Time-dependent trends in cardiovascular adverse events during follow-up after carotid or iliofemoral endarterectomy.

BACKGROUND: Recent observations have suggested a decline in vulnerable carotid artery and iliofemoral atherosclerotic plaque characteristics over the past decade. The aim of this study was to determine whether, in the presence of clinically manifest carotid or peripheral artery disease, secondary adverse cardiovascular events decreased over this period. METHODS: Patients included in the Athero-Express biobank between 2003 and 2012 were analysed. During 3-year follow-up, composite cardiovascular endpoints were documented yearly, including: myocardial infarction, coronary interventions, stroke, peripheral interventions and cardiovascular death. The major cardiovascular endpoint consisted of myocardial infarction, stroke and cardiovascular death. RESULTS: Some 1684 patients who underwent carotid endarterectomy (CEA) and another 530 who had iliofemoral endarterectomy (IFE) were analysed. In total, 405 (25·2 per cent) and 236 (45·9 per cent) patients had a composite cardiovascular endpoint within 3 years after CEA and IFE respectively. Corrected for possible confounders, the percentage of patients with a secondary cardiovascular event after CEA did not change over time (hazard ratio (HR) 0·91, 95 per cent c.i. 0·65 to 1·28; P = 0·590, for 2011-2012 versus 2003-2004). In patients who had IFE, the incidence of secondary cardiovascular events significantly decreased only in the last 2 years (HR 0·62, 0·41 to 0·94; P = 0·024), owing to a decrease in peripheral (re)interventions in 2011-2012 (HR 0·59, 0·37 to 0·94; P = 0·028). No decrease in major cardiovascular events was observed in either group. CONCLUSION: In patients who had undergone either CEA or IFE there was no evidence of a decrease in all secondary cardiovascular events. There were no differences in major cardiovascular events.

Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study.

AIMS/HYPOTHESIS: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption. RESULTS: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants. CONCLUSIONS/INTERPRETATION: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.

The relationship between energy intake and body-growth in children with cystic fibrosis.

BACKGROUND & AIMS: Body-growth, expressed as weight- and height gain, is a strong predictor of morbidity and mortality in patients with cystic fibrosis (CF). Whether current historically based recommendations on a high-energy diet are sufficient for optimal growth is questionable. We therefore assessed the longitudinal relation between body-growth and routine energy intake in paediatric CF patients. METHODS: Included were patients with CF, aged 2-10 years of whom we obtained 969 measurements of weight and height along with dietary records, and 786 coefficient of fat absorption measurements (CFA). We described body-growth, energy intake, macronutrient intake and the long-term effect of energy intake and coefficient of fat absorption on body-growth during the 8-year follow-up period. RESULTS: Enrolled were 191 children with CF who had a compromised growth when compared to healthy children. The dietary intake was ≥110% estimated average requirement (EAR) in 47% of the measurements (457/969) and did not (fully) achieve the recommended high-energy level (110-200% EAR). Further, the intake expressed as EAR decreased with increasing age. Cross-sectionally, boys and girls with higher caloric intakes had higher weight-for-age (WFA). The caloric intake explained 18 and 6% of the variation. Further, boys with higher caloric intakes had also higher height-for-age-adjusted-for-target-height (HFA/TH) or BMI. The caloric intake explained 6 or 7% of the variation. Longitudinally, caloric intake was associated with both WFA in boys and girls, and with BMI in boys. Each 100 calories increased intake would result in a 0.01 (girls)-0.02 increase in z-score WFA and 0.03 increase in z-score BMI. We found no significant association between CFA and WFA, HFA/TH or BMI. The contribution of protein, fat and carbohydrates was not associated with WFA, nor with HFA/TH or BMI. CONCLUSION: Even at this relatively early age, a compromised growth in children with CF was found when compared to healthy children. The energy intake was below 110% EAR in 47% of the measurements, and appeared to be insufficient to prevent suboptimal body-growth over the 8-years of follow-up.

Excess early postnatal weight gain and blood pressure in healthy young children.

