Diet, weight change, coronary heart disease and death : The Hordaland Health Studies

Background: While nutritional status is considered important in preventing coronary heart disease (CHD) and early mortality, there are numerous nutritional topics needing closer scrutiny. For example, it is unclear to what degree weight changes in older people are associated with mortality. Further, limiting intake of saturated fatty acids (SFA) often leads to increased intake of carbohydrates, and some types of carbohydrates have been shown to associate with increased risk of CHD. Further, studies suggest that cheese, a large contributor to SFA intake and vitamin K2 in the Nordic countries, associate with decreased risk of CHD. Objectives: 1) To study the association between weight change and mortality in older individuals; 2) To evaluate the importance of the interplay between SFA and total carbohydrates, including food sources, when evaluating the association between SFA and CHD, and 3) to evaluate the association between dietary vitamin K with CHD in middle-aged adults. Material and methods: Cohort study with participants from the Hordaland Health Study. In Paper I, 2935 men and women, age 71-74 years with weight measured both in 1992-93 and 1997-99 were followed for mortality through 2012. Multivariable Cox regression estimated Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing individuals who lost (≥5%) or gained (≥5%) weight to those with stable weight (±<5% weight change). Cox regression with penalized spline was also used to evaluate the association between weight change (in kg) and mortality. Analyses adjusted for age, sex, physical activity, smoking, diabetes mellitus, hypertension, and previous myocardial infarction or stroke. Papers II and III included 2995 and 2987 men and women, respectively, age 46-49 years at baseline in 1997-99. Participants were followed through 2009 to evaluate associations between intake of SFA, carbohydrates and vitamin K and incident CHD. Baseline diet was assessed by a past-year food frequency questionnaire. Energy- adjusted nutrient intakes were categorized into quartiles. Information on incident CHD events was obtained from the Cardiovascular Disease in Norway (CVDNOR) Project. Multivariable Cox regression estimated HRs and 95% CIs with test for linear trends across quartiles. Analyses were adjusted for age, sex, energy intake, physical activity, smoking and education. Cox regression with penalized spline was used to evaluate the associations between the dietary predictors and incident CHD. Results: Paper 1 In the adjusted analyses, participants who lost ≥5% weight had an increased mortality risk (HR 1.59; 95% CI 1.35, 1.89) compared to those with stable weight. In contrast, those with a weight gain of ≥5% had a similar risk of CHD as those with a stable weight (HR 1.07; 95% CI 0.90, 1.28). Penalized spline analyses, however, identified that those who lost more than three kg or gained more than 12 kg had increased mortality risk. Paper II In the adjusted analyses, SFA associated with lower risk of CHD (HRQuartile(Q)4vsQ1 0.ּ44; 95%CI 0.26, 0.76), p-trend 0.002). For carbohydrates, the opposite pattern was observed (HRQ4vsQ1 2.10; 95%CI 1.22, 3.63, p-trend 0.003). SFA from cheese associated with lower CHD risk (HRQ4vsQ1 0.44; 95%CI 0.24, 0.83, p-trend 0.006). A 5 energy percent (E%) substitution of carbohydrates with total fat, associated with lower CHD risk (HR 0.75; 95% CI 0.62, 0.90). Paper III In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HRQ4vsQ1 0.92; 95%CI 0.54, 1.57, p-trend 0.64), while there was a lower risk of CHD associated with higher intake of vitamin K2 (HRQ4vsQ1 0.52; 95% CI 0.29, 0.94, p-trend 0.03). Further adjustment for potential dietary confounders slightly attenuated the association for K2 (HRQ4vsQ1 0.58; 95% CI 0.28, 1.19). Conclusions and implications: Even a minor weight loss of ≥5% or >3 kg was associated with increased risk of mortality in older people, whereas a weight gain had to be more substantial to increase mortality risk. Thus, weight should be routinely monitored in older adults. A high intake of carbohydrates, reflecting low-fiber and relatively higher sucrose/fructose dietary sources, and a low intake of SFA were associated with higher CHD risk in the current study population. Substituting carbohydrates with total fat was associated with lower risk. Also, SFA from cheese was associated with lower risk of CHD. There is a need to clarify the relative health trade-offs between replacing carbohydrate intake with fat intake in study populations with diverse dietary habits and a wider range in carbohydrate and SFA intakes. In addition, results of our study suggest that dietary guidelines development and their communication to the public, especially regarding reductions in certain foods and nutrients need to consider the potential health impact of alternative sources of energy. A higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD. Current dietary guidelines are based on insufficient knowledge with regard to vitamin K metabolism and the different characteristics of K1 and K2. Therefore, our results indicate a need for more studies on the association between K2 and CHD. In addition, more knowledge about the absorption, transport and bioactivity of K2 is warranted.Doktorgradsavhandlin

Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study

Aims Hypertension has been suggested as a stronger risk factor for acute coronary syndromes (ACS) in women than men. Whether this also applies to stage 1 hypertension [blood pressure (BP) 130–139/80–89 mmHg] is not known. Methods and results We tested associations of stage 1 hypertension with ACS in 12 329 participants in the Hordaland Health Study (mean baseline age 41 years, 52% women). Participants were grouped by baseline BP category: Normotension (BP < 130/80 mmHg), stage 1 and stage 2 hypertension (BP ≥140/90 mmHg). ACS was defined as hospitalization or death due to myocardial infarction or unstable angina pectoris during 16 years of follow-up. At baseline, a lower proportion of women than men had stage 1 and 2 hypertension, respectively (25 vs. 35% and 14 vs. 31%, P < 0.001). During follow-up, 1.4% of women and 5.7% of men experienced incident ACS (P < 0.001). Adjusted for diabetes, smoking, body mass index, cholesterol, and physical activity, stage 1 hypertension was associated with higher risk of ACS in women [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.32–3.60], while the association was non-significant in men (HR 1.30, 95% CI 0.98–1.71). After additional adjustment for systolic and diastolic BP, respectively, stage 1 diastolic hypertension was associated with ACS in women (HR 2.79 [95% CI 1.62-4.82]), but not in men (HR 1.24 [95% CI 0.95-1.62]), while stage 1 systolic hypertension was not associated with ACS in either sex. Conclusion Among subjects in their early 40s, stage 1 hypertension was a stronger risk factor for ACS during midlife in women than in men.publishedVersio

Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort

Objective: The role of vitamin K in the regulation of vascular calcification is established. However, the association of dietary vitamins K1 and K2 with risk of coronary heart disease (CHD) is inconclusive. Design: Prospective cohort study. Setting: We followed participants in the community-based Hordaland Health Study from 1997 - 1999 through 2009 to evaluate associations between intake of vitamin K and incident (new onset) CHD. Baseline diet was assessed by a past-year food frequency questionnaire. Energy-adjusted residuals of vitamin K1 and vitamin K2 intakes were categorised into quartiles. Participants: 2987 Norwegian men and women, age 46–49 years. Methods: Information on incident CHD events was obtained from the nationwide Cardiovascular Disease in Norway (CVDNOR) Project. Multivariable Cox regression estimated HRs and 95% CIs with test for linear trends across quartiles. Analyses were adjusted for age, sex, total energy intake, physical activity, smoking and education. A third model further adjusted K1 intake for energy-adjusted fibre and folate, while K2 intake was adjusted for energy-adjusted saturated fatty acids and calcium. Results: During a median follow-up time of 11 years, we documented 112 incident CHD cases. In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HRQ4vsQ1 = 0.92 (95% CI 0.54 to 1.57), p for trend 0.64), while there was a lower risk of CHD associated with higher intake of energy-adjusted vitamin K2 (HRQ4vsQ1 = 0.52 (0.29 to 0.94), p for trend 0.03). Further adjustment for potential dietary confounders did not materially change the association for K1, while the association for K2 was slightly attenuated (HRQ4vsQ1 = 0.58 (0.28 to 1.19)). Conclusions: A higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD.publishedVersio

The Association of Meat Intake With All-Cause Mortality and Acute Myocardial Infarction Is Age-Dependent in Patients With Stable Angina Pectoris

