AimsGenetic risk scores (GRSs) have been associated with coronary heart disease (CHD) in large studies. We asked whether expanding an established 27-variant GRS (GRS27) to a 50-variant GRS (GRS50) improved CHD prediction and whether GRSs are independent of self-reported family history of CHD.Methods and resultsThe association between GRSs and incident CHD was assessed in Cox models adjusting for established risk factors in 23 595 participants of the Malmö Diet and Cancer study—a prospective, population-based study. During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. After adjustment for established risk factors, both GRS27 and GRS50 were associated with incident CHD [hazard ratio (HR) = 1.70 for high (top quintile) vs. low (bottom quintile) of GRS27; 95% confidence interval (CI): 1.48–1.94; Ptrend = 1.6 × 10−15 and HR = 1.92 for GRS50; 95% CI: 1.67–2.20; Ptrend = 6.2 × 10−22]. Adding 23 single nucleotide polymorphisms (SNPs) to GRS27 improved risk prediction (P = 3 × 10−6). Further adjustment for self-reported family history did not appreciably change the risk estimates of either GRS27 (HR = 1.65; 95% CI: 1.45–1.89) or GRS50 (HR = 1.87; 95% CI: 1.63–2.14). The addition of GRS50 to established risk factors, including self-reported family history, improved discrimination (P < 0.0001) and reclassification (continuous net reclassification improvement index = 0.17, P < 0.0001). In young participants (below median age), those with high GRS50 had 2.4-fold greater risk (95% CI: 1.85–3.12) than those with low GRS50.ConclusionThe addition of 23 SNPs to an existing GRS27 improved CHD risk prediction and was independent of self-reported family history. Coronary heart disease risk assessment by GRS could be particularly useful in young individuals.

OBJECTIVE The 2019 Standards of Medical Care in Diabetes suggested that patients with nonalcoholic fatty liver disease (NAFLD) should be evaluated for liver fibrosis. However, the performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and advanced fibrosis has not been carefully assessed in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS In this cross-sectional study, patients (n = 213) had a liver MRS, and those with a diagnosis of NAFLD underwent a percutaneous liver biopsy. Several noninvasive clinical models/scores and plasma biomarkers were measured to identify NASH and advanced fibrosis (NASH: ALT, cytokeratin-18, NashTest 2, HAIR, BARD, and OWLiver; advanced fibrosis: AST, fragments of propeptide of type III procollagen [PRO-C3], FIB-4, APRI, NAFLD fibrosis score, and FibroTest). RESULTS None of the noninvasive tools assessed for the diagnosis of NASH in patients with T2DM had an optimum performance (all areas under the curve [AUCs] &lt;0.80). Of note, none of the panels or biomarkers was able to outperform plasma ALT (AUC 0.78 [95% CI 0.71–0.84]). Performance was better to diagnose advanced fibrosis, in which plasma PRO-C3, AST, and APRI showed better results than the other approaches (AUC 0.90 [0.85–0.95], 0.85 [0.80–0.91], and 0.86 [0.80–0.91], respectively). Again, none of the approaches did significantly better than plasma AST. Sequential use of plasma AST and other noninvasive tests may help in limiting the number of liver biopsies required to identify patients with advanced fibrosis. CONCLUSIONS Performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of NASH or advanced fibrosis was suboptimal in patients with T2DM. Combination of multiple tests may provide an alternative to minimize the need for liver biopsies to detect fibrosis in these patients.

In both the CARE and the WOSCOPS trials, carriers of the KIF6 719Arg allele had an increased risk of coronary events, and pravastatin treatment substantially reduced that risk.

Background While genetic variation at chromosome 9p21.3 is associated with incident cardiovascular disease (CVD), it is unclear whether screening for this polymorphism improves risk prediction. Objective To determine whether knowledge of variation at chromosome 9p21.3 provides predictive information beyond that from other readily available risk factors. Design Prospective cohort study Setting United States Patients 22,129 female Caucasian health professionals participating in the Women's Genome Health Study, initially free of any major chronic disease, who were prospectively followed over a median of 10.2 years for incident CVD. Measurements Polymorphism at rs10757274 in chromosome 9p21.3 and additional CVD risk factors (blood pressure, smoking status, diabetes, blood levels of cholesterol, high-sensitivity C-reactive protein, and family history of premature myocardial infarction). Results Polymorphism at rs10757274 was associated with an adjusted hazard ratio for incident CVD of 1.25 (95% CI 1.04 − 1.51) for the AG genotype and 1.32 (95% CI 1.07 − 1.63) for the GG genotype. However, the addition of the genotype to a prediction model based on traditional risk factors, high-sensitivity C-reactive protein and family history of premature myocardial infarction had no effect on model discrimination as measured by the c-index (0.807 to 0.809) nor showed improvement of the Net Reclassification Improvement (−0.2%, p=0.59) or the Integrated Discrimination Improvement (0.0, p=0.18). Limitations Results are limited to Caucasian women. Conclusions In this large prospective cohort of Caucasian women, genetic variation in chromosome 9p21.3 was associated with incident CVD but did not improve on the discrimination or classification of predicted risk achieved with traditional risk factors, high-sensitivity C-reactive protein and family history of premature myocardial infarction.

The epidemiological evidence for an obesity-cancer association is solid, whereas the association between obesity-associated lipoprotein levels and cancer is less evident. We investigated circulating levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) and association to risk of overall cancer and common cancer forms. The Malm€ o Diet and Cancer Study, a population-based prospective cohort study, enrolled 17,035 women and 11,063 men (1991)(1992)(1993)(1994)(1995)(1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow-up, January 1, 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort and HDL-C and LDL-C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HR adj ApoA1 5 0.98, 95%CI: 0.95,1.01; HR adj ApoB 5 1.01, 95%CI: 0.98-1.04). Among men, ApoB was positively associated with cancer risk (HR adj ApoB 5 1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HR adj 5 0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HR adj 5 0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HR adj 5 1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HR adj 5 1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer.Cancer incidence has increased continuously over time forcing action to be taken at all stages of prevention. 1 In particular, improved primary prevention of cancer requires identification of risk markers, preferentially in drug and lifestyle modifiable systems. 1,2 Within the field of cardiovascular disease (CVD), development of risk markers has been