Blood pressure (BP) tracks from childhood to adulthood, and early BP trajectories predict cardiovascular disease risk later in life. Excess postnatal weight gain is associated with vascular changes early in life. However, to what extent it is associated with children's BP is largely unknown. In 853 healthy 5-year-old children of the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort, systolic (SBP) and diastolic BP (DBP) were measured, and z scores of individual weight gain rates adjusted for length gain rates were calculated using at least two weight and length measurements from birth until 3 months of age. Linear regression analyses were conducted to investigate the association between weight gain rates adjusted for length gain rates and BP adjusted for sex and ethnicity. Each standard deviation increase in weight gain rates adjusted for length gain rates was associated with 0.9 mmHg (95% CI 0.3, 1.5) higher sitting SBP after adjustment for confounders. Particularly in children in the lowest birth size decile, high excess weight gain was associated with higher sitting SBP values compared to children with low weight gain rates adjusted for length gain rates. BMI and visceral adipose tissue partly explained the association between excess weight gain and sitting SBP (ß 0.5 mmHg, 95% CI -0.3, 1.3). Weight gain rates adjusted for length gain rates were not associated with supine SBP or DBP. Children with excess weight gain, properly adjusted for length gain, in the first three months of life, particularly those with a small birth size, showed higher sitting systolic BP at the age of 5 years.

Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women.

OBJECTIVE: To investigate the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD). DESIGN: Prospective cohort study. SUBJECTS: A total of 16 165 women aged 49-70 years without prior CVD. SUBJECTS were breast cancer screening participants in the PROSPECT-EPIC cohort, which is 1 of the 2 Dutch contributions to the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Each participant completed a validated food frequency questionnaire. Folate intake was calculated with the Dutch National Food Database. Betaine and choline intakes were calculated with the USDA database containing choline and betaine contents of common US foods. Data on coronary heart disease (CHD) events and cerebrovascular accident (CVA) events morbidity data were obtained from the Dutch Centre for Health Care Information. RESULTS: During a median follow-up period of 97 months, 717 women were diagnosed with CVD. After adjustment, neither folate, nor betaine, nor choline intakes were associated with CVD (hazard ratios for highest versus lowest quartile were 1.23 (95% confidence interval 0.75; 2.01), 0.90 (0.69; 1.17), 1.04 (0.71; 1.53), respectively). In a subsample of the population, high folate and choline intakes were statistically significantly associated with lower homocysteine levels. High betaine intake was associated with slightly lower high-density lipoprotein (HDL)-cholesterol concentrations. CONCLUSION: Regular dietary intakes of folate, betaine and choline were not associated with CVD risk in post-menopausal Dutch women. However, the effect of doses of betaine and choline beyond regular dietary intake--for example, via supplementation or fortification--remains unknown.

Reproducibility and relative validity of a food frequency questionnaire to estimate intake of dietary phylloquinone and menaquinones.

BACKGROUND/OBJECTIVES: This study aims to investigate the reproducibility and relative validity of the Dutch food frequency questionnaire (FFQ), to estimate intake of dietary phylloquinone and menaquinones compared with 24-h dietary recalls (24HDRs) and plasma markers of vitamin K status. SUBJECTS/METHODS: In a cross-sectional study among 63 men and 58 women, the FFQ was completed three times over a 1-year period and the reproducibility was calculated over these measurements. Twelve-monthly 24HDR were collected to estimate relative validity. In addition, the relative validity of the FFQ, compared with plasma phylloquinone and desphospho-uncarboxylated matrix Gla protein (dpucMGP), was assessed cross-sectionally among 507 postmenopausal women. RESULTS: Intraclass correlations showed a good reproducibility, with correlations ranging from 0.65 to 0.83. The relative validity for phylloquinone intake compared with 24HDR was lower for women (rs=0.28) than men (rs=0.40). The relative validity, compared with 24HDR, for intake of short-chain menaquinones were ranging between 0.30 and 0.34. Long-chain menaquinones showed good relative validity (rs=0.60-0.69). Plasma phylloquinone concentrations were weakly correlated with phylloquinone intake (rs=0.16 (0.07-0.24). Plasma dpucMGP was negatively but weakly correlated with phylloquinone intake (rs=-0.09 (-0.18; -0.01)) and long-chain menaquinones (rs=-0.13 (-0.21; -0.04)), but not with short-chain menaquinones (rs=-0.04 (-0.13; 0.05)). CONCLUSIONS: The FFQ is reproducible to rank subjects for phylloquinone and menaquinone intake.The relative validity of our FFQ, compared with 24HDR, to estimate intake of phylloquinone and short-chain menaquinones was low, but the relative validity for long-chain menaquinones was good. The relative validity of our FFQ, compared with plasma phylloquinone and dpucMGP, was relatively low for both phylloquinone and menaquinone intake.