Background: Red and processed meat intake have been associated with increased risk of morbidity and mortality, and a restricted intake is encouraged in patients with cardiovascular disease. However, evidence on the association between total meat intake and clinical outcomes in this patient group is lacking. Objectives: To investigate the association between total meat intake and risk of all-cause mortality, acute myocardial infarction, cancer, and gastrointestinal cancer in patients with stable angina pectoris. We also investigated whether age modified these associations. Materials and Methods: This prospective cohort study consisted of 1,929 patients (80% male, mean age 62 years) with stable angina pectoris from the Western Norway B-Vitamin Intervention Trial. Dietary assessment was performed by the administration of a semi-quantitative food frequency questionnaire. Cox proportional hazards models were used to investigate the association between a relative increase in total meat intake and the outcomes of interest. Results: The association per 50 g/1,000 kcal higher intake of total meat with morbidity and mortality were generally inconclusive but indicated an increased risk of acute myocardial infarction [HR: 1.26 (95% CI: 0.98, 1.61)] and gastrointestinal cancer [1.23 (0.70, 2.16)]. However, we observed a clear effect modification by age, where total meat intake was associated with an increased risk of mortality and acute myocardial infarction among younger individuals, but an attenuation, and even reversal of the risk association with increasing age. Conclusion: Our findings support the current dietary guidelines emphasizing a restricted meat intake in cardiovascular disease patients but highlights the need for further research on the association between meat intake and health outcomes in elderly populations. Future studies should investigate different types of meat separately in other CVD-cohorts, in different age-groups, as well as in the general population.publishedVersio

Inflammation, sex, blood pressure changes and hypertension in midlife: the Hordaland Health Study

Our aim was to test sex-specific associations of circulating markers of inflammation with blood pressure (BP) and incident hypertension in midlife. Participants in the Hordaland Health study (n = 3280, 56% women, mean age 48 years) were examined at baseline and followed for 6 years. Circulating levels of inflammatory markers including high-sensitive C-reactive protein (hs-CRP), neopterin, and pyridoxic acid ratio (PAr) index were measured at follow-up. The associations with systolic/diastolic BP and incident hypertension were tested in sex-specific linear- or logistic-regression analyses adjusted for body mass index, serum triglycerides, creatinine, physical activity, smoking and diabetes. At follow-up, women had lower mean BP than men (124/72 vs. 130/78 mmHg, p < 0.001). Higher hs-CRP was significantly associated with greater systolic and diastolic BP (standardized β = 0.07 and β = 0.09, both p < 0.01) in women, but not in men. Higher neopterin was associated with higher diastolic BP in women and higher PAr index was associated with higher diastolic BP in women and higher systolic and diastolic BP in men (all p < 0.01). Compared to hs-CRP < 1 mg/l, higher levels of hs-CRP 1–<3 mg/l and hs-CRP ≥ 3 mg/l were associated with new-onset hypertension only in women (odds ratio (OR) 1.74, 95% CI 1.20–2.53 and OR 1.87, 95% CI 1.20–2.90). Sex-interactions were found for hs-CRP and neopterin in models on incident hypertension and diastolic BP, respectively (both p < 0.05). Higher levels of circulating markers of inflammation were associated with higher BP and incident hypertension in a sex-specific manner. Our results suggest a sex-specific interaction between cardiovascular inflammation and BP in midlife.publishedVersio

Diet, weight change, coronary heart disease and death : The Hordaland Health Studies

