Use is Not Associated with Incident Cardiovascular Disease in Middle-Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Marijuana is the most frequently used illicit drug in the US. Its use is expected to rise given recent state policies that relax criminalization and permit medicinal use. Although several mechanisms exist by which marijuana might contribute to chronic cardiovascular conditions, few data are available. We sought to determine the association of lifetime marijuana use with the development of incident CHD and CVD. Methods: Participants were 5,114 white and black adults aged 18-30 years in 1985-86 from the multicenter, community-based CARDIA Study who have been followed for over 25 years. We estimated cumulative years of exposure in “marijuana-years,” with one marijuana-year equal to 365 days of marijuana use using repeated assessments every 2-5 years. Incident CHD included fatal or nonfatal myocardial infarction, angina, or CHD death. Incident CVD included CHD, stroke, hospitalized heart failure, and intervention for peripheral arterial disease. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. Lifetime marijuana use and all time-varying covariates were entered as time-dependent variables. Results: Approximately 16% of the cohort were lifetime never users of marijuana, while 35%, 22%, 14%, and 13% reported lifetime use of &lt;0.5, 0.5-&lt;2, 2-&lt;5, and ≥5 marijuana-years, respectively. During a median of 26.9 years of follow-up (132,120 person-years), there were 104 and 216 cases of CHD and CVD, respectively. Compared to never use, categories of lifetime marijuana use showed no evidence for a higher or lower risk for CHD or CVD, regardless of the level of multivariable adjustment (Table). Findings did not vary significantly by age, sex, race, family history, 10-year risk of CVD, or use of other illicit drugs (p-interaction &gt;0.3, for all). Conclusions: In this long-term follow-up study of young adults at baseline, lifetime use of marijuana at these levels was not associated with incident CHD or CVD in middle-age.

Abstract 19268: Robust Performance of LpPLA2 Activity in Predicting Cardiovascular Disease Risk in a National, Diverse, Sample

Introduction: LpPLA2 activity increases in inflamed plaques associated with atherosclerotic disease. Elevated circulating LpPLA2 is associated with increased risk of cardiovascular disease but it is not known whether this risk is consistent across demographic and risk groups. Methods: We developed a case cohort study within the REasons for Geographic and Racial Disparities in Stroke (REGARDS) study. We included a random cohort sample (n=3719) derived from the 23,019 REGARDS participants who were free from stroke and cardiovascular disease at baseline in 2003-7. We used weighted Cox models to study the association between LpPLA2 activity and risk of cardiovascular disease. Acute CHD during complete follow up through 12/31/2010 was adjudicated by an expert committee and defined as definite or probable myocardial infarction (MI) not resulting in death within 28 days (nonfatal acute CHD) or fatal acute CHD. LpPLA2 activity was measured using the PLAC® Activity Test at Diadexus. LpPLA2 activity was dichotomized at the 80th percentile of gender specific activity. The cut-off for men was 250 and for women was 200 nmol/ml/min. Results: The cohort included black (46%) and white (54%) participants over age 45 and was 42% male. 565 cases of acute CHD were available for analysis. After controlling for race, age, sex, statin use, income, education, lipid profile, hypertension, diabetes, and history of smoking, elevated LpPLA2 activity was associated with increased risk of cardiovascular disease HR=1.52; 95% CI (1.21, 1.91). This result was consistent and not significantly different across demographic and risk categories (Table).The Net Reclassification Index was 13%, p&lt;0.001. Conclusions: LpPLA2 activity is associated with increased risk of cardiovascular disease among black and white men and women. The increased risk is observed even in participants at low risk of cardiovascular disease as defined by the Framingham risk function.

Abstract 20: Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: the Cardiovascular Health Study

Background: While omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including depending on types of n-6 PUFA and diseases examined. Aims: To assess associations of circulating n-6 PUFA including linoleic acid (LA, the major dietary PUFA), Γ-linoleic acid (GLA), dihomo-Γ-linoleic acid (DGLA), and arachidonic acid (AA),with incident total and cause-specific mortality in the Cardiovascular Health Study (CHS), a community-based US cohort. Methods: Among 2,692 participants age≥65y and free of CVD at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total (fatal or nonfatal) incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA biomarkers with risk were assessed by multivariable Cox regression. Results: During 33,091 person-years of follow-up (1992-2010), 1920 deaths occurred (including 660 cardiovascular deaths), as well as 414 fatal and 410 nonfatal CHD events, and 150 fatal and 384 nonfatal strokes. In multivariable models, higher LA was associated with lower risk of total mortality, with extreme quintile HR 0.84 (95% CI 0.71-0.98, P- trend 0.002). Lower death was largely attributable to CVD rather than non-CVD causes, especially nonarhythmic CHD mortality (HR 0.50, 95% CI 0.31-0.80, P- trend 0.001). Phospholipid GLA, DGLA, and AA levels were not associated with total or cause-specific mortality; e.g., for AA and CHD death, the extreme quintile HR was 0.98 (95% CI 0.71-1.37, P- trend 0.72). Evaluated semi-parametrically, LA showed graded (monotonic) inverse associations with total mortality ( Figure 1A ). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA (Bonferroni corrected P =NS, Figure 1B ). Conclusion: Higher circulating LA, but not other n-6 PUFA, is inversely associated with total and CHD mortality in older adults.