Circulating desphospho-uncarboxylated matrix γ-carboxyglutamate protein and the risk of coronary heart disease and stroke.

BACKGROUND: High vitamin K intake is associated with a reduced risk of coronary heart disease (CHD). This is thought to be mediated by increased activation of the vitamin K-dependent matrix γ-carboxyglutamate protein (MGP). Desphospho-uncarboxylated MGP (dp-ucMGP) is associated with both vitamin K status and vascular calcification. However, the association of dp-ucMGP with CHD and stroke in the general population has not been investigated to date. OBJECTIVE: To investigate the association of dp-ucMGP with incident CHD or stroke. METHODS: A prospective case-cohort study with a representative baseline sample of 1406 participants and 1154 and 380 incident cases of CHD and stroke, respectively, was nested within the EPIC-NL study. Circulating dp-ucMGP levels were measured with ELISA in baseline plasma samples. The incidence rates of fatal and non-fatal CHD and stroke were obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs) per standard deviation (SD) and per quartile of circulating dp-ucMGP levels. RESULTS AND CONCLUSION: The average follow-up was 11.5 years. Levels of dp-ucMGP were not associated with CHD risk, with an HR per SD of 1.00 (95% confidence interval [CI] 0.93-1.07) and an HRQ4 vs. Q1 of 0.94 (95% CI 0.79-1.13) after adjustment for cardiovascular risk factors. There was no association of dp-ucMGP stroke risk (HRSD  0.98, 95% CI 0.90-1.08; and HRQ4 vs. Q1  1.09, 95% CI 0.78-1.51). This study could not confirm that high dp-ucMGP levels, reflecting poor vitamin K status, are associated with increased CHD or stroke risk in the general population.

The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein.

OBJECTIVE: To investigate whether menaquinone-7 (MK-7) supplementation increases carboxylation of MGP. DESIGN: A randomized, double-blind, placebo-controlled trial was performed. Sixty participants (40-65 y) were randomly allocated to supplementation of 180 µg/d, 360 µg/d of MK-7 or placebo during 12 weeks. At baseline, after 4 and 12 weeks, desphospho-uncarboxylated MGP (dp-ucMGP), desphospho-carboxylated MGP (dp-cMGP) and total uncarboxylated MGP (t-ucMGP) were measured by ELISA techniques. Furthermore, the ratio of uncarboxylated osteocalcin (ucOC) to carboxylated osteocalcin (cOC) was used as proxy of vitamin K status and various cardiovascular risk factors were measured. RESULTS: Dp-ucMGP decreased significantly and dose-dependently in the 180 µg and 360 µg MK-7 supplementation groups (P time*treatment < 0.001) after 12 weeks, by 31% and 46% respectively, while dp-ucMGP levels remained unchanged after placebo treatment. The osteocalcin ratio also decreased significantly after 12-week supplementation with 180 µg (60%) and 360 µg (74%) MK-7 (P time*treatment < 0.001), while levels remained unchanged after placebo treatment. These results indicate improved vitamin K status and good compliance to the study treatment. Changes over time of dp-cMGP (p = 0.42) and t-ucMGP (p = 0.23) levels did not differ between treatment arms. Other cardiovascular risk factors did not differ between treatments arms. CONCLUSIONS: Menaquinone supplementation dose-dependently decreases dp-ucMGP concentrations, but does not affect other MGP species. Dp-ucMGP may serve as a non-invasive marker of vitamin K status.