Background: While nutritional status is considered important in preventing coronary heart disease (CHD) and early mortality, there are numerous nutritional topics needing closer scrutiny. For example, it is unclear to what degree weight changes in older people are associated with mortality. Further, limiting intake of saturated fatty acids (SFA) often leads to increased intake of carbohydrates, and some types of carbohydrates have been shown to associate with increased risk of CHD. Further, studies suggest that cheese, a large contributor to SFA intake and vitamin K2 in the Nordic countries, associate with decreased risk of CHD. Objectives: 1) To study the association between weight change and mortality in older individuals; 2) To evaluate the importance of the interplay between SFA and total carbohydrates, including food sources, when evaluating the association between SFA and CHD, and 3) to evaluate the association between dietary vitamin K with CHD in middle-aged adults. Material and methods: Cohort study with participants from the Hordaland Health Study. In Paper I, 2935 men and women, age 71-74 years with weight measured both in 1992-93 and 1997-99 were followed for mortality through 2012. Multivariable Cox regression estimated Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing individuals who lost (≥5%) or gained (≥5%) weight to those with stable weight (±<5% weight change). Cox regression with penalized spline was also used to evaluate the association between weight change (in kg) and mortality. Analyses adjusted for age, sex, physical activity, smoking, diabetes mellitus, hypertension, and previous myocardial infarction or stroke. Papers II and III included 2995 and 2987 men and women, respectively, age 46-49 years at baseline in 1997-99. Participants were followed through 2009 to evaluate associations between intake of SFA, carbohydrates and vitamin K and incident CHD. Baseline diet was assessed by a past-year food frequency questionnaire. Energy- adjusted nutrient intakes were categorized into quartiles. Information on incident CHD events was obtained from the Cardiovascular Disease in Norway (CVDNOR) Project. Multivariable Cox regression estimated HRs and 95% CIs with test for linear trends across quartiles. Analyses were adjusted for age, sex, energy intake, physical activity, smoking and education. Cox regression with penalized spline was used to evaluate the associations between the dietary predictors and incident CHD. Results: Paper 1 In the adjusted analyses, participants who lost ≥5% weight had an increased mortality risk (HR 1.59; 95% CI 1.35, 1.89) compared to those with stable weight. In contrast, those with a weight gain of ≥5% had a similar risk of CHD as those with a stable weight (HR 1.07; 95% CI 0.90, 1.28). Penalized spline analyses, however, identified that those who lost more than three kg or gained more than 12 kg had increased mortality risk. Paper II In the adjusted analyses, SFA associated with lower risk of CHD (HRQuartile(Q)4vsQ1 0.ּ44; 95%CI 0.26, 0.76), p-trend 0.002). For carbohydrates, the opposite pattern was observed (HRQ4vsQ1 2.10; 95%CI 1.22, 3.63, p-trend 0.003). SFA from cheese associated with lower CHD risk (HRQ4vsQ1 0.44; 95%CI 0.24, 0.83, p-trend 0.006). A 5 energy percent (E%) substitution of carbohydrates with total fat, associated with lower CHD risk (HR 0.75; 95% CI 0.62, 0.90). Paper III In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HRQ4vsQ1 0.92; 95%CI 0.54, 1.57, p-trend 0.64), while there was a lower risk of CHD associated with higher intake of vitamin K2 (HRQ4vsQ1 0.52; 95% CI 0.29, 0.94, p-trend 0.03). Further adjustment for potential dietary confounders slightly attenuated the association for K2 (HRQ4vsQ1 0.58; 95% CI 0.28, 1.19). Conclusions and implications: Even a minor weight loss of ≥5% or >3 kg was associated with increased risk of mortality in older people, whereas a weight gain had to be more substantial to increase mortality risk. Thus, weight should be routinely monitored in older adults. A high intake of carbohydrates, reflecting low-fiber and relatively higher sucrose/fructose dietary sources, and a low intake of SFA were associated with higher CHD risk in the current study population. Substituting carbohydrates with total fat was associated with lower risk. Also, SFA from cheese was associated with lower risk of CHD. There is a need to clarify the relative health trade-offs between replacing carbohydrate intake with fat intake in study populations with diverse dietary habits and a wider range in carbohydrate and SFA intakes. In addition, results of our study suggest that dietary guidelines development and their communication to the public, especially regarding reductions in certain foods and nutrients need to consider the potential health impact of alternative sources of energy. A higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD. Current dietary guidelines are based on insufficient knowledge with regard to vitamin K metabolism and the different characteristics of K1 and K2. Therefore, our results indicate a need for more studies on the association between K2 and CHD. In addition, more knowledge about the absorption, transport and bioactivity of K2 is warranted

Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study

Aims Hypertension has been suggested as a stronger risk factor for acute coronary syndromes (ACS) in women than men. Whether this also applies to stage 1 hypertension [blood pressure (BP) 130–139/80–89 mmHg] is not known. Methods and results We tested associations of stage 1 hypertension with ACS in 12 329 participants in the Hordaland Health Study (mean baseline age 41 years, 52% women). Participants were grouped by baseline BP category: Normotension (BP < 130/80 mmHg), stage 1 and stage 2 hypertension (BP ≥140/90 mmHg). ACS was defined as hospitalization or death due to myocardial infarction or unstable angina pectoris during 16 years of follow-up. At baseline, a lower proportion of women than men had stage 1 and 2 hypertension, respectively (25 vs. 35% and 14 vs. 31%, P < 0.001). During follow-up, 1.4% of women and 5.7% of men experienced incident ACS (P < 0.001). Adjusted for diabetes, smoking, body mass index, cholesterol, and physical activity, stage 1 hypertension was associated with higher risk of ACS in women [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.32–3.60], while the association was non-significant in men (HR 1.30, 95% CI 0.98–1.71). After additional adjustment for systolic and diastolic BP, respectively, stage 1 diastolic hypertension was associated with ACS in women (HR 2.79 [95% CI 1.62-4.82]), but not in men (HR 1.24 [95% CI 0.95-1.62]), while stage 1 systolic hypertension was not associated with ACS in either sex. Conclusion Among subjects in their early 40s, stage 1 hypertension was a stronger risk factor for ACS during midlife in women than in men

Factors associated with increase in blood pressure and incident hypertension in early midlife: the Hordaland Health Study

Purpose: We aimed to identify sex-specific factors associated with increase in blood pressure (BP) and incident hypertension in early midlife. Materials and methods: 2,008 women and 1,610 men aged 40-43 years were followed for six years in the Hordaland Health Study. Participants taking antihypertensive medication at baseline were excluded. High-normal BP was defined as baseline BP 130-139/85-89 mmHg, and incident hypertension as BP≥140/90 mmHg or use of antihypertensive medication at follow-up. Results: During follow-up, an increase in systolic (SBP) and diastolic (DBP) BP was observed in 54% and 30% of women vs. 44% and 41% of men, respectively (both p<0.001). In both sexes higher baseline body mass index (BMI) and increases in BMI and serum lipids were associated with increases in SBP and DBP during follow-up (all p<0.05). Incident hypertension was more common in men (14 vs.11%, p<0.01), and predicted by higher BMI and high-normal BP at baseline in both sexes, and by higher serum triglyceride level in women (all p<0.01). Conclusion: In the Hordaland Health Study, BP development differed between women and men in early midlife. The main factors associated with BP increase in both sexes were higher BMI, weight gain and increases in serum lipids

Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort

Objective: The role of vitamin K in the regulation of vascular calcification is established. However, the association of dietary vitamins K1 and K2 with risk of coronary heart disease (CHD) is inconclusive. Design: Prospective cohort study. Setting: We followed participants in the community-based Hordaland Health Study from 1997 - 1999 through 2009 to evaluate associations between intake of vitamin K and incident (new onset) CHD. Baseline diet was assessed by a past-year food frequency questionnaire. Energy-adjusted residuals of vitamin K1 and vitamin K2 intakes were categorised into quartiles. Participants: 2987 Norwegian men and women, age 46–49 years. Methods: Information on incident CHD events was obtained from the nationwide Cardiovascular Disease in Norway (CVDNOR) Project. Multivariable Cox regression estimated HRs and 95% CIs with test for linear trends across quartiles. Analyses were adjusted for age, sex, total energy intake, physical activity, smoking and education. A third model further adjusted K1 intake for energy-adjusted fibre and folate, while K2 intake was adjusted for energy-adjusted saturated fatty acids and calcium. Results: During a median follow-up time of 11 years, we documented 112 incident CHD cases. In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HRQ4vsQ1 = 0.92 (95% CI 0.54 to 1.57), p for trend 0.64), while there was a lower risk of CHD associated with higher intake of energy-adjusted vitamin K2 (HRQ4vsQ1 = 0.52 (0.29 to 0.94), p for trend 0.03). Further adjustment for potential dietary confounders did not materially change the association for K1, while the association for K2 was slightly attenuated (HRQ4vsQ1 = 0.58 (0.28 to 1.19)). Conclusions: A higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD

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

Objective: 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. Design: Prospective cohort study. Setting: 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). Participants: 2995 men and women, aged 46–49 years. Results: 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). Conclusions: 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