Abstract P367: Primordial Prevention of Coronary Heart Disease through Healthy Lifestyle in a Large Prospective Cohort of Young Women

Background: Although overall mortality rates from CHD in the U.S. have continued to decline in recent decades, the CHD mortality rate among women 35 to 54 years old has been increasing on average by 1.5% per year since 1997. This unfavorable trend may be explained, in part, by adverse lifestyle habits among younger adults. The purpose of this analysis was to estimate the burden of CHD among younger women that can be attributed to lack of adherence to a healthy lifestyle. Methods and Results: We conducted a prospective analysis among 93,161 women, 27-44 years of age at baseline, enrolled in the Nurses’ Health Study II cohort and followed from 1991 to 2009. Lifestyle factors were assessed repeatedly during follow-up by questionnaire. Healthy lifestyle was defined as not currently smoking, having a BMI of 18.5 [[Unable to Display Character: &amp;#8211;]] 24.9 kg/m 2 , engaging in at least 2.5 hours/week of moderate to vigorous-intensity physical activity, having a diet in the top 40% of Alternative Healthy Eating Index-2010, and consuming 5 [[Unable to Display Character: &amp;#8211;]] 30g/day of alcohol. To estimate the proportion of CHD that could be attributed to poor adherence to a healthy lifestyle, we calculated the population attributable risk percent. During follow-up, we documented 441 new cases of non-fatal MI and fatal CHD. After adjustment for other CVD risk factors, non-smoking, healthy BMI, exercise, and healthy diet were independently and significantly associated with lower CHD risk. Compared to women with 0 healthy lifestyle factors, the hazard ratio (HR) for CHD was 0.07 (95% CI, 0.03, 0.17) for women with all 5 healthy lifestyle factors (4% of the study population). Approximately 67% (95% CI 28%, 87%) of CHD cases in this population were attributable to poor adherence to a healthy lifestyle. Among non-smokers, 59% (95% CI 13%, 84%) of CHD cases were attributable to poor adherence to the other four healthy lifestyle factors. Conclusions: Primordial prevention through maintenance or adoption of a healthy lifestyle may lower incidence of CHD and potentially reverse the unfavorable trend in CHD mortality in younger women.

Fish consumption and the risk of myocardial infarction and stroke in the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Germany)

Recent meta-analyses have confirmed that fish consumption is related to decreased risks of ischaemic stroke and fatal CHD, while there seem to be no clear associations between fish consumption and the risks of haemorrhagic stroke and non-fatal CHD. As no studies in German populations have been reported to date, we assessed whether fish consumption as recorded by FFQ between 1994 and 1998 was related to incident myocardial infarction (MI) and stroke within the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression analyses were conducted based on the data of 48 315 participants aged 35–65 years at baseline. The median fish intake was 16·4 g/d (25th–75th percentile 8·2–28·8 g/d). During a mean follow-up of 8·1 years, 605 incident MI and 525 incident strokes have been documented. After multiple adjustment, fish consumption was not related to incident MI (hazard ratio (HR) 0·84, 95 % CI 0·66, 1·08, P trend= 0·21) or stroke (HR 0·96, 95 % CI 0·73, 1·26, P trend= 0·67). Separate analyses for fatal MI, ischaemic stroke and haemorrhagic stroke did not show significant associations, either. With regard to non-fatal MI, there was a non-significant trend for an inverse association (HR 0·78, 95 % CI 0·59, 1·03, P trend= 0·07). Overall, fish consumption was not related to the risks of MI and stroke in the EPIC-Germany study.

Statins for the primary prevention of cardiovascular disease.

Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of CVD is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with CVD. The case for primary prevention was uncertain when the last version of this review was published (2011) and in light of new data an update of this review is required. To assess the effects, both harms and benefits, of statins in people with no history of CVD. To avoid duplication of effort, we checked reference lists of previous systematic reviews. The searches conducted in 2007 were updated in January 2012. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2022, Issue 4), MEDLINE OVID (1950 to December Week 4 2011) and EMBASE OVID (1980 to 2012 Week 1).There were no language restrictions. We included randomised controlled trials of statins versus placebo or usual care control with minimum treatment duration of one year and follow-up of six months, in adults with no restrictions on total, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD. Two review authors independently selected studies for inclusion and extracted data. Outcomes included all-cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), revascularisation, change in total and LDL cholesterol concentrations, adverse events, quality of life and costs. Odds ratios (OR) and risk ratios (RR) were calculated for dichotomous data, and for continuous data, pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated. We contacted trial authors to obtain missing data. The latest search found four new trials and updated follow-up data on three trials included in the original review. Eighteen randomised control trials (19 trial arms; 56,934 participants) were included. Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non-fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no evidence of any serious harm caused by statin prescription. Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event. Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins.

Don't disregard the essential distinction between PUFA species

Don't disregard the essential distinction between PUFA species

Impact of low v. moderate intakes of long-chain n-3 fatty acids on risk of coronary heart disease

The objective of the present study was to determine whether the consumption of≥250 v. <250mg of the long-chain n-3 fatty acids (n-3 LCFA) per d is associated with a reduction in the risk of fatal and non-fatal CHD in individuals with no prior history of CHD. A comprehensive and systematic review of the published scientific literature resulted in the identification of eight prospective studies (seven cohorts and one nested case-control study) that met predefined inclusion criteria. Relative to the consumption of<250mg n-3 LCFA per d, the consumption of≥250mg/d was associated with a significant 35·1% reduction in the risk of sudden cardiac death and a near-significant 16·6% reduction in the risk of total fatal coronary events, while the risk of non-fatal myocardial infarction was not significantly reduced. In several meta-analyses, which were based on US studies, risk of CHD death was found to be dose-dependently reduced by the n-3 LCFA, with further risk reductions observed with intakes in excess of 250mg/d. Prospective observational and intervention data from Japan, where intake of fish is very high, suggest that n-3 LCFA intakes of 900 to 1000mg/d and greater may confer protection against non-fatal myocardial infarction. Thus, the intake of 250mg n-3 LCFA per d may, indeed, be a minimum target to be achieved by the general population for the promotion of cardiovascular health.

CHD risk in relation to alcohol intake from categorical and open-ended dietary instruments

To examine the risk of CHD in relation to alcohol intake from three different instruments. In the European Prospective Investigation into Cancer in Norfolk study, weekly alcohol intake was estimated from a single question in a mail-in health and lifestyle questionnaire (HLQ), a semi-quantitative FFQ, and a 7 d diet diary (7DD). Information on smoking status, physical activity, disease history, social class and medication use was reported in the HLQ. Height, weight, blood pressure and blood lipids were measured at a health check-up. The average length of follow-up was 11 years. The association between alcohol intake and incident fatal and non-fatal CHD in a nested case-control sample was calculated using logistic regression. Norfolk, England. A total of 2151 cases of incident fatal and non-fatal CHD and 5354 controls. The Spearman correlation values between the 7DD, FFQ and HLQ alcohol estimates ranged from r = 0·70 to 0·82 (P < 0·0001 for all r values). Alcohol intake from all instruments was inversely associated with the risk of CHD in age- and multivariate-adjusted models. The relationships between the risk of CHD and alcohol intake from the 7DD, HLQ or FFQ were not significantly different from each other (P >0·10). A marginal difference between men and women was detected for the risk of CHD in relation to HLQ alcohol intake (P = 0·065). In conclusion, while the instruments were not uniform in their assessment of alcohol intake levels, the 7DD, HLQ and FFQ yielded similar inverse associations between alcohol intake and risk of CHD.

Reductions in incident coronary heart disease risk above guideline physical activity levels in men

Background One-half of Americans currently meet guideline physical activity levels. For these individuals, exceeding guideline levels may provide additional health benefits. Methods Incident physician-diagnosed myocardial infarction and angina, revascularization procedures (CABG, PTCA), and ischemic heart disease deaths during 7.7-year follow-up were compared to baseline usual distance run in 35,402 male runners. Results Men reported 467 incident CHD and the National Death Index identified an additional 54 ischemic heart disease deaths. Per km/day run, the men's risks declined 5% for fatal and nonfatal CHD ( P = 0.001), nonfatal CHD ( P = 0.0008), and revascularization procedures ( P = 0.002). Their risks for nonfatal myocardial infarctions and angina declined 7% ( P = 0.02) and 10% ( P = 0.003), respectively. Compared to <3 km/day run (upper limit guideline level), >9 km/day run produced risks 65% lower for angina ( P = 0.008), 29% lower for nonfatal CHD ( P = 0.04), and 26% lower for fatal and nonfatal CHD ( P = 0.06). Conclusions Exceeding guideline physical activity levels produce important CHD-risk reductions.